Vezzoli Dott.ssa Alessandra

Pubblicazioni su PubMed

• Dopamine/BDNF loss underscores narcosis cognitive impairment in divers: a proof of concept in a dry condition.
  Eur J Appl Physiol

  2022 Oct;():. doi: 10.1007/s00421-022-05055-6.
  
  Bosco Gerardo, Giacon Tommaso Antonio, Paolocci Nazareno, Vezzoli Alessandra, Noce Cinzia Della, Paganini Matteo, Agrimi Jacopo, Garetto Giacomo, Cialoni Danilo, D'Alessandro Natalie, Camporesi Enrico M, Mrakic-Sposta Simona
  
  Abstract
  
  PURPOSE:
  Divers can experience cognitive impairment due to inert gas narcosis (IGN) at depth. Brain-derived neurotrophic factor (BDNF) rules neuronal connectivity/metabolism to maintain cognitive function and protect tissues against oxidative stress (OxS). Dopamine and glutamate enhance BDNF bioavailability. Thus, we hypothesized that lower circulating BDNF levels (via lessened dopamine and/or glutamate release) underpin IGN in divers, while testing if BDNF loss is associated with increased OxS.
  
  METHODS:
  To mimic IGN, we administered a deep narcosis test via a dry dive test (DDT) at 48 msw in a multiplace hyperbaric chamber to six well-trained divers. We collected: (1) saliva samples before DDT (T0), 25 msw (descending, T1), 48 msw (depth, T2), 25 msw (ascending, T3), 10 min after decompression (T4) to dopamine and/or reactive oxygen species (ROS) levels; (2) blood and urine samples at T0 and T4 for OxS too. We administered cognitive tests at T0, T2, and re-evaluated the divers at T4.
  
  RESULTS:
  At 48 msw, all subjects experienced IGN, as revealed by the cognitive test failure. Dopamine and total antioxidant capacity (TAC) reached a nadir at T2 when ROS emission was maximal. At decompression (T4), a marked drop of BDNF/glutamate content was evidenced, coinciding with a persisting decline in dopamine and cognitive capacity.
  
  CONCLUSIONS:
  Divers encounter IGN at - 48 msw, exhibiting a marked loss in circulating dopamine levels, likely accounting for BDNF-dependent impairment of mental capacity and heightened OxS. The decline in dopamine and BDNF appears to persist at decompression; thus, boosting dopamine/BDNF signaling via pharmacological or other intervention types might attenuate IGN in deep dives.
  
  © 2022. The Author(s).
  
  Guarda su PubMed

• Smell Impairment in Stage I-II Obesity: Correlation with Biochemical Regulators and Clinical Aspects.
  Laryngoscope

  2022 Oct;132(10):2028-2035. doi: 10.1002/lary.30325.
  
  Micarelli Alessandro, Mrakic-Sposta Simona, Micarelli Beatrice, Malacrida Sandro, Misici Ilaria, Carbini Valentina, Iennaco Ilaria, Caputo Sara, Vezzoli Alessandra, Alessandrini Marco
  
  Abstract
  
  OBJECTIVE:
  To evaluate the differences in olfactory sensitivity, nutritional habits, levels of modulators of feeding and smell, bioelectrical impedance analysis (BIA) measures and metabolic assays between two groups of participants with stage I and II obesity and reciprocal relationships between these parameters.
  
  METHODS:
  Eighteen participants with stage I (11 female; mean age = 54.3?±?13.1?years) and 20 participants with stage II (10 female; mean age = 54.5?±?11.9) obesity underwent a food frequency questionnaire and Sniffin' Sticks® test battery, anthropometric parameters, and BIA measurements as well as metabolic assays (including plasma levels of leptin, insulin, ghrelin, glucose, insulin-like growth factor-1 [IGF-1] and usual laboratory parameters).
  
  RESULTS:
  The stage II obesity participants demonstrated significant higher levels of insulin and leptin and lower levels of ghrelin and IGF-1, a reduction in odor identification (OI) and in total olfactory score, and an increase in visceral and total fat percentage. Among a mosaic of multiple correlations, ghrelin was found to positively correlate with OI and leptin negatively with odor discrimination.
  
  CONCLUSION:
  The present study expands the notions positing the olfactory perception - and its connections with metabolic cues, foods habits and BIA measures - changes across the two most important obesity stages. This could ameliorate clinical and research deepening of obesity-related olfactory behavior with possible consequences on diagnosis, treatment and prevention of onset and development of obesity, thus opening possible future strategies involving multidisciplinary contributions.
  
  LEVEL OF EVIDENCE:
  3 Laryngoscope, 132:2028-2035, 2022.
  
  © 2022 The American Laryngological, Rhinological and Otological Society, Inc.
  
  Guarda su PubMed

• Lifespan and ROS levels in different Drosophila melanogaster strains after 24?h hypoxia exposure.
  Biol Open

  2022 Jun;11(6):. doi: bio059386.
  
  Malacrida Sandro, De Lazzari Federica, Mrakic-Sposta Simona, Vezzoli Alessandra, Zordan Mauro A, Bisaglia Marco, Menti Giulio Maria, Meda Nicola, Frighetto Giovanni, Bosco Gerardo, Dal Cappello Tomas, Strapazzon Giacomo, Reggiani Carlo, Gussoni Maristella, Megighian Aram
  
  Abstract
  
  During recent decades, model organisms such as Drosophila melanogaster have made it possible to study the effects of different environmental oxygen conditions on lifespan and oxidative stress. However, many studies have often yielded controversial results usually assigned to variations in Drosophila genetic background and differences in study design. In this study, we compared longevity and ROS levels in young, unmated males of three laboratory wild-type lines (Canton-S, Oregon-R and Berlin-K) and one mutant line (Sod1n1) as a positive control of redox imbalance, under both normoxic and hypoxic (2% oxygen for 24?h) conditions. Lifespan was used to detect the effects of hypoxic treatment and differences were analysed by means of Kaplan-Meier survival curves and log-rank tests. Electron paramagnetic resonance spectroscopy was used to measure ROS levels and analysis of variance was used to estimate the effects of hypoxic treatment and to assess ROS differences between strains. We observed that the genetic background is a relevant factor involved in D. melanogaster longevity and ROS levels. Indeed, as expected, in normoxia Sod1n1 are the shortest-lived, while the wild-type strains, despite a longer lifespan, show some differences, with the Canton-S line displaying the lowest mortality rate. After hypoxic stress these variances are amplified, with Berlin-K flies showing the highest mortality rate and most evident reduction of lifespan. Moreover, our analysis highlighted differential effects of hypoxia on redox balance/unbalance. Canton-S flies had the lowest increase of ROS level compared to all the other strains, confirming it to be the less sensitive to hypoxic stress. Sod1n1 flies displayed the highest ROS levels in normoxia and after hypoxia. These results should be used to further standardize future Drosophila research models designed to investigate genes and pathways that may be involved in lifespan and/or ROS, as well as comparative studies on specific mutant strains.
  
  © 2022. Published by The Company of Biologists Ltd.
  
  Guarda su PubMed

• Effects of Prolonged Exposure to Hypobaric Hypoxia on Oxidative Stress: Overwintering in Antarctic Concordia Station.
  Oxid Med Cell Longev

  2022 ;2022():4430032. doi: 4430032.
  
  Mrakic-Sposta Simona, Montorsi Michela, Porcelli Simone, Marzorati Mauro, Healey Beth, Dellanoce Cinzia, Vezzoli Alessandra
  
  Abstract
  
  Concordia Station is the permanent, research station on the Antarctic Plateau at 3230?m. During the eleventh winter-over campaign (DC11-2015; February 2015 to November 2015) at Antarctic Concordia Station, 13 healthy team members were studied and blood samples were collected at six different time points: baseline measurements (T0), performed at sea level before the departure, and during the campaign at 3, 7, 20, 90, and 300 days after arrival at Concordia Station. Reducing the partial pressure of O as barometric pressure falls, hypobaric hypoxia (HH) triggers several physiological adaptations. Among the others, increased oxidative stress and enhanced generation of reactive oxygen/nitrogen species (ROS/RNS), resulting in severe oxidative damage, were observed, which can share potential physiopathological mechanisms associated with many diseases. This study characterized the extent and time-course changes after acute and chronic HH exposure, elucidating possible fundamental mechanisms of adaptation. ROS, oxidative stress biomarkers, nitric oxide, and proinflammatory cytokines significantly increased (range 24-135%) during acute and chronic hypoxia exposure (peak 20 day) with a decrease in antioxidant capacity (peak 90 day: -52%). Results suggest that the adaptive response of oxidative stress balance to HH requires a relatively long time, more than 300 days, as all the observed variables do not return to the preexposition level. These findings may also be relevant to patients in whom oxygen availability is limited through disease (i.e., chronic heart and lung and/or kidney disease) and/or during long-duration space missions.
  
  Copyright © 2022 Simona Mrakic-Sposta et al.
  
  Guarda su PubMed

• OxInflammation at High Altitudes: A Proof of Concept from the Himalayas.
  Antioxidants (Basel)

  2022 Feb;11(2):. doi: 368.
  
  Mrakic-Sposta Simona, Biagini Denise, Bondi Danilo, Pietrangelo Tiziana, Vezzoli Alessandra, Lomonaco Tommaso, Di Francesco Fabio, Verratti Vittore
  
  Abstract
  
  High-altitude locations are fascinating for investigating biological and physiological responses in humans. In this work, we studied the high-altitude response in the plasma and urine of six healthy adult trekkers, who participated in a trek in Nepal that covered 300 km in 19 days along a route in the Kanchenjunga Mountain and up to a maximum altitude of 5140 m. Post-trek results showed an unbalance in redox status, with an upregulation of ROS (+19%), NOx (+28%), neopterin (+50%), and pro-inflammatory prostanoids, such as PGE (+120%) and 15-deoxy-delta12,14-PGJ (+233%). The isoprostane 15-F-IsoP was associated with low levels of TAC (-18%), amino-thiols, omega-3 PUFAs, and anti-inflammatory CYP450 EPA-derived mediators, such as DiHETEs. The deterioration of antioxidant systems paves the way to the overload of redox and inflammative markers, as triggered by the combined physical and hypoxic stressors. Our data underline the link between oxidative stress and inflammation, which is related to the concept of OxInflammation into the altitude hypoxia fashion.
  
  Guarda su PubMed

• Oxidative stress and motion sickness in one crew during competitive offshore sailing.
  Sci Rep

  2022 Jan;12(1):1142. doi: 1142.
  
  Giacon Tommaso Antonio, Bosco Gerardo, Vezzoli Alessandra, Dellanoce Cinzia, Cialoni Danilo, Paganini Matteo, Mrakic-Sposta Simona
  
  Abstract
  
  Competitive Offshore Ocean Sailing is a highly demanding activity in which subjects are exposed to psychophysical stressors for a long time. To better define the physiological adaptations, we investigated the stress response of subjects exposed to 3-days long ocean navigation with disruption of circadian rhythms. 6 male subjects were involved in the study and provided urine and saliva samples before setting sail, during a single day of inshore sailing, during 3-days long ocean navigation, and at the arrival, to measure oxidative stress, cortisol, nitric oxide metabolites (NOx) and metabolic response. Motion Sickness questionnaires were also administered during the navigation. The crew suffered a mean weight loss of 1.58 kg. After the long navigation, a significant increase in ROS production and decrease in total antioxidant capacity and uric acid levels were observed. Lipid peroxidation, NO metabolites, ketones, creatinine, and neopterin levels were also increased. Furthermore, a significant increase in cortisol levels was measured. Finally, we found a correlation between motion sickness questionnaires with the increase of NOx, and no correlation with cortisol levels. Physical and psychological stress response derived from offshore sailing resulted in increased oxidative stress, nitric oxide metabolites, and cortisol levels, unbalanced redox status, transient renal function impairment, and ketosis. A direct correlation between motion sickness symptoms evaluated through questionnaires and NOx levels was also found.
  
  © 2022. The Author(s).
  
  Guarda su PubMed

• Full-Face Mask Use during SCUBA Diving Counters Related Oxidative Stress and Endothelial Dysfunction.
  Int J Environ Res Public Health

  2022 Jan;19(2):. doi: 965.
  
  Levenez Morgan, Lambrechts Kate, Mrakic-Sposta Simona, Vezzoli Alessandra, Germonpré Peter, Pique Hadrien, Virgili Fabio, Bosco Gerardo, Lafère Pierre, Balestra Costantino
  
  Abstract
  
  Impaired flow mediated dilation (FMD), an index of vascular stress, is known after SCUBA diving. This is related to a dysfunction of nitric oxide (NO) availability and a disturbance of the redox status, possibly induced by hyperoxic/hyperbaric gas breathing. SCUBA diving is usually performed with a mask only covering "half face" (HF) and therefore forcing oral breathing. Nasal NO production is involved in vascular homeostasis and, as consequence, can significantly reduce NO possibly promoting vascular dysfunction. More recently, the utilization of "full-face" (FF) mask, allowing nasal breathing, became more frequent, but no reports are available describing their effects on vascular functions in comparison with HF masks. In this study we assessed and compared the effects of a standard shallow dive (20 min at 10 m) wearing either FF or a HF mask on different markers of vascular function (FMD), oxidative stress (ROS, 8-iso-PGF2?) and NO availability and metabolism (NO, NOx and 3-NT and iNOS expression). Data from a dive breathing a hypoxic (16% O at depth) gas mixture with HF mask are shown allowing hyperoxic/hypoxic exposure. Our data suggest that nasal breathing might significantly reduce the occurrence of vascular dysfunction possibly due to better maintenance of NO production and bioavailability, resulting in a better ability to counter reactive oxygen and nitrogen species. Besides the obvious outcomes in terms of SCUBA diving safety, our data permit a better understanding of the effects of oxygen concentrations, either in normal conditions or as a strategy to induce selected responses in health and disease.
  
  Guarda su PubMed

• JAB1 deletion in oligodendrocytes causes senescence-induced inflammation and neurodegeneration in mice.
  J Clin Invest

  2022 Feb;132(3):. doi: e145071.
  
  Rivellini Cristina, Porrello Emanuela, Dina Giorgia, Mrakic-Sposta Simona, Vezzoli Alessandra, Bacigaluppi Marco, Gullotta Giorgia Serena, Chaabane Linda, Leocani Letizia, Marenna Silvia, Colombo Emanuela, Farina Cinthia, Newcombe Jia, Nave Klaus-Armin, Pardi Ruggero, Quattrini Angelo, Previtali Stefano C
  
  Abstract
  
  Oligodendrocytes are the primary target of demyelinating disorders, and progressive neurodegenerative changes may evolve in the CNS. DNA damage and oxidative stress are considered key pathogenic events, but the underlying molecular mechanisms remain unclear. Moreover, animal models do not fully recapitulate human diseases, complicating the path to effective treatments. Here we report that mice with cell-autonomous deletion of the nuclear COP9 signalosome component CSN5 (JAB1) in oligodendrocytes develop DNA damage and defective DNA repair in myelinating glial cells. Interestingly, oligodendrocytes lacking JAB1 expression underwent a senescence-like phenotype that fostered chronic inflammation and oxidative stress. These mutants developed progressive CNS demyelination, microglia inflammation, and neurodegeneration, with severe motor deficits and premature death. Notably, blocking microglia inflammation did not prevent neurodegeneration, whereas the deletion of p21CIP1 but not p16INK4a pathway ameliorated the disease. We suggest that senescence is key to sustaining neurodegeneration in demyelinating disorders and may be considered a potential therapeutic target.
  
  Guarda su PubMed

• Oxidative Stress and Inflammation, MicroRNA, and Hemoglobin Variations after Administration of Oxygen at Different Pressures and Concentrations: A Randomized Trial.
  Int J Environ Res Public Health

  2021 Sep;18(18):. doi: 9755.
  
  Bosco Gerardo, Paganini Matteo, Giacon Tommaso Antonio, Oppio Alberto, Vezzoli Alessandra, Dellanoce Cinzia, Moro Tatiana, Paoli Antonio, Zanotti Federica, Zavan Barbara, Balestra Costantino, Mrakic-Sposta Simona
  
  Abstract
  
  Exercise generates reactive oxygen species (ROS), creating a redox imbalance towards oxidation when inadequately intense. Normobaric and hyperbaric oxygen (HBO) breathed while not exercising induces antioxidant enzymes expression, but literature is still poor. Twenty-two athletes were assigned to five groups: controls; 30%, or 50% O; 100% O (HBO) at 1.5 or 2.5 atmosphere absolute (ATA). Twenty treatments were administered on non-training days. Biological samples were collected at T0 (baseline), T1 (end of treatments), and T2 (1 month after) to assess ROS, antioxidant capacity (TAC), lipid peroxidation, redox (amino-thiols) and inflammatory (IL-6, 10, TNF-?) status, renal function (i.e., neopterin), miRNA, and hemoglobin. At T1, O mixtures and HBO induced an increase of ROS, lipid peroxidation and decreased TAC, counterbalanced at T2. Furthermore, 50% O and HBO treatments determined a reduced state in T2. Neopterin concentration increased at T1 breathing 50% O and HBO at 2.5 ATA. The results suggest that 50% O treatment determined a reduced state in T2; HBO at 1.5 and 2.5 ATA similarly induced protective mechanisms against ROS, despite the latter could expose the body to higher ROS levels and neopterin concentrations. HBO resulted in increased Hb levels and contributed to immunomodulation by regulating interleukin and miRNA expression.
  
  Guarda su PubMed

• Hypoxic and Hyperoxic Breathing as a Complement to Low-Intensity Physical Exercise Programs: A Proof-of-Principle Study.
  Int J Mol Sci

  2021 Sep;22(17):. doi: 9600.
  
  Balestra Costantino, Lambrechts Kate, Mrakic-Sposta Simona, Vezzoli Alessandra, Levenez Morgan, Germonpré Peter, Virgili Fabio, Bosco Gerardo, Lafère Pierre
  
  Abstract
  
  Inflammation is an adaptive response to both external and internal stimuli including infection, trauma, surgery, ischemia-reperfusion, or malignancy. A number of studies indicate that physical activity is an effective means of reducing acute systemic and low-level inflammation occurring in different pathological conditions and in the recovery phase after disease. As a proof-of-principle, we hypothesized that low-intensity workout performed under modified oxygen supply would elicit a "metabolic exercise" inducing a hormetic response, increasing the metabolic load and oxidative stress with the same overall effect expected after a higher intensity or charge exercise. Herein, we report the effect of a 5-week low-intensity, non-training, exercise program in a group of young healthy subjects in combination with the exposure to hyperoxia (30% and 100% pO, respectively) or light hypoxia (15% pO) during workout sessions on several inflammation and oxidative stress parameters, namely hemoglobin (Hb), redox state, nitric oxide metabolite (NOx), inducible nitric oxide synthase (iNOS), inflammatory cytokine expression (TNF-?, interleukin (IL)-6, IL-10), and renal functional biomarkers (creatinine, neopterin, and urates). We confirmed our previous reports demonstrating that intermittent hyperoxia induces the normobaric oxygen paradox (NOP), a response overlapping the exposure to hypoxia. Our data also suggest that the administration of modified air composition is an expedient complement to a light physical exercise program to achieve a significant modulation of inflammatory and immune parameters, including cytokines expression, iNOS activity, and oxidative stress parameters. This strategy can be of pivotal interest in all those conditions characterized by the inability to achieve a sufficient workload intensity, such as severe cardiovascular alterations and articular injuries failing to effectively gain a significant improvement of physical capacity.
  
  Guarda su PubMed

• Comment on Menzel et al. Common and Novel Markers for Measuring Inflammation and Oxidative Stress Ex Vivo in Research and Clinical Practice-Which to Use Regarding Disease Outcomes? 2021, , 414.
  Antioxidants (Basel)

  2021 May;10(6):. doi: 836.
  
  Mrakic-Sposta Simona, Gussoni Maristella, Montorsi Michela, Vezzoli Alessandra
  
  Abstract
  
  Recently, Menzel A et al. published a review titled "Origin and Physiological Aspects of Oxidative Stress (OS), inflammation and markers of OS, relation to disease and practical aspects" [...].
  
  Guarda su PubMed

• Antioxidant Activity with Increased Endogenous Levels of Vitamin C, E and A Following Dietary Supplementation with a Combination of Glutathione and Resveratrol Precursors.
  Nutrients

  2020 Oct;12(11):. doi: 3224.
  
  Biswas Priscilla, Dellanoce Cinzia, Vezzoli Alessandra, Mrakic-Sposta Simona, Malnati Mauro, Beretta Alberto, Accinni Roberto
  
  Abstract
  
  The effects of two different dietary supplements on the redox status of healthy human participants were evaluated. The first supplement (GluS, Glutathione Synthesis) contains the precursors for the endogenous synthesis of glutathione and the second (GluReS, Glutathione and Resveratrol Synthesis) contains in addition polydatin, a precursor of resveratrol. To assess the influence of GluS and GluReS on the redox status, ten thiol species and three vitamins were measured before (t0) and after 8 weeks (t1) of dietary supplementation. An inflammatory marker, neopterin, was also assessed at the same time points. Both supplements were highly effective in improving the redox status by significantly increasing the reduced-glutathione (GSH) content and other reduced thiol species while significantly decreasing the oxidized species. The positive outcome of the redox status was most significant in the GluRes treatment group which also experienced a significant reduction in neopterin levels. Of note, the endogenous levels of vitamins C, E and A were significantly increased in both treatment groups, with best results in the GluReS group. While both dietary supplements significantly contributed to recognized antioxidant and anti-inflammatory outcomes, the effects of GluReS, the combination of glutathione and resveratrol precursors, were more pronounced. Thus, dietary supplementation with GluReS may represent a valuable strategy for maintaining a competent immune status and a healthy lifespan.
  
  Guarda su PubMed

• Change in Oxidative Stress Biomarkers During 30 Days in Saturation Dive: A Pilot Study.
  Int J Environ Res Public Health

  2020 Sep;17(19):. doi: 7118.
  
  Mrakic-Sposta Simona, Vezzoli Alessandra, D'Alessandro Federica, Paganini Matteo, Dellanoce Cinzia, Cialoni Danilo, Bosco Gerardo
  
  Abstract
  
  Saturation diving allows divers to reduce the risk of decompression sickness while working at depth for prolonged periods but may increase reactive oxygen species (ROS) production. Such modifications can affect endothelial function by exacerbating oxidative stress. This study investigated the effects of saturation diving on oxidative stress damage. Redox status was evaluated through: ROS production; total antioxidant capacity (TAC); nitric oxide metabolites (NOx); nitrotyrosine (3-NT); and lipid peroxidation (8-iso-PGF2?) assessment. Creatinine and neopterin were analyzed as markers of renal function and damage. Measurements were performed on saliva and urine samples obtained at four time points: pre; deep; post; and 24 h post. Four divers were included in the study. After the saturation dive (post), significant (
  Guarda su PubMed

• Influence of Dietary Supplementation for Hyperhomocysteinemia Treatments.
  Nutrients

  2020 Jun;12(7):. doi: 1957.
  
  Vezzoli Alessandra, Dellanoce Cinzia, Caimi Teresa Maria, Vietti Daniele, Montorsi Michela, Mrakic-Sposta Simona, Accinni Roberto
  
  Abstract
  
  Hyperhomocysteinemia is recognized as risk factor for cardiovascular and age-associated diseases. Folic acid supplementation efficiently lowers plasma homocysteine (Hcy) levels, but high intake may negatively affect health because of unnatural levels of unmetabolized folic acid in the systemic circulation. Oxoproline (Oxo) provides by glutamic acid production an increase of intracellular folic acid trapping. Aim of this study was to compare the efficacy of three supplementation protocols: (1) traditional therapy (5-methyl-tetrahydrofolate: 15 mg/day); (2) 5 mL/day of Oxo with 300 ?g folic acid (oxifolic); (3) 5 mL/day of Oxo alone (magnesio+) in a 90 days randomized trial on thirty-two moderate hyperhomocysteinemic (18.6 ± 2.4 ?mol.L) patients (age 48 ± 14 yrs). Thiols: cysteine (Cys), cysteinylglycine (Cys-Gly) and glutathione levels were assessed too. Every supplementation induced significant ( range
  Guarda su PubMed

• Commentary on: "Targeted and untargeted metabolomics applied to occupational exposure to hyperbaric atmosphere".
  Toxicol Lett

  2020 May;330():71-72. doi: 10.1016/j.toxlet.2020.05.021.
  
  Mrakic-Sposta Simona, Bosco Gerardo, Vezzoli Alessandra
  
  
  
  Guarda su PubMed

• Acute Effects of Triathlon Race on Oxidative Stress Biomarkers.
  Oxid Med Cell Longev

  2020 ;2020():3062807. doi: 3062807.
  
  Mrakic-Sposta Simona, Gussoni Maristella, Vezzoli Alessandra, Dellanoce Cinzia, Comassi Mario, Giardini Guido, Bruno Rosa Maria, Montorsi Michela, Corciu Anca, Greco Fulvia, Pratali Lorenza
  
  Abstract
  
  The response to strenuous exercise was investigated by reactive oxygen species (ROS) production, oxidative damage, thiol redox status, and inflammation assessments in 32 enrolled triathlon athletes (41.9 ± 7.9 yrs) during Ironman® (IR), or half Ironman® (HIR) competition. In biological samples, inflammatory cytokines, aminothiols (glutathione (GSH), homocysteine (Hcy), cysteine (Cys), and cysteinylglycine (CysGly)), creatinine and neopterin, oxidative stress (OxS) biomarkers (protein carbonyl (PC), thiobarbituric acid-reactive substances (TBARS)), and ROS were assessed. Thirteen HIR and fourteen IR athletes finished the race. Postrace, ROS (HIR +20%; IR +28%;
  Copyright © 2020 Simona Mrakic-Sposta et al.
  
  Guarda su PubMed

• Moderate Intensity Resistive Training Reduces Oxidative Stress and Improves Muscle Mass and Function in Older Individuals.
  Antioxidants (Basel)

  2019 Sep;8(10):. doi: 431.
  
  Vezzoli Alessandra, Mrakic-Sposta Simona, Montorsi Michela, Porcelli Simone, Vago Paola, Cereda Ferdinando, Longo Stefano, Maggio Marcello, Narici Marco
  
  Abstract
  
  An innovative moderate-intensity resistive exercise-training (RT) program was tested in thirty-five sarcopenic elders (SAR). The subjects were randomized into two groups: SAR training (SAR-RT), n = 20, 73.0 ± 5.5 years, or SAR non-training (SAR-NT), n = 15, 71.7 ± 3.4 years. The training consisted of 12-week progressive RT, thrice/week, at 60% one-repetition maximum (1RM), 3 sets, 14-16 repetitions for both upper and lower limbs. The pre and post intervention measurements included: the skeletal muscle index (SMI%); strength (1RM); stair-climbing power (SCP); muscle thickness (MT) of vastus lateralis (VL) and elbow flexors (EF), VL pennation angle (PA), rectus femoris (RF) anatomical cross-sectional area (ACSA); reactive oxygen species (ROS), total antioxidant capacity (TAC), protein carbonyls (PC), thiobarbituric acid-reactive substances (TBARS), 8-isoprostane (8-iso-PGF2-?), 8-OH-2-deoxyguanosine (8-OH-dG), as markers of oxidative stress/damage (OxS). In SAR-RT, SCP increased by 7.7% ( 0.01), MT increased by 5.5% for VL, 10.4% for EF and PA increased by 13.4% for VL ( 0.001 for all). The RF ACSA increased by 14.5% ( 0.001). 1RM significantly increased by at least 67% for all muscles tested. Notably muscle strength (1RM) positively correlated ( 0.001) with TAC and negatively with PC ( 0.001). In conclusion, moderate intensity RT is an effective strategy to increase muscle mass and strength in SAR, while minimizing OxS.
  
  Guarda su PubMed

• Oxidative stress assessment in breath-hold diving.
  Eur J Appl Physiol

  2019 Dec;119(11-12):2449-2456. doi: 10.1007/s00421-019-04224-4.
  
  Mrakic-Sposta Simona, Vezzoli Alessandra, Rizzato Alex, Della Noce Cinzia, Malacrida Sandro, Montorsi Michela, Paganini Matteo, Cancellara Pasqua, Bosco Gerardo
  
  Abstract
  
  PURPOSE:
  Breath-hold diving results in significant changes in blood gases' levels. Challenging variations in oxygen partial pressures may induce reactive oxygen species (ROS) production that exacerbate oxidative stress and, consequently, affect endothelial function. The aim of this study was to investigate the effects of breath-hold diving on oxidative stress damage, assessing ROS production. Nitric oxide metabolites, inducible nitric oxide synthase (iNOS), aminothiols, and renal function were evaluated too as markers of redox status and renal damage.
  
  METHODS:
  ROS production was assessed with electron paramagnetic resonance. Oxidative status values were measured at pre- and post-40 m dive in a deep swimming pool (Y-40) from six divers (mean age 46.6?±?9.3 years; height 176?±?4 cm; BMI 25?±?2.9 kg/m).
  
  RESULTS:
  Significant (p?0.05) increases at post-dive of ROS production rate (0.158?±?0.003 vs 0.195?±?0.006 ?mol min), lipid peroxidation (8-isoprostane: 375.67?±?195.62 vs 420.49?±?232.31 pg mg creatinine), nitrate (27.91?±?19.71 vs 30.80?±?20.44 ?M), iNOS (31.30?±?4.52 vs 35.68?±?6.72 IU mL) and neopterin concentration (96.20?±?40.41 vs 118.76?±?27.84 ?mol mol creatinine) were recorded. Conversely, the antioxidant capacity significantly decreased (3.423?±?0.089 vs 3.015?±?0.284 mM) after immersion.
  
  CONCLUSION:
  Overproduction of ROS and consequent oxidative damage to lipids of membrane and antioxidant capacity decreasing reflect also a hypoxic condition, which in the breath-hold diving typically occurs in the last few meters below the surface. iNOS produces NO in large quantities under the examined extreme conditions. Neopterin and creatinine concentration level increased, suggesting an "impairment of renal function" as a likely physiological response to PaO variations during dive activity.
  
  Guarda su PubMed

• Transcription Factors Regulation in Human Peripheral White Blood Cells during Hypobaric Hypoxia Exposure: an in-vivo experimental study.
  Sci Rep

  2019 Jul;9(1):9901. doi: 9901.
  
  Malacrida Sandro, Giannella Alessandra, Ceolotto Giulio, Reggiani Carlo, Vezzoli Alessandra, Mrakic-Sposta Simona, Moretti Sarah, Turner Rachel, Falla Marika, Brugger Hermann, Strapazzon Giacomo
  
  Abstract
  
  High altitude is a natural laboratory, within which the clinical study of human physiological response to hypobaric hypoxia (HH) is possible. Failure in the response results in progressive hypoxemia, inflammation and increased tissue oxidative stress (OxS). Thus, investigating temporal changes in key transcription factors (TFs) HIF-1?, HIF-2?, NF-?B and NRF2 mRNA levels, relative to OxS and inflammatory markers, may reveal molecular targets which contrast deleterious effects of hypoxia. Biological samples and clinical data from 15 healthy participants were collected at baseline and after rapid, passive ascent to 3830?m (24?h and 72?h). Gene expression was assessed by qPCR and ROS generation was determined by EPR spectroscopy. Oxidative damage and cytokine levels were estimated by immuno or enzymatic methods. Hypoxia transiently enhanced HIF-1? mRNA levels over time reaching a peak after 24?h. Whereas, HIF-2? and NRF2 mRNA levels increased over time. In contrast, the NF-?B mRNA levels remained unchanged. Plasma levels of IL-1? and IL-6 also remained within normal ranges. ROS production rate and markers of OxS damage were significantly increased over time. The analysis of TF-gene expression suggests that HIF-1? is a lead TF during sub-acute HH exposure. The prolongation of the HH exposure led to a switch between HIF-1? and HIF-2?/NRF2, suggesting the activation of new pathways. These results provide new insights regarding the temporal regulation of TFs, inflammatory state, and ROS homeostasis involved in human hypoxic response, potentially also relevant to the mediation of diseases that induce a hypoxic state.
  
  Guarda su PubMed

• Effects of Combined Physical and Cognitive Virtual Reality-Based Training on Cognitive Impairment and Oxidative Stress in MCI Patients: A Pilot Study.
  Front Aging Neurosci

  2018 ;10():282. doi: 282.
  
  Mrakic-Sposta Simona, Di Santo Simona G, Franchini Flaminia, Arlati Sara, Zangiacomi Andrea, Greci Luca, Moretti Sarah, Jesuthasan Nithiya, Marzorati Mauro, Rizzo Giovanna, Sacco Marco, Vezzoli Alessandra
  
  Abstract
  
  The growing elderly population and the increased incidence of mild cognitive impairment (MCI) and Alzheimer's disease (AD) call for the improvement of the quality and the efficacy of the healthcare and social support services. Exercise and cognitive stimulation have been demonstrated to mitigate cognitive impairment and oxidative stress (OxS) has been recognized as a factor that contributes to the advancement of neurodegenerative diseases. Taking these aspects into account, the impact of a novel virtual reality (VR)-based program combining aerobic exercise and cognitive training has been evaluated in the pilot study proposed here. Ten patients (aged 73.3 ± 5.7 years) with MCI (Mini-Mental State Examination, MMSE: 23.0 ± 3.4) were randomly assigned to either 6 weeks physical and cognitive training (EXP) or control (CTR) group. Evaluations of cognitive profile, by a neuropsychological tests battery, and OxS, by collection of blood and urine samples, were performed before and at the end of the experimental period. The assessment of the patients' opinions toward the intervention was investigated through questionnaires. EXP group showed a tendency towards improvements in the MMSE, in visual-constructive test and visuo-spatial tests of attention, while CTR worsened. EXP group showed a greater improvement than CTR in the executive test, memory functions and verbal fluency. No statistical significance was obtained when comparing within and between both the groups, probably due to small number of subjects examined, which amplifies the effect of the slight heterogeneity in scores recorded. Despite a greater worsening of Daily Living Activities tests, all participants reported a better performance in real life, thanks to the elicited self-perceived improvement. After training intervention OxS (i.e., reactive oxygen species (ROS) production, oxidative damage of lipids and DNA) decreased resulting in significantly (range
  Guarda su PubMed

• Hyperbaric oxygen therapy ameliorates osteonecrosis in patients by modulating inflammation and oxidative stress.
  J Enzyme Inhib Med Chem

  2018 Dec;33(1):1501-1505. doi: 10.1080/14756366.2018.1485149.
  
  Bosco Gerardo, Vezzani Giuliano, Mrakic Sposta Simona, Rizzato Alex, Enten Garrett, Abou-Samra Abdullah, Malacrida Sandro, Quartesan Silvia, Vezzoli Alessandra, Camporesi Enrico
  
  Abstract
  
  Early stages of avascular necrosis of the femoral head (AVNFH) can be conservatively treated with hyperbaric oxygen therapy (HBOT). This study investigated how HBOT modulates inflammatory markers and reactive oxygen species (ROS) in patients with AVNFH. Twenty-three male patients were treated with two cycles of HBOT, 30 sessions each with a 30 days break between cycles. Each session consisted of 90?minutes of 100% inspired oxygen at 2.5 absolute atmospheres of pressure. Plasma levels of tumor necrosis factor alfa (TNF-?), interleukin 6 (IL-6), interleukin 1 beta (IL-1?) and ROS production were measured before treatment (T0), after 15 and 30 HBOT sessions (T1 and T2), after the 30-day break (T3), and after 60 sessions (T4). Results showed a significant reduction in TNF-? and IL-6 plasma levels over time. This decrease in inflammatory markers mirrored observed reductions in bone marrow edema and reductions in patient self-reported pain.
  
  Guarda su PubMed

• Acute Cardiovascular Adaptation to Strenuous Exercise: An Integrative Ultrasound Study.
  J Ultrasound Med

  2019 Feb;38(2):463-470. doi: 10.1002/jum.14719.
  
  Bianchini Elisabetta, Bruno Rosa Maria, Di Lascio Nicole, Vezzoli Alessandra, Mrakic-Sposta Simona, Corciu Anca Irina, Comassi Mario, Pratali Lorenza
  
  Abstract
  
  OBJECTIVES:
  The aim of this study was to evaluate the acute effects of participation in an Ironman distance triathlon competition on arterial function by ultrasound, in relation to cardiac function and body water content.
  
  METHODS:
  Twenty-eight male triathletes participating in an Ironman distance competition underwent carotid, femoral, and cardiac ultrasound examinations. Moreover, the presence of extravascular lung water was identified by lung echo B-lines (echogenic coherent wedge-shaped signal with a narrow origin from the hyperechoic pleural line) at rest and within 20 minutes of arrival.
  
  RESULTS:
  At the end of the competition, athletes showed an increased heart rate (mean?±?SD, from 60.2?±?13.1 to 82.8?±?15.6 beats/min; P?.0001) and unchanged mean blood pressure (from 93?±?14 to 91?±?10?mm Hg; P?>?.05) in the presence of negligible dehydration (total body water from 48.0?±?4.0 to 46.5?±?3.9?kg; P?>?.05). Cardiac output increased (from 5.5?±?1.2 to 6.7?±?2.4?L/min; P?.05) in the presence of an unchanged stroke volume (from 64?±?14 to 59?±?16?mL; P?>?.05) and unchanged left ventricular elastance (from 1.52?±?0.48 to 1.39?±?0.48?mm Hg/mL/m ; P?>?.05). The mean carotid diameter increased (from 7.19?±?0.65 to 7.61?±?0.76?mm; P?.05), whereas the mean femoral diameter was unchanged at the end of the competition (from 10.41?±?0.83 to 10.49?±?0.82?mm; P?>?.05). Carotid intima-media thickness was significantly reduced (from 537?±?70 to 495?±?70??m; P?.05), whereas B-lines increased significantly after the competition (from 1 [0-4] to 12 [5-23]; P?.0001).
  
  CONCLUSIONS:
  These data suggest different acute functional adaptation in central arteries with respect to peripheral leg vessels.
  
  © 2018 by the American Institute of Ultrasound in Medicine.
  
  Guarda su PubMed

• Oxidative stress as a biomarker for monitoring treated celiac disease.
  Clin Transl Gastroenterol

  2018 Jun;9(6):157. doi: 157.
  
  Moretti Sarah, Mrakic-Sposta Simona, Roncoroni Leda, Vezzoli Alessandra, Dellanoce Cinzia, Monguzzi Erika, Branchi Federica, Ferretti Francesca, Lombardo Vincenza, Doneda Luisa, Scricciolo Alice, Elli Luca
  
  Abstract
  
  INTRODUCTION:
  High levels of reactive oxygen species (ROS) and impaired antioxidant defense systems lead to oxidative stress (OxS) and tissue injury in different intestinal and extra intestinal conditions, including celiac disease (CD). The aim of the present study was to investigate the role and potential use of ROS and other biomarkers of OxS in the clinical management of CD.
  
  METHODS:
  We collected duodenal specimens and blood samples from naïve patients (N-CD), patients on a gluten free diet (GFD) including responders (CD-GFD) and non-responders (NRCD). We measured plasmatic ROS production (electron paramagnetic resonance, EPR), lipid peroxidation (thiobarbituric acid-reactive substances, TBARS), protein oxidation (protein carbonyl, PC), total antioxidant capacity (TAC), nitric oxides and glutathione (GSH) in erythrocytes.
  
  RESULTS:
  Fifty-four patients affected by CD were enrolled (17 N-CD, 18 CD-GFD and 19 NRCD; 44?F; age 44?±?13 years). A significant increase of plasmatic OxS biomarkers (ROS, peroxidated lipids, oxidized proteins, and nitrate concentrations) and decrease of antioxidant species (TAC and GSH levels) were found in NRCD and N-CD compared to CD-GFD. Comparably, a significant direct relationship between the severity of duodenal atrophy, ROS production rates and TBARS was found; conversely, TAC and GSH presented an inverse correlation.
  
  DISCUSSION:
  OxS is involved in CD tissue damage and correlates with the degree of duodenal atrophy. These findings suggest the possible role of OxS biomarkers as indicators of CD activity during the clinical follow-up.
  
  Guarda su PubMed

• R(+)-Thioctic Acid Effects on Oxidative Stress and Peripheral Neuropathy in Type II Diabetic Patients: Preliminary Results by Electron Paramagnetic Resonance and Electroneurography.
  Oxid Med Cell Longev

  2018 ;2018():1767265. doi: 1767265.
  
  Mrakic-Sposta Simona, Vezzoli Alessandra, Maderna Luca, Gregorini Francesca, Montorsi Michela, Moretti Sarah, Greco Fulvia, Cova Emanuela, Gussoni Maristella
  
  Abstract
  
  OBJECTIVES:
  Diabetic neuropathy is the most common complication of diabetes. The idea of alterations in energy metabolism in diabetes is emerging. The biogenic antioxidant R(+)-thioctic acid has been successfully used in the treatment of diabetic polyneuropathic (DPN) patients.
  
  METHODS:
  The effects of R(+)-thioctic acid (1 tablet, 1.6?g) administration were evaluated in 12 DPN patients at baseline and at 15, 30, 60, and 120 administration days throughout the assessment of oxidative stress (OxS); ROS production rate by electron paramagnetic resonance (EPR) technique; and oxidative damage biomarkers (thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PC)), electroneurography (ENG) and visual analogue scale.
  
  RESULTS:
  Supplementation induced significant changes (
  CONCLUSION:
  The results strongly indicate that an increased antioxidant capacity plays an important role in OxS, nerve conduction velocity, pain, and general wellness improvement. Nevertheless, the effects of the antioxidant compound were found positive up to 60 days. Then, a hormesis effect was observed. Novelty of the research would be a challenge for investigators to carefully address issues, including dose range factors, appropriate administration time, and targeting population to counteract possible "boomerang effects." The great number of monitored parameters would firmly stress these conclusions.
  
  Guarda su PubMed

• Author Correction: Lack of acclimatization to chronic hypoxia in humans in the Antarctica.
  Sci Rep

  2018 May;8(1):7063. doi: 7063.
  
  Porcelli Simone, Marzorati Mauro, Healey Beth, Terraneo Laura, Vezzoli Alessandra, Bella Silvia Della, Dicasillati Roberto, Samaja Michele
  
  Abstract
  
  A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
  
  Guarda su PubMed

• Ergogenic effects of beetroot juice supplementation during severe-intensity exercise in obese adolescents.
  Am J Physiol Regul Integr Comp Physiol

  2018 Sep;315(3):R453-R460. doi: 10.1152/ajpregu.00017.2018.
  
  Rasica Letizia, Porcelli Simone, Marzorati Mauro, Salvadego Desy, Vezzoli Alessandra, Agosti Fiorenza, De Col Alessandra, Tringali Gabriella, Jones Andrew M, Sartorio Alessandro, Grassi Bruno
  
  Abstract
  
  Previous studies showed a higher O cost of exercise, and therefore, a reduced exercise tolerance in patients with obesity during constant work rate (CWR) exercise compared with healthy subjects. Among the ergogenic effects of dietary nitrate ([Formula: see text]) supplementation in sedentary healthy subjects, a reduced O cost and enhanced exercise tolerance have often been demonstrated. The aim of this study was to evaluate the effects of beetroot juice (BR) supplementation, rich in [Formula: see text], on physiological variables associated with exercise tolerance in adolescents with obesity. In a double-blind, randomized crossover study, 10 adolescents with obesity (8 girls, 2 boys; age?=?16?±?1 yr; body mass index?=?35.2?±?5.0 kg/m) were tested after 6 days of supplementation with BR (5 mmol [Formula: see text] per day) or placebo (PLA). Following each supplementation period, patients carried out two repetitions of 6-min moderate-intensity CWR exercise and one severe-intensity CWR exercise until exhaustion. Plasma [Formula: see text] concentration was significantly higher in BR versus PLA (108?±?37 vs. 15?±?5 ?M, P
  Guarda su PubMed

• Different Training Modalities Improve Energy Cost and Performance in Master Runners.
  Front Physiol

  2018 ;9():21. doi: 21.
  
  Pugliese Lorenzo, Porcelli Simone, Vezzoli Alessandra, La Torre Antonio, Serpiello Fabio R, Pavei Gaspare, Marzorati Mauro
  
  Abstract
  
  The aim of this study was to compare the effects of continuous moderate-intensity and discontinuous high-intensity training on running performance in master runners. Thirty-four male master runners (47.2 ± 7.4 years) were assigned to three different groups: continuous moderate-intensity training (CMIT), discontinuous high-intensity training (DHIT), and control group (CON). CMIT and DHIT performed 8-week of supervised training (3 session·wk; ~35 km·wk) while CON maintained their normal training habits (3-4 session·wk; ~50 km·wk). Peak oxygen consumption ([Formula: see text]O) and peak running speed (v) during incremental treadmill exercise, gas exchange threshold (GET), speed at GET, energy cost of running (Cr), and 5-km performance were evaluated before and after training. Following the training period, both CMIT and DHIT significantly reduced Cr (-4.4 and -4.9%, respectively,
  Guarda su PubMed

• Lack of acclimatization to chronic hypoxia in humans in the Antarctica.
  Sci Rep

  2017 Dec;7(1):18090. doi: 18090.
  
  Porcelli Simone, Marzorati Mauro, Healey Beth, Terraneo Laura, Vezzoli Alessandra, Bella Silvia Della, Dicasillati Roberto, Samaja Michele
  
  Abstract
  
  The study was carried out at Concordia Station (Antarctic Plateau). The aim was to investigate the respiratory and haematological responses to hypoxia in healthy subjects living at constant altitude. Thirteen men and women (34.1?±?3.1 years) were exposed for 10 months to hypobaric hypoxia (oxygen level equivalent to 3800?m asl). These unique conditions enable a greater accuracy of monitoring human responses to chronic hypoxia than can be achieved elsewhere. Blood haemoglobin and erythropoietin concentrations were determined at sea level (Pre), and after 3, 7, 20, 90 and 300 days at altitude. Blood gas analysis, base excess and arterial oxygen saturation were measured at Pre, and after 150 and 300 days at altitude. Erythropoietin returned quickly to baseline level after a transient increase in the first days. Blood haemoglobin concentration started increasing at day 7 and remained markedly higher for the entire duration of the mission. At day 150 the blood carbon dioxide partial pressure was markedly reduced, and consequently blood pH remained higher at negative base excess until day 300. The arterial oxygen saturation remained lower than Pre throughout. In conclusion, humans display little capacity of hypoxia acclimatization even after ten months of constant exposure to low oxygen partial pressure.
  
  Guarda su PubMed

• Enhanced Right-Chamber Remodeling in Endurance Ultra-Trail Athletes Compared to Marathon Runners Detected by Standard and Speckle-Tracking Echocardiography.
  Front Physiol

  2017 ;8():527. doi: 527.
  
  Ujka Kristian, Bastiani Luca, D'Angelo Gennaro, Catuzzo Bruna, Tonacci Alessandro, Mrakic-Sposta Simona, Vezzoli Alessandra, Giardini Guido, Pratali Lorenza
  
  Abstract
  
  Strenuous and endurance exercise training have been associated with morphological and functional heart remodeling. Two-dimensional speckle-tracking echocardiography (STE) is a novel technique that allows an accurate quantification of global myocardium deformation. Our aim was to evaluate together left and right cardiac remodeling in different long-distance running athletes: marathon runners (42 km) (M) and endurance mountain runners (>300 Km) (UT). A total of 92 athletes (70 males, 76%) including 47 M [age 45 ± 7 years; training: 18 (9-53) yearsdays/week], 45 UT [age 42 ± 9, training: 30 (15-66) yearsdays/week] underwent conventional echocardiography and STE (Beyond Diogenes 2.0, AMID) during the agonistic season. Right ventricle (RV) end-diastolic area ( = 0.026), fractional area changing (FAC) ( = 0.008) and RV global longitudinal strain (GLS) were significantly increasedin UT athletes. Furthermore, UT showed larger right atrium (RA) volume ( = 0.03), reduced RA GLS and significantly increased RA global circumferential strain (GCS) compared to M. After adjustment for age, sex, and HR as covariates, UT showed a reduced RA GLS (OR 0.907; CI 0.856-0.961) and increased RV FAC (OR 1.172; CI: 1.044-1.317) compared to M. Athletes enrolled in UT endurance activities showed RV and RA morphological and functional remodeling to increased preload in comparison with M runners characterized by increased RV FAC and reduced RA GLS. Follow-up studies are needed to better assess the long-term clinical impact of these modifications. 2D STE is a useful tool for investigating the deformation dynamic in different sports specialties.
  
  Guarda su PubMed

• "Direct" and "Indirect" Methods to Detect Oxidative Stress During Acute or Chronic High-Altitude Exposure.
  High Alt Med Biol

  2017 Sep;18(3):303-304. doi: 10.1089/ham.2017.0067.
  
  Mrakic-Sposta Simona, Vezzoli Alessandra, Malacrida Sandro, Falla Marika, Strapazzon Giacomo
  
  
  
  Guarda su PubMed

• Oxidative stress response to acute hypobaric hypoxia and its association with indirect measurement of increased intracranial pressure: a field study.
  Sci Rep

  2016 Aug;6():32426. doi: 32426.
  
  Strapazzon Giacomo, Malacrida Sandro, Vezzoli Alessandra, Dal Cappello Tomas, Falla Marika, Lochner Piergiorgio, Moretti Sarah, Procter Emily, Brugger Hermann, Mrakic-Sposta Simona
  
  Abstract
  
  High altitude is the most intriguing natural laboratory to study human physiological response to hypoxic conditions. In this study, we investigated changes in reactive oxygen species (ROS) and oxidative stress biomarkers during exposure to hypobaric hypoxia in 16 lowlanders. Moreover, we looked at the potential relationship between ROS related cellular damage and optic nerve sheath diameter (ONSD) as an indirect measurement of intracranial pressure. Baseline measurement of clinical signs and symptoms, biological samples and ultrasonography were assessed at 262?m and after passive ascent to 3830?m (9, 24 and 72?h). After 24?h the imbalance between ROS production (+141%) and scavenging (-41%) reflected an increase in oxidative stress related damage of 50-85%. ONSD concurrently increased, but regression analysis did not infer a causal relationship between oxidative stress biomarkers and changes in ONSD. These results provide new insight regarding ROS homeostasis and potential pathophysiological mechanisms of acute exposure to hypobaric hypoxia, plus other disease states associated with oxidative-stress damage as a result of tissue hypoxia.
  
  Guarda su PubMed

• Oxidative Stress Assessment in Response to Ultraendurance Exercise: Thiols Redox Status and ROS Production according to Duration of a Competitive Race.
  Oxid Med Cell Longev

  2016 ;2016():6439037. doi: 6439037.
  
  Vezzoli Alessandra, Dellanoce Cinzia, Mrakic-Sposta Simona, Montorsi Michela, Moretti Sarah, Tonini Annamaria, Pratali Lorenza, Accinni Roberto
  
  Abstract
  
  Purpose. Response to an ultraendurance competitive race on thiols redox status, reactive oxygen species (ROS) production, and oxidative stress (OxS) was investigated according to duration. Methods. Twenty-four elite runners were examined: six completed 50?km and eighteen 100?km. Blood and urine samples were collected before and immediately after the race. Erythrocytes and plasma aminothiols by high-performance liquid chromatography, total antioxidant capacity (TAC), and OxS biomarkers (protein carbonyl (PC), thiobarbituric acid-reactive substances (TBARS), 8-isoprostane (8-iso-PGF2?), and 8-OH-2-deoxyguanosine (8-OH-dG)) by immunoenzymatic assays and ROS production by Electron Paramagnetic Resonance were assessed. Results. Significant increases (P between
  Guarda su PubMed

• A Novel Application for Cognitive Evaluation in Mountain Ultramarathons: Olfactory Assessment.
  Wilderness Environ Med

  2016 Mar;27(1):131-5. doi: 10.1016/j.wem.2015.11.013.
  
  Tonacci Alessandro, Billeci Lucia, Tartarisco Gennaro, Mastorci Francesca, Borghini Andrea, Mrakic-Sposta Simona, Moretti Sarah, Vezzoli Alessandra, Faraguna Ugo, Pioggia Giovanni, Guido Giardini, Pratali Lorenza
  
  Abstract
  
  OBJECTIVE:
  Olfactory function, a cognitive impairment biomarker, was evaluated in mountain ultramarathon (MUM) runners during the Tor des Géants race (332.5 km with an overall altitude gain of 24,000 m; altitude range 330-3296 m above the sea).
  
  METHODS:
  An Odor Identification Test was administered before (T0; n = 53), at 148.7 kms (T1; n = 32) and after the race (T2; n = 28). The effect of dehydration and sleep deprivation on olfactory function was assessed. Olfactory function was also assessed in non-MUM athletes and sedentary controls (C) at rest.
  
  RESULTS:
  A majority of the athletes completed the olfactory test at all time intervals. Olfactory function decreased throughout the race (T0: 13.8 ± 1.9, T1: 13.7 ± 1.6, T2: 13.1 ± 1.8; T0 vs T2 P = .01). There was no relationship with race time or sleep deprivation on the sense of smell throughout the competition. However, there was a combined effect with decreased olfaction during the second half of the race, while a poor relationship was seen between olfaction and total body water at midterm (T1: rs = -0.427; P = .019), but not at baseline or after the race. MUM athletes had similar olfactory scores to C (13.8 ± 1.9 vs 13.7 ± 1.4) and non-MUM (13.8 ± 1.9 vs 13.9 ± 1.6) athletes.
  
  CONCLUSIONS:
  This pilot study showed the feasibility of olfactory evaluation as a minimally invasive cognitive impairment assessment. The test can be used in logistically difficult environments, adding scientific value to this promising method. Although olfaction decreased after prolonged physical activity, further studies are warranted to make the relationship between cognition and external factors (eg, sleep deprivation, dehydration) more clear.
  
  Copyright © 2016 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.
  
  Guarda su PubMed

• Effects of Mountain Ultra-Marathon Running on ROS Production and Oxidative Damage by Micro-Invasive Analytic Techniques.
  PLoS One

  2015 ;10(11):e0141780. doi: e0141780.
  
  Mrakic-Sposta Simona, Gussoni Maristella, Moretti Sarah, Pratali Lorenza, Giardini Guido, Tacchini Philippe, Dellanoce Cinzia, Tonacci Alessandro, Mastorci Francesca, Borghini Andrea, Montorsi Michela, Vezzoli Alessandra
  
  Abstract
  
  PURPOSE:
  Aiming to gain a detailed insight into the physiological mechanisms involved under extreme conditions, a group of experienced ultra-marathon runners, performing the mountain Tor des Géants® ultra-marathon: 330 km trail-run in Valle d'Aosta, 24000 m of positive and negative elevation changes, was monitored. ROS production rate, antioxidant capacity, oxidative damage and inflammation markers were assessed, adopting micro-invasive analytic techniques.
  
  METHODS:
  Forty-six male athletes (45.04±8.75 yr, 72.6±8.4 kg, 1.76±0.05 m) were tested. Capillary blood and urine were collected before (Pre-), in the middle (Middle-) and immediately after (Post-) Race. Samples were analyzed for: Reactive Oxygen Species (ROS) production by Electron Paramagnetic Resonance; Antioxidant Capacity by Electrochemistry; oxidative damage (8-hydroxy-2-deoxy Guanosine: 8-OH-dG; 8-isoprostane: 8-isoPGF2?) and nitric oxide metabolites by enzymatic assays; inflammatory biomarkers (plasma and urine interleukin-6: IL-6-P and IL-6-U) by enzyme-linked immunosorbent assays (ELISA); Creatinine and Neopterin by HPLC, hematologic (lactate, glucose and hematocrit) and urine parameters by standard analyses.
  
  RESULTS:
  Twenty-five athletes finished the race, while twenty-one dropped out of it. A significant increase (Post-Race vs Pre) of the ROS production rate (2.20±0.27 vs 1.65±0.22 ?mol.min-1), oxidative damage biomarkers (8-OH-dG: 6.32±2.38 vs 4.16±1.25 ng.mg-1 Creatinine and 8-isoPGF2?: 1404.0±518.30 vs 822.51±448.91 pg.mg-1Creatinine), inflammatory state (IL-6-P: 66.42±36.92 vs 1.29±0.54 pg.mL-1 and IL-6-U: 1.33±0.56 vs 0.71±0.17 pg.mL1) and lactate production (+190%), associated with a decrease of both antioxidant capacity (-7%) and renal function (i.e. Creatinine level +76%) was found.
  
  CONCLUSIONS:
  The used micro-invasive analytic methods allowed us to perform most of them before, during and immediately after the race directly in the field, by passing the need of storing and transporting samples for further analysis. Considered altogether the investigated variables showed up that exhaustive and prolonged exercise not only promotes the generation of ROS but also induces oxidative stress, transient renal impairment and inflammation.
  
  Guarda su PubMed

• Training effects on ROS production determined by electron paramagnetic resonance in master swimmers.
  Oxid Med Cell Longev

  2015 ;2015():804794. doi: 804794.
  
  Mrakic-Sposta Simona, Gussoni Maristella, Porcelli Simone, Pugliese Lorenzo, Pavei Gaspare, Bellistri Giuseppe, Montorsi Michela, Tacchini Philippe, Vezzoli Alessandra
  
  Abstract
  
  Acute exercise induces an increase in Reactive Oxygen Species (ROS) production dependent on exercise intensity with highest ROS amount generated by strenuous exercise. However, chronic repetition of exercise, that is, exercise training, may reduce exercise-induced oxidative stress. Aim of this study was to evaluate the effects of 6-weeks high-intensity discontinuous training (HIDT), characterized by repeated variations of intensity and changes of redox potential, on ROS production and antioxidant capacity in sixteen master swimmers. Time course changes of ROS generation were assessed by Electron Paramagnetic Resonance in capillary blood by a microinvasive approach. An incremental arm-ergometer exercise (IE) until exhaustion was carried out at both before (PRE) and after (POST) training (Trg) period. A significant (P
  Guarda su PubMed

• A quantitative method to monitor reactive oxygen species production by electron paramagnetic resonance in physiological and pathological conditions.
  Oxid Med Cell Longev

  2014 ;2014():306179. doi: 306179.
  
  Mrakic-Sposta Simona, Gussoni Maristella, Montorsi Michela, Porcelli Simone, Vezzoli Alessandra
  
  Abstract
  
  The growing interest in the role of Reactive Oxygen Species (ROS) and in the assessment of oxidative stress in health and disease clashes with the lack of consensus on reliable quantitative noninvasive methods applicable. The study aimed at demonstrating that a recently developed Electron Paramagnetic Resonance microinvasive method provides direct evidence of the "instantaneous" presence of ROS returning absolute concentration levels that correlate with "a posteriori" assays of ROS-induced damage by means of biomarkers. The reliability of the choice to measure ROS production rate in human capillary blood rather than in plasma was tested (step I). A significant (P
  Guarda su PubMed

• Time-course changes of oxidative stress response to high-intensity discontinuous training versus moderate-intensity continuous training in masters runners.
  PLoS One

  2014 ;9(1):e87506. doi: e87506.
  
  Vezzoli Alessandra, Pugliese Lorenzo, Marzorati Mauro, Serpiello Fabio Rubens, La Torre Antonio, Porcelli Simone
  
  Abstract
  
  Beneficial systemic effects of regular physical exercise have been demonstrated to reduce risks of a number of age-related disorders. Antioxidant capacity adaptations are amongst these fundamental changes in response to exercise training. However, it has been claimed that acute physical exercise performed at high intensity (>60% of maximal oxygen uptake) may result in oxidative stress, due to reactive oxygen species being generated excessively by enhanced oxygen consumption. The aim of this study was to evaluate the effect of high-intensity discontinuous training (HIDT), characterized by repeated variations of intensity and changes of redox potential, on oxidative damage. Twenty long-distance masters runners (age 47.8 ± 7.8 yr) on the basis of the individual values of gas exchange threshold were assigned to a different 8-weeks training program: continuous moderate-intensity training (MOD, n = 10) or HIDT (n = 10). In both groups before (PRE) and after (POST) training we examined the following oxidative damage markers: thiobarbituric acid reactive substances (TBARS) as marker of lipid peroxidation; protein carbonyls (PC) as marker of protein oxidation; 8-hydroxy-2-deoxy-guanosine (8-OH-dG) as a biomarker of DNA base modifications; and total antioxidant capacity (TAC) as indicator of the overall antioxidant system. Training induced a significant (p
  Guarda su PubMed

• Structure-function paradigm in human myoglobin: how a single-residue substitution affects NO reactivity at low pO2.
  J Am Chem Soc

  2013 May;135(20):7534-44. doi: 10.1021/ja400213t.
  
  Scorciapino Mariano Andrea, Spiga Enrico, Vezzoli Alessandra, Mrakic-Sposta Simona, Russo Rosaria, Fink Bruno, Casu Mariano, Gussoni Maristella, Ceccarelli Matteo
  
  Abstract
  
  This work is focused on the two more expressed human myoglobin isoforms. In the literature, their different overexpression in high-altitude natives was proposed to be related to alternative/complementary functions in hypoxia. Interestingly, they differ only at residue-54, lysine or glutamate, which is external and far from the main binding site. In order to ascertain whether these two almost identical myoglobins might exert different functions and to contribute to a deeper understanding about myoglobin's oxygen-level dependent functioning, they have been compared with respect to dynamics, heme electronic structure, and NO reactivity at different O2 levels. Electron paramagnetic resonance (EPR) spectroscopy was employed to investigate the electronic structure of the nitrosyl-form, obtaining fundamental clues about a different bond interaction between the heme-iron and the proximal histidine and highlighting striking differences in NO reactivity, especially at a very low pO2. The experimental results well matched with the information provided by molecular dynamics simulations, which showed a significantly different dynamics for the two proteins only in the absence of O2. The single mutation differentiating the two myoglobins resulted in strongly affecting the plasticity of the CD-region (C-helix-loop-D-helix), whose fluctuations, being coupled to the solvent, were found to be correlated with the dynamics of the distal binding site. In the absence of O2, on the one hand a significantly different probability for the histidine-gate opening has been shown by MD simulations, and on the other a different yield of myoglobin-NO formation was experimentally observed through EPR.
  
  Guarda su PubMed

• Assessment of a standardized ROS production profile in humans by electron paramagnetic resonance.
  Oxid Med Cell Longev

  2012 ;2012():973927. doi: 973927.
  
  Mrakic-Sposta Simona, Gussoni Maristella, Montorsi Michela, Porcelli Simone, Vezzoli Alessandra
  
  Abstract
  
  Despite the growing interest in the role of reactive oxygen species (ROS) in health and disease, reliable quantitative noninvasive methods for the assessment of oxidative stress in humans are still lacking. EPR technique, coupled to a specific spin probe (CMH: 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine) is here presented as the method of choice to gain a direct measurement of ROS in biological fluids and tissues. The study aimed at demonstrating that, differently from currently available "a posteriori" assays of ROS-induced damage by means of biomolecules (e.g., proteins and lipids) spin-trapping EPR provides direct evidence of the "instantaneous" presence of radical species in the sample and, as signal areas are proportional to the number of excited electron spins, lead to absolute concentration levels. Using a recently developed bench top continuous wave system (e-scan EPR scanner, Bruker) dealing with very low ROS concentration levels in small (50 ?L) samples, we successfully monitored rapid ROS production changes in peripheral blood of athletes after controlled exercise and sedentary subjects after antioxidant supplementation. The correlation between EPR results and data obtained by various enzymatic assays (e.g., protein carbonyls and thiobarbituric acid reactive substances) was determined too. Synthetically, our method allows reliable, quick, noninvasive quantitative determination of ROS in human peripheral blood.
  
  Guarda su PubMed

• Fast reduction of peripheral blood endothelial progenitor cells in healthy humans exposed to acute systemic hypoxia.
  J Physiol

  2012 Feb;590(3):519-32. doi: 10.1113/jphysiol.2011.223032.
  
  Colombo Elena, Marconi Claudio, Taddeo Adriano, Cappelletti Monica, Villa Maria Luisa, Marzorati Mauro, Porcelli Simone, Vezzoli Alessandra, Della Bella Silvia
  
  Abstract
  
  There are hints that hypoxia exposure may affect the number of circulating endothelial progenitor cells (EPCs) in humans. To test this hypothesis, the concentration of EPCs was determined by flow cytometry in the peripheral blood of 10 young healthy adults before (0 h), at different times (0.5 h, 1 h, 2 h and 4 h) during a 4 h normobaric hypoxic breathing simulating 4100 m altitude, and in the following recovery breathing room air. Results were interpreted mainly on the basis of the changes in surface expression of CXC chemokine receptor-4 (CXCR-4, a chemokine receptor essential for EPC migration and homing) and the percentage of apoptotic cells, the plasmatic levels of markers of oxidative stress induced by hypoxic breathing. Compared to 0 h, the concentration of EPCs, identified as either CD45(dim)/CD34(+)/KDR(+) or CD45(dim)/CD34(+)/KDR(+)/CD133(+) cells, decreased from 337 ± 83 ml(-1) (mean ± SEM) to 223 ± 52 ml(-1) (0.5 h; P
  Guarda su PubMed

• Structural characterization of recombinant human myoglobin isoforms by (1)H and (129)Xe NMR and molecular dynamics simulations.
  Biochim Biophys Acta

  2011 Dec;1814(12):1919-29. doi: 10.1016/j.bbapap.2011.06.014.
  
  Gussoni Maristella, Scorciapino Mariano Andrea, Vezzoli Alessandra, Anedda Roberto, Greco Fulvia, Ceccarelli Matteo, Casu Mariano
  
  Abstract
  
  Myoglobin (Mb), the main cytosolic oxygen storage/deliver protein, is also known to interact with different small ligands exerting other fundamental physiological roles. In Humans up to five different Mb isoforms are present. The two most expressed ones (>90%) differ only at the 54th position, K54 (Mb-I) and E54 (Mb-II) respectively. High-altitude populations are characterized by a higher Mb concentration in skeletal muscle, totally attributable to Mb-II, as well as a higher efficiency of locomotion, leading to the hypothesis of a cause-effect relationship with the evolutionary response to the high-altitude hypoxic environment. In this work, a first structural characterization of the two more expressed human Mb isoforms has been carried out. In particular, a detailed (1)H and (129)Xe NMR study was aimed to characterize the structure of the hydrophobic cavities around the heme group. Experimental results have been compared to those from MD simulations, i.e. volume fluctuations and occurrence. Electronic structure of the heme ring ground state resulted to be comparable for the two investigated isoforms, despite the single point mutation at position 54. However, the use of (129)Xe as a probe revealed small but significant modifications in the structure of internal cavities. MD simulations supported NMR results indicating interesting structural/dynamical differences in the average volume and occurrence of the main cavities lining Mb prosthetic group.
  
  Copyright © 2011 Elsevier B.V. All rights reserved.
  
  Guarda su PubMed

• A quantitative method to assess muscle tissue oxygenation in vivo by monitoring 1H nuclear magnetic resonance myoglobin resonances.
  Anal Biochem

  2010 May;400(1):33-45. doi: 10.1016/j.ab.2010.01.022.
  
  Gussoni Maristella, Cremonini Mauro A, Vezzoli Alessandra, Greco Fulvia, Zetta Lucia
  
  Abstract
  
  A nuclear magnetic resonance (NMR) method was implemented to assess in vivo oxygenation levels by a quantitative determination of the 1H NMR myoglobin (Mb) resonances. The proximal His-F8 NdeltaH at 70-90 ppm and Val-E11 gammaCH3 resonance at -2.8 ppm, reflecting deoxygenated (deoxy-Mb) and oxygenated (met-Mb) states, were alternately recorded. The method was developed in vitro choosing a couple of NMR sequences that could each maximize the signal-to-noise ratio (SNR) while avoiding baseline rolling and suppressing the water signal. Two quantitative calibration methods were implemented for deoxy- and met-Mb samples (0.1-1 mM), respectively. The respective limit of detection (LOD) and limit of quantification (LOQ) were 0.015 and 0.05 mM for met-Mb and 0.013 and 0.042 mM for deoxy-Mb. Sequences and calibration curves were employed in vivo in Arenicola marina to obtain, for the first time, an accurate measurement of oxy- and deoxy-Mb actual concentrations. In Arenicola, the peaks at approximately 87 and -2.7 ppm, reflecting the deoxy- and oxy-Mb states, respectively, were alternately recorded during increasing hypoxia. The deoxy-Mb concentrations were obtained from the calibration curve. The oxy-Mb concentrations were calculated from the calibration of met-Mb because it was proved that oxy- and met-Mb gave the same NMR molar response. From oxy- and deoxy-Mb concentrations, the intracellular oxygen partial pressure (PiO2) trend was determined.
  
  2010 Elsevier Inc. All rights reserved.
  
  Guarda su PubMed

• Osmotic and aging effects in caviar oocytes throughout water and lipid changes assessed by 1H NMR T1 and T2 relaxation and MRI.
  Magn Reson Imaging

  2007 Jan;25(1):117-28.
  
  Gussoni Maristella, Greco Fulvia, Vezzoli Alessandra, Paleari Maria Antonietta, Moretti Vittorio Maria, Lanza Barbara, Zetta Lucia
  
  Abstract
  
  By combining NMR relaxation spectroscopy and magnetic resonance imaging techniques, unsalted (us) and salted (s) caviar (Acipenser transmontanus) oocytes were characterized over a storage period of up to 90 days. The aging and the salting effects on the two major cell constituents, water and lipids, were separately assessed. T1 and T2 decays were interpreted by assuming a two-site exchange model. At Day 0, two water compartments that were not in fast exchange were identified by the T1 relaxation measurements on the us oocytes. In the s samples, T1 decay was monoexponential. During the time of storage, an increment of the free water amount was found for the us oocytes, ascribed to an increased metabolism. T1 and T2 of the s oocytes shortened as a consequence of the osmotic stress produced by salting. Selective images showed the presence of water endowed with different regional mobility that severely changed during the storage. Lipid T1 relaxation decays collected on us and s samples were found to be biexponential, and the T1 values lengthened during storage. In us and s oocytes, the increased lipid mobility with the storage was ascribed to lipolysis. Selective images of us samples showed lipids that were confined to the cytoplasm for up to 60 days of storage.
  
  Guarda su PubMed

• Monitoring the effects of storage in caviar from farmed Acipenser transmontanus using chemical, SEM, and NMR methods.
  J Agric Food Chem

  2006 Sep;54(18):6725-32.
  
  Gussoni Maristella, Greco Fulvia, Vezzoli Alessandra, Paleari Maria Antonietta, Moretti Vittorio Maria, Beretta Giuseppe, Caprino Fabio, Lanza Barbara, Zetta Lucia
  
  Abstract
  
  The effects of storage at 4 degrees C on the quantity and quality of chemical components in the caviar from farmed Acipenser transmontanus have been analyzed by SEM, chemical methods, and NMR and MRI techniques. Particular attention has been focused on the lipid components, the distribution and mobility of which were strongly affected by the storage time. MRI and relaxation data indicated that lipids are endowed with two different mobility regimes, one slow (short T1) and one fast (long T1), both lengthening with the storage time. Chemical analysis assessed a total fat content that remained practically unchanged and a constant fatty acid composition during the total storage time. The combination of the two methods allowed one (a) to suppose that a mechanism of lipid hydrolysis (faster in unsalted than in salted eggs) is still occurring during storage of caviar at 4 degrees C for up to approximately 4 months and (b) to exclude that an intensive oxidative process is active in the same storage period.
  
  Guarda su PubMed

• Temperature and pH dependence of energy balance by (31)P- and (1)H-MRS in anaerobic frog muscle.
  Biochim Biophys Acta

  2004 Feb;1608(2-3):163-70.
  
  Vezzoli Alessandra, Gussoni Maristella, Greco Fulvia, Zetta Lucia, Cerretelli Paolo
  
  Abstract
  
  The temperature (T)-dependence of energy consumption of resting anaerobic frog gastrocnemii exposed to different, changing electrochemical gradients was assessed. To this aim, the rate of ATP resynthesis (delta approximately P/deltat) was determined by (31)P- and (1)H-MRS as the sum of the rates of PCr hydrolysis (delta[PCr]/deltat) and of anaerobic glycolysis (delta[La]/ deltat, based on a approximately P/La ratio of 1.5). The investigated T levels were 15, 20 and 25 degrees C, whereas initial extracellular pH (pHe) values were 7.9, 7.3 and 7.0, i.e. higher, equal or lower, respectively, than intracellular pH (pHi). The latter was changing with T according to the neutrality point (dpH/dT=-0.0165 pH units/ degrees C). Both rates of PCr hydrolysis and of lactate accumulation and that of their sum, expressed as delta approximately P/deltat, were highly T-dependent. By contrast, the pHe-dependence of the muscle energy balance was nil or extremely limited at 15 and 20 degrees C, respectively, but remarkable at 25 degrees C (with a depression of the ATP resynthesis rate up to 25% with a decrease of pHe from 7.9 to 7.0). The pHe-dependent reduction of metabolic rate was associated with a down-regulation of anaerobic glycolysis due to reduced activity of ion-transporters controlling acid-base balance and/or to a shift from Na(+)/H(+) to a more efficient Na(+)-dependent Cl(-)/HCO(3)(-) exchanger. Uncoupling of glycogenolysis from P-metabolite concentrations, both as function of T (>or=20 degrees C) and of pHe (
  Guarda su PubMed

• Effects of temperature and extracellular pH on metabolites: kinetics of anaerobic metabolism in resting muscle by 31P- and 1H-NMR spectroscopy.
  J Exp Biol

  2003 Sep;206(Pt 17):3043-52.
  
  Vezzoli Alessandra, Gussoni Maristella, Greco Fulvia, Zetta Lucia
  
  Abstract
  
  Environmental stress, such as low temperature, extracellular acidosis and anoxia, is known to play a key role in metabolic regulation. The aim of the present study was to gain insight into the combined temperature-pH regulation of metabolic rate in frog muscle, i.e. an anoxia-tolerant tissue. The rate of exergonic metabolic processes occurring in resting isolated muscles was determined at 15 degrees C and 25 degrees C as well as at extracellular pH values higher (7.9), similar (7.3) and lower (7.0) than the physiological intracellular pH. (31)P and (1)H nuclear magnetic resonance spectroscopy high-resolution measurements were carried out at 4.7 T in isolated frog (Rana esculenta) gastrocnemius muscle during anoxia to assess, by means of reference compounds, the concentration of all phosphate metabolites and lactate. Intra- and extracellular pH was also determined. In the range of examined temperatures (15-25 degrees C), the temperature dependence of anaerobic glycolysis was found to be higher than that of PCr depletion (Q(10)=2.3). High-energy phosphate metabolism was confirmed to be the initial and preferential energy source. The rate of phosphocreatine hydrolysis did not appear to be affected by extracellular pH changes. By contrast, independent of the intracellular pH value, at the higher temperature (25 degrees C) a lowering of the extracellular pH from 7.9 to 7.0 caused a depression in lactate accumulation. This mechanism was ascribed to the transmembrane proton concentration gradient. This parameter was demonstrated to regulate glycolysis, probably through a reduced lactate efflux, depending on the activity of the lactate-H(+) co-transporter. The calculated intracellular buffer capacity was related to intra- and extracellular pH and temperature. At the experimental extracellular pH of 7.9 and at a temperature of 15 degrees C and 25 degrees C, calculated intracellular buffering capacity was 29.50 micromol g(-1) pH unit(-1) and 69.98 micromol g(-1) pH unit(-1), respectively.
  
  Guarda su PubMed