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Oxylipins are powerful signalling compounds derived from polyunsaturated fatty acids (PUFAs) and involved in regulating the immune system response. A mass spectrometry-based method was developed and validated for the targeted profiling of 52 oxylipins (e.g., isoprostanoids, prostaglandins, epoxy- and hydroxy-fatty acids, specialized pro-resolving mediators) and 4 PUFAs in small urinary extracellular vesicles (uEVs). Ultrasound-assisted extraction using a 50:50 v/v MeOH:H2O mixture ensured optimal analytical performances. Limits of detection ranged between 10 and 400 pg/mL for oxylipins and 0.10-3 ng/mL for PUFAs. Satisfactory recoveries (85-116 %) and good intra- and inter-day precisions (RSD ≤15 %) were obtained for all the analytes. The reliability of the procedure was tested in a real case scenario by monitoring ultramarathon runners during the world Tor des Géants® (TDG) race. Both F2- and E2-isoprostanes were detected in small uEVs of the ultramarathon runners, suggesting the onset of an oxidant insult. 5-F2t-IsoP exhibited significant pre- to post-race variations, thus potentially representing a non-invasive marker of in-vivo lipid peroxidation. The presence of specialized pro-resolving mediators suggests the activation of pro-resolution signalling cascade resolving inflammation. These outcomes may help manage post-exercise recovery and improve training.
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Introduction: Diving decompression theory hypothesizes inflammatory processes as a source of micronuclei which could increase related risks. Therefore, we tested 10 healthy, male divers. They performed 6-8 dives with a maximum of two dives per day at depths ranging from 21 to 122 msw with CCR mixed gas diving. Methods: Post-dive VGE were counted by echocardiography. Saliva and urine samples were taken before and after each dive to evaluate inflammation: ROS production, lipid peroxidation (8-iso-PGF2), DNA damage (8-OH-dG), cytokines (TNF-α, IL-6, and neopterin). Results: VGE exhibits a progressive reduction followed by an increase (p < 0.0001) which parallels inflammation responses. Indeed, ROS, 8-iso-PGF2, IL-6 and neopterin increases from 0.19 ± 0.02 to 1.13 ± 0.09 µmol.min-1 (p < 0.001); 199.8 ± 55.9 to 632.7 ± 73.3 ng.mg-1 creatinine (p < 0.0001); 2.35 ± 0.54 to 19.5 ± 2.96 pg.mL-1 (p < 0.001); and 93.7 ± 11.2 to 299 ± 25.9 µmol·mol-1 creatinine (p = 0.005), respectively. The variation after each dive was held constant around 158.3% ± 6.9% (p = 0.021); 151.4% ± 5.7% (p < 0.0001); 176.3% ± 11.9% (p < 0.0001); and 160.1% ± 5.6% (p < 0.001), respectively. Discussion: When oxy-inflammation reaches a certain level, it exceeds hormetic coping mechanisms allowing second-generation micronuclei substantiated by an increase of VGE after an initial continuous decrease consistent with a depletion of "first generation" pre-existing micronuclei.
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Underwater activities are characterized by an imbalance between reactive oxygen/nitrogen species (RONS) and antioxidant mechanisms, which can be associated with an inflammatory response, depending on O2 availability. This review explores the oxidative stress mechanisms and related inflammation status (Oxy-Inflammation) in underwater activities such as breath-hold (BH) diving, Self-Contained Underwater Breathing Apparatus (SCUBA) and Closed-Circuit Rebreather (CCR) diving, and saturation diving. Divers are exposed to hypoxic and hyperoxic conditions, amplified by environmental conditions, hyperbaric pressure, cold water, different types of breathing gases, and air/non-air mixtures. The "diving response", including physiological adaptation, cardiovascular stress, increased arterial blood pressure, peripheral vasoconstriction, altered blood gas values, and risk of bubble formation during decompression, are reported.
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Buceo , Oxígeno , Humanos , Buceo/fisiología , Nitrógeno , Hipoxia , InflamaciónRESUMEN
Long COVID-19 patients show systemic inflammation and persistent symptoms such as fatigue and malaise, profoundly affecting their quality of life. Since improving oxygenation can oppose inflammation at multiple tissue levels, we hypothesized that hyperbaric oxygen therapy (HBOT) could arrest inflammation progression and thus relieve symptoms of COVID-19. We evaluated oxy-inflammation biomarkers in long COVID-19 subjects treated with HBOT and monitored with non-invasive methods. Five subjects (two athletes and three patients with other comorbidities) were assigned to receive HBOT: 100% inspired O2 at 2.4 ATA in a multiplace hyperbaric chamber for 90 min (three athletes: 15 HBOT × 5 days/wk for 3 weeks; two patients affected by Idiopathic Sudden Sensorineural Hearing Loss: 30 HBOT × 5 days/wk for 6 weeks; and one patient with osteomyelitis: 30 HBOT × 5 days/wk for week for 6 weeks and, after a 30-day break, followed by a second cycle of 20 HBOT). Using saliva and/or urine samples, reactive oxygen species (ROS), antioxidant capacity, cytokines, lipids peroxidation, DNA damage, and renal status were assessed at T1_pre (basal level) and at T2_pre (basal level after treatment), and the results showed attenuated ROS production, lipid peroxidation, DNA damage, NO metabolites, and inflammation biomarker levels, especially in the athletes post-treatment. Thus, HBOT may represent an alternative non-invasive method for treating long COVID-19-induced long-lasting manifestations of oxy-inflammation.
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Intense, long exercise can increase oxidative stress, leading to higher levels of inflammatory mediators and muscle damage. At the same time, fatigue has been suggested as one of the factors giving rise to delayed-onset muscle soreness (DOMS). The aim of this study was to investigate the efficacy of a specific electrical stimulation (ES) treatment (without elicited muscular contraction) on two different scenarios: in the laboratory on eleven healthy volunteers (56.45 ± 4.87 years) after upper limbs eccentric exercise (Study 1) and in the field on fourteen ultra-endurance athletes (age 47.4 ± 10.2 year) after an ultra-running race (134 km, altitude difference of 10,970 m+) by lower exercising limbs (Study 2). Subjects were randomly assigned to two experimental tasks in cross-over: Active or Sham ES treatments. The ES efficacy was assessed by monitoring the oxy-inflammation status: Reactive Oxygen Species production, total antioxidant capacity, IL-6 cytokine levels, and lactate with micro-invasive measurements (capillary blood, urine) and scales for fatigue and recovery assessments. No significant differences (p > 0.05) were found in the time course of recovery and/or pre-post-race between Sham and Active groups in both study conditions. A subjective positive role of sham stimulation (VAS scores for muscle pain assessment) was reported. In conclusion, the effectiveness of ES in treating DOMS and its effects on muscle recovery remain still unclear.
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Hyperbaric oxygen therapy (HBOT) is a therapeutical approach based on exposure to pure oxygen in an augmented atmospheric pressure. Although it has been used for years, the exact kinetics of the reactive oxygen species (ROS) between different pressures of hyperbaric oxygen exposure are still not clearly evidenced. In this study, the metabolic responses of hyperbaric hyperoxia exposures for 1 h at 1.4 and 2.5 ATA were investigated. Fourteen healthy non-smoking subjects (2 females and 12 males, age: 37.3 ± 12.7 years old (mean ± SD), height: 176.3 ± 9.9 cm, and weight: 75.8 ± 17.7 kg) volunteered for this study. Blood samples were taken before and at 30 min, 2 h, 24 h, and 48 h after a 1 h hyperbaric hyperoxic exposure. The level of oxidation was evaluated by the rate of ROS production, nitric oxide metabolites (NOx), and the levels of isoprostane. Antioxidant reactions were assessed through measuring superoxide dismutase (SOD), catalase (CAT), cysteinylglycine, and glutathione (GSH). The inflammatory response was measured using interleukine-6, neopterin, and creatinine. A short (60 min) period of mild (1.4 ATA) and high (2.5 ATA) hyperbaric hyperoxia leads to a similar significant increase in the production of ROS and antioxidant reactions. Immunomodulation and inflammatory responses, on the contrary, respond proportionally to the hyperbaric oxygen dose. Further research is warranted on the dose and the inter-dose recovery time to optimize the potential therapeutic benefits of this promising intervention.
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Oxigenoterapia Hiperbárica , Hiperoxia , Masculino , Femenino , Humanos , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/metabolismo , Cinética , Oxígeno , Estrés Oxidativo/fisiologíaRESUMEN
PURPOSE: To evaluate the changes in gustatory and olfactory sensitivity and dietary habits between healthy lean subjects (LS) and participants affected by overweight (OW), stage I and II obesity and to estimate possible impact of these factors on body mass index (BMI). METHODS: After a general and ear-nose-throat evaluation, taste and olfactory function testing by means of taste strips and sniffin' stick tests, respectively, and food habits analysis by means of food frequency questionnaire (FFQ), 221 participants (68 LS [33 female; mean age = 53.01 ± 7.54 years]; 51 OW [26 female; mean age = 51.5 ± 12.16 years]; 50 stage I obesity [24 female; mean age = 50.78 ± 13.71 years] and 52 stage II obesity [24 female; mean age = 52.21 ± 13.35 years]) were enrolled in the study. RESULTS: Significant (p < 0.008) reductions in total and subtest taste and smell scores were found in stage I and II obesity when compared to LS and OW participants. FFQ depicted a progressive intake increase of nutrients along the BMI stages. Significant associations were found between BMI and taste/smell subtests sugar taste carbs, saturated, monounsaturated and polyunsaturated fatty acids. CONCLUSIONS: These data demonstrated for the first time a parallel impairment in smell and taste in a large sample size of participants from lean to stage II obesity and could reinforce those previous theories claiming that the greater the ability in taste or smell qualities perception, the lower the preference for them, resulting in a lower intake of specific foods.
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Olfato , Gusto , Humanos , Femenino , Persona de Mediana Edad , Adulto , Anciano , Índice de Masa Corporal , Conducta Alimentaria , Obesidad , SobrepesoRESUMEN
An imbalance of oxy-inflammation status has been involved in axonal damage and demyelination in multiple sclerosis (MS). The aim of this study was to investigate the efficacy of an antioxidant treatment (calcium disodium ethylenediaminetetracetic acid-EDTA) chelation therapy associated with a micronutrient complex in MS patients. A total of 20 MS patients and 20 healthy subjects, enrolled as a control group (CTR), were recruited. We measured the plasma ROS production and total antioxidant capacity (TAC) by a direct assessment using Electron Paramagnetic Resonance; activities of the antioxidant system (thiols' redox status and enzymes); and the urinary presence of biomarkers of oxidative stress by immunoenzymatic assays. We also evaluated the levels of inflammation by plasmatic cytokines (TNFα, IL-1ß, and IL-6) and assessed the sICAM levels, as well as the nitric oxide (NO) catabolism and transthyretin (TTR) concentration. Comparing CTR and MS, in the latter ROS production, oxidative damage, inflammatory biomarkers, and NO metabolite concentrations results were significantly higher, while TAC was significantly lower. Treatment in MS induced significant (p < 0.05) down-regulating of pro-inflammatory sICAM1, TNF-α, IL6, as well as biomarkers of lipid peroxidation and DNA damage production. The protective effect exhibited may occur by decreasing ROS production and increasing antioxidant capacity, turning into a more reduced thiols' status.
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In this study, the metabolic responses of hypoxic breathing for 1 h to inspired fractions of 10% and 15% oxygen were investigated. To this end, 14 healthy nonsmoking subjects (6 females and 8 males, age: 32.2 ± 13.3 years old (mean ± SD), height: 169.1 ± 9.9 cm, and weight: 61.6 ± 16.2 kg) volunteered for the study. Blood samples were taken before, and at 30 min, 2 h, 8 h, 24 h, and 48 h after a 1 h hypoxic exposure. The level of oxidative stress was evaluated by considering reactive oxygen species (ROS), nitric oxide metabolites (NOx), lipid peroxidation, and immune-inflammation by interleukin-6 (IL-6) and neopterin, while antioxidant systems were observed in terms of the total antioxidant capacity (TAC) and urates. Hypoxia abruptly and rapidly increased ROS, while TAC showed a U-shape pattern, with a nadir between 30 min and 2 h. The regulation of ROS and NOx could be explained by the antioxidant action of uric acid and creatinine. The kinetics of ROS allowed for the stimulation of the immune system translated by an increase in neopterin, IL-6, and NOx. This study provides insights into the mechanisms through which acute hypoxia affects various bodily functions and how the body sets up the protective mechanisms to maintain redox homeostasis in response to oxidative stress.
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Antioxidantes , Interleucina-6 , Masculino , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Antioxidantes/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Neopterin/metabolismo , Interleucina-6/metabolismo , Cinética , Estrés Oxidativo/fisiología , Hipoxia/metabolismo , Oxidación-ReducciónRESUMEN
Functional movement disorders (FMD) are characterized by the presence of neurological symptoms that cannot be explained by typical neurological diseases or other medical conditions. First evidence showed that, compared to healthy controls (CTR), FMD patients presented increased levels of glutamate+glutamine in the anterior cingulate cortex/medial prefrontal cortex, and decreased levels of glutamate in the cerebrospinal fluid, suggesting that a glutamatergic dysfunction might play a role in FMD pathophysiology. In this study, 12 FMD patients and 20 CTR were recruited and underwent venous blood sampling and urine collection: levels of glutamate, BDNF, dopamine, oxidative stress, creatinine, neopterin, and uric acid were analyzed. Participants also underwent a psychometric assessment investigating depression, anxiety, and alexithymia. We found that levels of glutamate, BDNF, and dopamine were significantly lower in the blood of FMD patients than CTR. Glutamate and dopamine levels were positively associated with levels of alexithymia. Our findings give further evidence that glutamatergic dysfunction might be involved in the pathophysiology of FMD, possibly representing a biomarker of disease; moreover, since glutamatergic and dopaminergic systems are closely interconnected, our results might have a relevance in terms of treatment options for FMD patients.
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Trastornos de Conversión , Dopamina , Humanos , Factor Neurotrófico Derivado del Encéfalo , Ácido Glutámico , Plasticidad Neuronal , GlutaminaRESUMEN
Differences in gustatory sensitivity, nutritional habits, circulating levels of modulators, anthropometric measures, and metabolic assays may be involved in overweight (OW) development. The present study aimed at evaluating the differences in these aspects between 39 OW (19 female; mean age = 53.51 ± 11.17), 18 stage I (11 female; mean age = 54.3 ± 13.1 years), and 20 II (10 female; mean age = 54.5 ± 11.9) obesity participants when compared with 60 lean subjects (LS; 29 female; mean age = 54.04 ± 10.27). Participants were evaluated based on taste function scores, nutritional habits, levels of modulators (leptin, insulin, ghrelin, and glucose), and bioelectrical impedance analysis measurements. Significant reductions in total and subtests taste scores were found between LS and stage I and II obesity participants. Significant reductions in total and all subtests taste scores were found between OW and stage II obesity participants. Together with the progressive increase in plasmatic leptin levels, insulin, and serum glucose, decrease in plasmatic ghrelin levels, and changes in anthropometric measures and nutritional habits along with body mass index, these data for the first time demonstrated that taste sensitivity, biochemical regulators, and food habits play a parallel, concurring role along the stages evolving to obesity.
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Conducta Alimentaria , Obesidad , Sobrepeso , Gusto , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Índice de Masa Corporal , Ghrelina , Glucosa , Insulina , Leptina , Obesidad/metabolismo , Sobrepeso/metabolismo , MasculinoRESUMEN
Exposure to acute normobaric hypoxia (NH) elicits reactive oxygen species (ROS) accumulation, whose production kinetics and oxidative damage were here investigated. Nine subjects were monitored while breathing an NH mixture (0.125 FIO2 in air, about 4100 m) and during recovery with room air. ROS production was assessed by Electron Paramagnetic Resonance in capillary blood. Total antioxidant capacity, lipid peroxidation (TBARS and 8-iso-PFG2α), protein oxidation (PC) and DNA oxidation (8-OH-dG) were measured in plasma and/or urine. The ROS production rate (µmol·min-1) was monitored (5, 15, 30, 60, 120, 240 and 300 min). A production peak (+50%) was reached at 4 h. The on-transient kinetics, exponentially fitted (t1/2 = 30 min r2 = 0.995), were ascribable to the low O2 tension transition and the mirror-like related SpO2 decrease: 15 min: -12%; 60 min: -18%. The exposure did not seem to affect the prooxidant/antioxidant balance. Significant increases in PC (+88%) and 8-OH-dG (+67%) at 4 h in TBARS (+33%) one hour after hypoxia offset were also observed. General malaise was described by most of the subjects. Under acute NH, ROS production and oxidative damage resulted in time and SpO2-dependent reversible phenomena. The experimental model could be suitable for evaluating the acclimatation level, a key element in the context of mountain rescues in relation to technical/medical workers who have not had enough time for acclimatization-as, for example, during helicopter flights.
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Antioxidantes , Hipoxia , Humanos , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/metabolismo , 8-Hidroxi-2'-Desoxicoguanosina , Sustancias Reactivas al Ácido Tiobarbitúrico , Hipoxia/metabolismo , Oxígeno/metabolismo , AltitudRESUMEN
Freeskiing is performed in an extreme environment, with significant physical effort that can induce reactive oxygen species (ROS) generation and dehydration. This study aimed to investigate the evolution of the oxy-inflammation and hydration status during a freeskiing training season with non-invasive methods. Eight trained freeskiers were investigated during a season training: T0 (beginning), T1-T3 (training sessions), and T4 (after the end). Urine and saliva were collected at T0, before (A) and after (B) T1-T3, and at T4. ROS, total antioxidant capacity (TAC), interleukin-6 (IL-6), nitric oxide (NO) derivatives, neopterin, and electrolyte balance changes were investigated. We found significant increases in ROS generation (T1A-B +71%; T2A-B +65%; T3A-B +49%; p < 0.05-0.01) and IL-6 (T2A-B +112%; T3A-B +133%; p < 0.01). We did not observe significant variation of TAC and NOx after training sessions. Furthermore, ROS and IL-6 showed statistically significant differences between T0 and T4 (ROS +48%, IL-6 +86%; p < 0.05). Freeskiing induced an increase in ROS production, which can be contained by antioxidant defense activation, and in IL-6, as a consequence of physical activity and skeletal muscular contraction. We did not find deep changes in electrolytes balance, likely because all freeskiers were well-trained and very experienced.
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Antioxidantes , Estrés Oxidativo , Humanos , Antioxidantes/metabolismo , Especies Reactivas de Oxígeno , Estrés Oxidativo/fisiología , Proyectos Piloto , Estaciones del Año , Interleucina-6 , InflamaciónRESUMEN
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.
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Disfunción Cognitiva , Buceo , Narcosis por Gas Inerte , Estupor , Humanos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Disfunción Cognitiva/etiología , Descompresión/efectos adversos , Buceo/efectos adversos , Dopamina/metabolismo , Glutamatos , Narcosis por Gas Inerte/complicaciones , Especies Reactivas de Oxígeno , Estupor/etiologíaRESUMEN
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.
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Obesidad , Trastornos del Olfato , Adulto , Anciano , Femenino , Ghrelina , Humanos , Factor I del Crecimiento Similar a la Insulina , Insulinas , Leptina , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Odorantes , Trastornos del Olfato/diagnóstico , Trastornos del Olfato/etiología , OlfatoRESUMEN
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 O2 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 20th day) with a decrease in antioxidant capacity (peak 90th day: -52%). Results suggest that the adaptive response of oxidative stress balance to HH requires a relatively long time, more than 300th 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.
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Hipoxia , Estrés Oxidativo , Regiones Antárticas , Humanos , Oxígeno/farmacología , Especies Reactivas de Oxígeno/farmacologíaRESUMEN
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 24â 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.
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Drosophila melanogaster , Longevidad , Animales , Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Hipoxia/genética , Longevidad/genética , Masculino , Oxígeno/farmacología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
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 PGE2 (+120%) and 15-deoxy-delta12,14-PGJ2 (+233%). The isoprostane 15-F2t-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.
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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-PGF2α) and NO availability and metabolism (NO2, NOx and 3-NT and iNOS expression). Data from a dive breathing a hypoxic (16% O2 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.