Exercise-induced Oxidative Stress Research Articles

The Effect Of L-Carnitine And Alpha Lipoic Acid Administration With Exercise In Old Rats On Energy Metabolism Related To Oxidative Stress Parameters

Objective: This study aims to contribute novel insights by investigating the potential positive effects of a combined dietary supplement and exercise program on mitochondrial oxidative stress and energy metabolism in aging. Focusing on the protective impact of Alpha Lipoic Acid (ALA), a potent antioxidant, against exercise-induced mitochondrial oxidative stress in rats, we also assess how L-Carnitine administration affects exercise ability by analyzing resistin and HbA1c levels, indicators linked to insulin resistance and cellular sensitivity. Methods: In this 10-day study, 42 old male Sprague Dawley rats (weighing 400±10 g, aged 15–17 weeks) were divided into six groups (n=7): Control, Exercise, L-Carnitine, Alpha Lipoic Acid (ALA), L-Carnitine+Exercise, ALA+Exercise. Relevant groups received daily oral gavage doses of L- Carnitine (50 mg/ml) and ALA (18 mg/ml). Exercise groups underwent treadmill sessions. On day 10, blood samples were quantitatively analyzed for HbA1c and Resistin levels using a Cusabio ELISA assay kit (China). Results: ALA supplementation synergistically reduced resistin and HbA1c levels, individually and combined with exercise. Conversely, L-Carnitine supplement, alone or with exercise, increased resistin levels but it caused a decrease in HbA1c levels. Conclusions: The data indicated a minor, insignificant decrease in resistin levels for the exercise and ALA groups, with a statistically significant difference in HbA1c levels among all groups. Exercise alone positively impacted both HbA1c and resistin levels, suggesting a potential counteraction of age-related oxidative stress and a positive influence on energy metabolism through an appropriate diet and exercise program. Further studies are required to explore specific metabolic pathways and relationships identified in our findings.

Purple sweet potato antioxidants for oxidative stress caused by intense physical exercise

Background: Intense exercise increases ROS and reactive nitrogen species, leading to oxidative stress and potential health issues. Balancing free radical production and antioxidant defence is crucial. Endogenous antioxidants help neutralise ROS, but additional supplementation is required to prevent cell damage. Objective: This literature review explores the potential of purple sweet potato (Ipomoea batatas L.) as an antioxidant source to counteract exercise-induced oxidative stress. Method: Scientific articles from various platforms were collected using keywords such as "Physical exercise," "Oxidative stress," "Purple sweet potato," and "Antioxidant”. Result: Purple sweet potato, rich in anthocyanins and vitamin C, exhibits potent free radical scavenging properties. Consumption of purple sweet potato enhances superoxide dismutase (SOD) levels, reduces lipid peroxidation (MDA), inhibits the NF-kB signalling pathway, and prevents increased heat shock protein 72 (HSP72) expression. These findings suggest that purple sweet potato consumption promotes cellular health and mitigates oxidative stress caused by intense physical exercise. Conclusion: In conclusion, incorporating purple sweet potato into the diet shows promise in countering exercise-induced oxidative stress, promoting overall well-being, and preventing chronic diseases. Further research is needed to fully understand the mechanisms and optimal dosage for combating oxidative stress during rigorous physical training.

Ascorbic Acid Supplementation and Immune Response in Healthy Women during High-intensity Exercise

Introduction the benefits of consuming extra Ascorbic Acid (AA) while exercising are not well understood. Aim This study aims to explore the effects of AA supplementation on oxidative stress, the immunological response, and inflammation in healthy women after a single bout of high-intensity exercise. Materials and Methods In a crossover design, 20 sedentary women (aged 18-22) underwent 30 minutes of vigorous cycling. They were divided into two groups: one receiving daily 1,000 mg ascorbic acid supplementation (1,000AA) and the other without supplementation (0AA). This regimen was maintained for one week. Blood samples obtained pre-exercise, immediately post-exercise, and 24 hours post-exercise underwent analysis for oxidative stress, inflammatory markers, CD4+ and CD8+ lymphocytes, and neutrophil phagocytic activity. Results An AA supplement significantly increased plasma concentrations of AA (p<0.05) and reduced post-exercise plasma MDA levels (p<0.05) but did not affect creatine kinase activity. White blood cells, CD8+ T cells, and IL-6 increased significantly after exercise but remained unchanged in the 1,000AA group compared to the 0AA group, while the neutrophil count increased (p<0.05) after exercise with no change in phagocytic function. A slight drop in phagocytic function was observed 24 hours after exercise in the 1,000AA group. Exercise and AA supplements had no effect on CD4+ T cells. Conclusion a single session of high-intensity exercise caused oxidative stress, muscle injury, and inflammation, as well as a transient increase in CD8+ T cells. A short administration of AA attenuated the exercise-induced oxidative stress and reduced inflammation by limiting the increase in IL-6 and CD8+ T cells.

Oxidative Stress Impacts on Exercising of Skeletal Muscles

Reactive oxygen species (ROS) are known to be raised in skeletal muscle as a result of muscular contractions during exercise. These extremely reactive compounds have several harmful consequences, including decreased force production and higher muscular wasting. Numerous studies have shown that ROS generated during exercise also have beneficial benefits by altering cellular processes that result in enhanced expression of antioxidants, since the discovery of exercise-induced oxidative stress some decades ago. Evidence has mounted that the reactive oxygen species (ROS) generated during physical activity also yield benefits by modulating cellular mechanisms that result in elevated production of antioxidants. To neutralize free radicals and stop the harmful effects of reactive oxygen species (ROS), these molecules are specially raised in frequently exercising muscles. Furthermore, ROS appears to play a role in the adaptation of the muscle phenotypic brought on by exercise. An overview of the research to date on the effects of ROS during muscle exercise is given in this review. These elements include the origins of ROS, their cellular effects—both beneficial and detrimental—the function of antioxidants, and the current body of knowledge about the adaptations of muscle cells to exercise that are dependent on ROS

Physical Activity and Oxidative Stress in Aging.

Biological aging, characterized by changes in metabolism and physicochemical properties of cells, has an impact on public health. Environment and lifestyle, including factors like diet and physical activity, seem to play a key role in healthy aging. Several studies have shown that regular physical activity can enhance antioxidant defense mechanisms, including the activity of enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase. However, intense or prolonged exercise can also lead to an increase in reactive oxygen species (ROS) production temporarily, resulting in oxidative stress. This phenomenon is referred to as "exercise-induced oxidative stress". The relationship between physical activity and oxidative stress in aging is complex and depends on various factors such as the type, intensity, duration, and frequency of exercise, as well as individual differences in antioxidant capacity and adaptation to exercise. In this review, we analyzed what is reported by several authors regarding the role of physical activity on oxidative stress in the aging process as well as the role of hormesis and physical exercise as tools for the prevention and treatment of sarcopenia, an aging-related disease. Finally, we reported what has recently been studied in relation to the effect of physical activity and sport on aging in women.

Dose-Response Effects of Short-Term Rhodiola rosea Supplementation on Anaerobic Exercise Performance in Resistance-Trained Athletes: A Randomized, Crossover, Double-Blind, and Placebo-Controlled Study

Background: Rhodiola rosea (RR) has garnered attention for its potential ergogenic effects on athletic performance. The mechanisms underlying these effects are believed to involve improved energy metabolism and reduced exercise-induced oxidative stress. Methods: Twenty-seven resistance-trained individuals (13 males, 14 females; 22±3y; 170.4±10.7cm; 75.4±21.9kg) underwent three conditions in a randomized sequence: a low-dose RR (LD: 200mg/d of RR combined with 1.3g/d of maltodextrin), a high-dose RR (HD: 1.5g/d of RR), and a placebo (PL: 1.5g/d of maltodextrin), following an initial baseline (BL) assessment. Participants took supplements for seven days and a 7-day washout before transitioning to the subsequent conditions. Data were analyzed using a two-way (within-within) analysis of variance (p≤0.05) with LSD's post hoc when appropriate. Results: Participants' strength was evaluated using the one repetition maximum (1RM) test at BL and after each treatment phase. In the bench press, both RR doses exhibited significant enhancements compared to BL and PL, with weights being BL (69.6±39.7kg), PL (69.8±39.1kg), LD (72.2±41.1kg), and HD (73.4±41.4kg; p=0.001). Similarly, in the leg press, weights for both RR doses showed marked improvements over BL and PL, registering at BL (314.4±113.5kg), PL (326.2±117.0kg), LD (350.1±136.1kg), and HD (362.1±134.6kg; p<0.001). Muscular endurance was further probed, with participants conducting three sets at 60% of their 1RM for both exercises. In the bench press, the HD treatment showed a significant edge over BL and PL, with weights being BL (42.5±22.9kg), PL (43.2±23.0kg), LD (43.8±23.1kg), and HD (44.7±23.6kg; p=0.007). In the leg press, both RR doses outperformed BL and PL, with weights being BL (188.6±68.2kg), PL (195.1±68.6kg), LD (209.1±80.2kg), and HD (218.6±79.1kg; p<0.001). Regarding total lifting volume, both RR doses surpassed the BL measurements, with the HD regimen exceeding the PL. The volumes were BL (9792.7±4962.7kg), PL (11019.6±5389.2kg), LD (11805.1±5086.2kg), and HD (15344.8±10878.1kg; p<0.001). During the bench press evaluations, a significant uptick in mean power was observed post-RR supplementation for both dosages when compared to BL and PL, with power outputs being BL (200.7±124.4W), PL (204.1±124.4W), LD (221.6±139.6W), and HD (230.5±145.9W; p=0.007). However, metrics such as peak power, average velocity, and the outcomes of the Wingate test remained statistically unchanged (p>0.05). CONCLUSION: RR supplementation can enhance anaerobic performance in athletes, especially at higher doses. While it improved strength and endurance, some metrics, like peak power, remained unaffected. Further research is needed to understand RR's benefits fully. This study was self-funded, with the researchers covering all expenses. This approach ensures the research's independence from potential biases associated with external funding or grants. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Identification of mulberry leaf flavonoids and evaluating their protective effects on H2O2-induced oxidative damage in equine skeletal muscle satellite cells.

Introduction: Horses are susceptible to oxidative stress during strenuous endurance exercise, leading to muscle fatigue and damage. Mulberry leaf flavonoids (MLFs) possess significant antioxidant properties. However, the antioxidant efficacy of MLFs can be influenced by the extraction process, and their impact on H2O2-induced oxidative stress in equine skeletal muscle satellite cells (ESMCs) remains unexplored. Methods: Our study employed three extraction methods to obtain MLFs: ultrasound-assisted extraction (CEP), purification with AB-8 macroporous resin (RP), and n-butanol extraction (NB-EP). We assessed the protective effects of these MLFs on H2O2-induced oxidative stress in ESMCs and analyzed the MLF components using metabolomics. Results: The results revealed that pre-treatment with MLFs dose-dependently protected ESMCs against H2O2-induced oxidative stress. The most effective concentrations were 0.8mg/mL of CEP, 0.6mg/mL of RP, and 0.6mg/mL of NB-EP, significantly enhancing EMSC viability (p < 0.05). These optimized MLF concentrations promoted the GSH-Px, SOD and T-AOC activities (p < 0.05), while reducing MDA production (p < 0.05) in H2O2-induced ESMCs. Furthermore, these MLFs enhanced the gene expression, including Nrf2 and its downstream regulatory genes (TrxR1, GPX1, GPX3, SOD1, and SOD2) (p < 0.05). In terms of mitochondrial function, ESMCs pre-treated with MLFs exhibited higher basal respiration, spare respiratory capacity, maximal respiration, ATP-linked respiration compared to H2O2-induced ESMCs (p < 0.05). Additionally, MLFs enhanced cellular basal glycolysis, glycolytic reserve, and maximal glycolytic capacity (p < 0.05). Metabolomics analysis results revealed significant differences in mulberrin, kaempferol 3-O-glucoside [X-Mal], neohesperidin, dihydrokaempferol, and isobavachalcone among the three extraction processes (p < 0.05). Discussion: Our study revealed that MLFs enhance antioxidant enzyme activity, alleviate oxidative damage in ESMCs through the activation of the Nrf2 pathway, and improve mitochondrial respiration and cell energy metabolism. Additionally, we identified five potential antioxidant flavonoid compounds, suggesting their potential incorporation into the equine diet as a strategy to alleviate exercise-induced oxidative stress.

The Impact of High-Intensity Interval Exercise Including Acceleration/Deceleration Patterns on Redox Status of Healthy Male Adults

High-intensity interval exercise (HIIE) is a type of structured physical training characterized by repeated bouts of high-intensity exercise interspersed with recovery periods. Although HIIE was found to improve physical performance in a relatively short period of time, there is emerging evidence suggesting that acute HIIE may induce oxidative stress. The purpose, therefore, of the present study was to examine the effect of intermittency and/or acceleration during HIIE on oxidative stress in male participants. Nine healthy males [(age: 21.0 ± 3.0 years; height: 180.0 ± 4.0 cm; body mass: 79.4 ± 7.9 kg; maximal oxygen uptake (V˙O2max) 52.0 ± 6.0 mL·kg−1·min−1)] were recruited to perform six distinct exercise protocols of various intermittency (high, medium, and low) and acceleration (high, medium, and low) while a control session was also included. Blood samples were obtained to determine oxidative stress indices (lipid hydroperoxides, superoxide dismutase, and total glutathione) at rest, 1 h, 2 h, and 24 h following exercise on a non-motorized treadmill. The intra-individual variability of participants was observed in lipid hydroperoxides at baseline, ranging from 1.80 to 20.69 μmol·L−1. No significant differences among the six different exercise protocols in any of the oxidative stress indices evaluated were observed (p &gt; 0.05). These results suggest that the influence of various intermittency levels and acceleration patterns upon exercise-induced oxidative stress is negligible.

Trimethylamine N-Oxide Improves Exercise Performance by Reducing Oxidative Stress through Activation of the Nrf2 Signaling Pathway.

Trimethylamine N-oxide (TMAO) has attracted interest because of its association with cardiovascular disease and diabetes, and evidence for the beneficial effects of TMAO is accumulating. This study investigates the role of TMAO in improving exercise performance and elucidates the underlying molecular mechanisms. Using C2C12 cells, we established an oxidative stress model and administered TMAO treatment. Our results indicate that TMAO significantly protects myoblasts from oxidative stress-induced damage by increasing the expression of Nrf2, heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase (NQO1), and catalase (CAT). In particular, suppression of Nrf2 resulted in a loss of the protective effects of TMAO and a significant decrease in the expression levels of Nrf2, HO-1, and NQO1. In addition, we evaluated the effects of TMAO in an exhaustive swimming test in mice. TMAO treatment significantly prolonged swimming endurance, increased glutathione and taurine levels, enhanced glutathione peroxidase activity, and increased the expression of Nrf2 and its downstream antioxidant genes, including HO-1, NQO1, and CAT, in skeletal muscle. These findings underscore the potential of TMAO to counteract exercise-induced oxidative stress. This research provides new insights into the ability of TMAO to alleviate exercise-induced oxidative stress via the Nrf2 signaling pathway, providing a valuable framework for the development of sports nutrition supplements aimed at mitigating oxidative stress.

The Immunomodulatory Effects of Sulforaphane in Exercise-Induced Inflammation and Oxidative Stress: A Prospective Nutraceutical.

Sulforaphane (SFN) is a promising molecule for developing phytopharmaceuticals due to its potential antioxidative and anti-inflammatory effects. A plethora of research conducted in vivo and in vitro reported the beneficial effects of SFN intervention and the underlying cellular mechanisms. Since SFN is a newly identified nutraceutical in sports nutrition, only some human studies have been conducted to reflect the effects of SFN intervention in exercise-induced inflammation and oxidative stress. In this review, we briefly discussed the effects of SFN on exercise-induced inflammation and oxidative stress. We discussed human and animal studies that are related to exercise intervention and mentioned the underlying cellular signaling mechanisms. Since SFN could be used as a potential therapeutic agent, we mentioned briefly its synergistic attributes with other potential nutraceuticals that are associated with acute and chronic inflammatory conditions. Given its health-promoting effects, SFN could be a prospective nutraceutical at the forefront of sports nutrition.

The effects of coenzyme Q10 supplementation on biomarkers of exercise-induced muscle damage, physical performance, and oxidative stress: A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials

PurposeThis study aims to elucidate the dose-dependent effect of coenzyme Q10 supplementation (CoQ10) on exercise-induced muscle damage (EIMD), physical performance, and oxidative stress in adults. MethodsA systematic search was conducted through PubMed, Scopus, and ISI Web of Science databases up to August 2023, focusing on randomized control trials (RCTs) that investigated the effects of CoQ10 supplementation on EIMD recovery, physical performance and oxidative stress mitigation in adults. The weighted mean difference (WMD) and 95% confidence interval (95%CI) were estimated using the random-effects model. ResultsThe meta-analysis incorporated 28 RCTs, encompassing 830 subjects. CoQ10 supplementation significantly decreased creatine kinase (CK) (WMD: -50.64 IU/L; 95%CI: -74.75, -26.53, P<0.001), lactate dehydrogenase (LDH) (WMD: -52.10 IU/L; 95%CI: -74.01, -30.19, P<0.001), myoglobin (Mb) (WMD: -21.77 ng/ml; 95%CI: -32.59, -10.94, P <0.001), and Malondialdehyde (MDA) (WMD: -0.73 μmol/l; 95%CI: -1.26, -0.20, P =0.007) levels. No significant alteration in total antioxidant capacity was observed post-CoQ10 treatment. Each 100 mg/day increase in CoQ10 supplementation was correlated with a significant reduction in CK (MD: -23.07 IU/L, 95%CI: -34.27, -11.86), LDH (WMD: -27.21 IU/L, 95%CI: -28.23, -14.32), Mb (MD: -7.09 ng/ml; 95%CI: -11.35, -2.83) and MDA (WMD: -0.17 μmol/l, 95%CI: -0.29, -0.05) serum levels. Using SMD analysis, "very large" effects on LDH and "moderate" effects on CK and MDA were noted, albeit nonsignificant for other outcomes. ConclusionCoQ10 supplementation may be effective in reducing biomarkers of EIMD and oxidative stress in adults. Nevertheless, given the preponderance of studies conducted in Asia, the generalizability of these findings warrants caution. Further RCTs, particularly in non-Asian populations with large sample sizes and extended supplementation durations, are essential to substantiate these observations.

Jaboticaba berry (Myrciaria jaboticaba) supplementation protects against micro- and macrovascular dysfunction induced by eccentric exercise: a randomized clinical trial.

Physical activities that are unaccustomed and involve eccentric muscle contractions have been demonstrated to temporarily impair macrovascular and microvascular functions, which may be caused by exercise-induced oxidative stress. Jaboticaba (Myrciaria jaboticaba) is a famous Brazilian berry that has been described to exhibit high antioxidant activity. However, no human study has investigated the protective effects of jaboticaba consumption against the vascular damage induced by eccentric exercise. Therefore, the present study aimed to assess whether supplementation with jaboticaba berry juice could positively affect macro- and microvascular functions within 48 hours after eccentric exercise. This randomized, double-blind, placebo-controlled, parallel trial enrolled 24 healthy participants consuming 250 mL per day of jaboticaba berry juice (containing ∼1,300 mg of total polyphenols) or placebo for 6 days. At the baseline, pre-exercise, and 24 h and 48 h postexercise stages, blood samples were taken for analysis of reduced glutathione (GSH) levels. Also, brachial artery flow-mediated dilation (FMD), blood flow, and tissue oxygen saturation (StO2) responses to 5-minute cuff occlusion were assessed using Doppler ultrasound and near-infrared spectroscopy, respectively. Our findings revealed significant decreases in blood GSH (P < 0.001, ES = 0.76), FMD (P = 0.005, ES = 0.48), reperfusion slope of StO2 (P = 0.018, ES = 0.42) at 24 h and blood flow (P = 0.012, ES = 0.42) at 48 h following eccentric exercise in the control group as compared to the jaboticaba berry juice group. Our results demonstrated that jaboticaba berry juice prevented the exercise-induced increase in reactive oxygen species production and protected macro- and microvascular functions against the damage caused by eccentric exercise, suggesting that jaboticaba berry consumption could protect the vascular function under conditions of imbalance in redox homeostasis.

High-intensity exercise impairs intestinal barrier function by generating oxidative stress.

The intestine functions as a barrier preventing the entry of extrinsic factors into the body. This barrier function is disrupted by oxidative damage along with an impaired mucosal layer. Excessive exercise can generate oxidative stress in the intestinal tissue; however, the effect of exercise-induced oxidative stress on intestinal permeability is unclear. In this study, we examined the involvement of oxidative stress in barrier function of the ileum of mice following high-intensity exercise. Male ICR mice (12-week-old) were divided into sedentary and exercise groups. Mice in the exercise group underwent a single bout of treadmill running, and the ileum was collected for histological and biochemical analyses. Plasma fluorescence intensity level after oral administration of fluorescein isothiocyanate-dextran gradually increased until 30 min after exercise in response to intensity of exercise. Relatively high levels of oxidative proteins and low level of claudin-1, a tight-junction protein, were observed in the exercise group. Treatment with a xanthine oxidase inhibitor suppressed exercise-induced increases in intestinal permeability. Moreover, excessive exercise training for two weeks led to relatively high intestinal permeability at rest. These results suggest that high-intensity exercise increases intestinal permeability and tight junction damage, which may be mediated by oxidative stress.

How Supplementation with SOD-Rich Plant Extract, Combined with Gliadin, Can Affect Oxidative Stress Markers and Zonulin Levels in Exercise-Induced Oxidative Stress.

A randomized, double-blind, placebo-controlled study was conducted to investigate the influence of supplementation with a superoxide dismutase (SOD)-rich plant extract on markers of oxidative stress, zonulin levels and the performance of elite athletes. Participants were 30 international-level rowers, divided into an experimental group (n = 15) and a control group (n = 15). The rowers performed a maximal effort incremental test on a rowing ergometer at the beginning and at the end of the study. Markers of oxidative stress (total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), superoxide dismutase (SOD), glutathione peroxidase (GPx), advanced oxidation protein products (AOPPs), malondialdehyde (MDA), sulfhydryl (SH) groups, bilirubin, uric acid, albumin and zonulin) were determined in serum. A lower TOS (p = 0.010) and OSI (p = 0.004), a lower MDA (p = 0.001) and a higher level of SH groups (p = 0.031) were observed in the experimental group after supplementation. Physical performance was evaluated through metabolic efficiency, taking lactate levels and power output on the ergometer into account. After 6 weeks of supplementation, the relative increase in metabolic efficiency at a 4 mmol/L lactate concentration and maximal effort was significantly higher in the experimental group (p = 0.004 and p = 0.015, respectively). These results suggest that supplementation with a SOD-rich extract promotes lower oxidative stress, better antioxidant protection and, consequently, the better work performance of athletes.

Exercise-Induced Transient Oxidative Stress Is Mitigated in Down Syndrome: Insights About Redox Balance and Muscle Strength.

Reis, AL, Deus, LA, Neves, RVP, Corrêa, HL Reis, TL, Aguiar, LS Honorato, FS, Barbosa, JMS, Araújo, TB, Palmeira, TRC, Simões, HG, Prestes, J, Sousa, CV, Ide, BN, and Rosa, TdS. Exercise-induced transient oxidative stress is mitigated in Down syndrome: insights about redox balance and muscle strength. J Strength Cond Res 38(3): e125-e34, 2024-This study aimed to evaluate the acute effects of a session of resistance exercise (RE) performed with elastic tubes on the redox balance and inflammatory profile in individuals with Down syndrome (DS). Subjects ( n = 23) were allocated into 2 groups: individuals with DS (DS; n = 11) and individuals without DS (WDS; n = 12), who performed an acute RE session. Diagnostic assessment included medical history, anthropometric measures (body height, body mass, body mass index, and body composition assessment), biological collections, muscle strength assessments (handgrip and maximal voluntary isometric contraction tests), and exercises. The redox balance and inflammatory profile were assessed in urine and saliva samples before and after an acute RE session. There were no differences between WDS and DS groups for body composition ( p > 0.05). The DS group presented higher values pre and post an acute RE session with elastic tubes for oxidative and proinflammatory markers compared with WDS ( p < 0.05). Uric acid values increased from pre-acute RE session to post-acute RE session for WDS ( p < 0.0001). No differences were identified within groups for the delta analysis ( p > 0.05). Inverse correlations were found between total force and F2-isoprostane, 8OHdG, uric acid, allantoin, IL-6, TNF-α, and the TNF-α:IL-10 ratio. A positive correlation was found between IL-10 and total force. The DS group presented increased peak force in the knee extension and elbow flexion exercises (∼25 and 12%, respectively) but decreases in handgrip strength of ∼7%. The WDS group showed higher peak force values for knee extension, elbow flexion, and handgrip (∼16, 10, and 14%, respectively). The DS group had lower transient elevation of oxidative stress after an acute RE session compared with WDS. Oxidative stress and inflammation responses of DS to an acute RE session with elastic tubes may be insufficient to induce health adaptations for the same relative load compared with WDS.

Effects of Hyperthermia and Acidosis on Mitochondrial Production of Reactive Oxygen Species.

Exercise is associated with the development of oxidative stress, but the specific source and mechanism of production of pro-oxidant chemicals during exercise has not been confirmed. We used equine skeletal muscle mitochondria to test the hypothesis that hyperthermia and acidosis affect mitochondrial oxygen consumption and production of reactive oxygen species (ROS). Skeletal muscle biopsies were obtained at rest, after an acute episode of fatiguing exercise, and after a 9-week conditioning program to increase aerobic fitness. Mitochondrial oxygen consumption and ROS production were measured simultaneously using high-resolution respirometry. Both hyperthermia and acidosis increased non-phosphorylating (LEAK) respiration (5.8X and 3.0X, respectively, p<0.001) and decreased efficiency of oxidative phosphorylation. The combined effects of hyperthermia and acidosis resulted in large decreases in phosphorylating respiration, further decreasing oxidative phosphorylation efficiency from 97% to 86% (p<0.01). Increased aerobic fitness reduced the effects of acidosis on LEAK respiration. Hyperthermia increased, and acidosis decreased ROS production (2X and 0.23X, respectively, p<0.001). There was no effect of acute exercise, but an aerobic conditioning program was associated with increased ROS production during both non-phosphorylating and phosphorylating respiration. Hyperthermia increased the ratio of ROS production to O2 consumption during phosphorylating respiration, suggesting that high temperature impaired transfer of energy through the electron transfer system despite relatively low mitochondrial membrane potential. These data support the role of skeletal muscle mitochondria in the development of exercise-induced oxidative stress, particularly during forms of exercise that result in prolonged hyperthermia without acidosis.

Novel Humanized G6PD Deficient Mice Reveal Mechanisms of Increased Tolerance to Exercise As Gleaned By Multi-Omics in Models of Critical Speed

INTRODUCTION: Glucose-6-phosphate-dehydrogenase (G6PD) deficiency is the most common enzymatic deficiency in humans, affecting ~500 million people or ~6% of mankind. G6PD is the rate limiting enzyme of the pentose phosphate pathway (PPP), the main antioxidant pathway in mature red blood cells (RBCs). Activation of the PPP generates NADPH, an essential reducing equivalent for antioxidant metabolism that protects against intra- and extra-vascular hemolysis in response to oxidant stress. Impaired G6PD activity makes RBCs susceptible to hemolysis induced by oxidant challenges. Exercise-induced oxidant stress is a well-established concept in the field of physiology. Individuals with G6PD deficiency are recommended to refrain from strenuous exercise, as they are deemed to be at increased risk for hemolytic events in response to exercise-induced oxidant stress. While biochemically sound, this rationale has never been tested mechanistically, owing to ethical and technical limitations. As such, knowledge is limited regarding molecular impacts of exercise activity in G6PD deficient individuals. METHODS: Here we generated novel humanized mouse models carrying either (i) human canonical G6PD (normal activity), or two of the most common G6PD variants (ii) African (V68M - &amp;lt; 10% residual enzymatic activity) or (iii) Mediterranean (S188F - &amp;lt;1% residual enzymatic activity). We leveraged these mouse models to assess critical speed (CS), a functional measurement of the speed-to-duration relationship. To expand the molecular resolution of genetically associated adaptations to exercise, CS tests were combined with measurements of hemodynamics - including cardiac output, imaging (e.g., scanning electron microscopy of RBCs before and after exercise) and multi-omics (mass spectrometry-based metabolomics, lipidomics and proteomics) characterization of plasma, RBCs, and multiple tissue matrices including liver, heart, kidney, lung, spleen, and muscles (gastrocnemius and soleus). RESULTS: First of all, we confirmed a significant decrease in G6PD activity in RBCs from mice carrying the African and Mediterranean variants ( Figure 1). Unexpectedly, G6PD deficient mice showed ~10% faster CS compared to mice carrying the canonical human G6PD (p&amp;lt;0.0001 and p&amp;lt;0.02, Figure 1). While scanning electron microscopy showed differences before and after exercise, with accumulation of reversibly modified morphologies across all groups after the run, no significant differences were observed across groups. No significant changes in hemolysis markers were observed in plasma samples after exercise, neither at the metabolic (e.g., heme catabolites) or proteomics level (e.g., hemoglobin chains, RBC-derived proteins). Within hemodynamics, the hG6PD Med- mice are showing a higher efficiency in their cardiac function through cardiac function (p&amp;lt;0.005 - Figure 1). Pathway analysis of metabolomics data generated from RBC and plasma fractions showed significant decreases in arginine metabolism, increased glycolysis, and elevated Krebs cycle intermediates, in addition to expected differences in PPP. Specifically, in hG6PD A- RBC acylcarnitines accumulate after running. In hG6PD Med-, there are clear left ventricular differences highlighted in energy metabolism ( Figure 1). Multiomics analyses identified five major tissue clusters between heart, muscle, liver, kidney, and spleen, with G6PD function having the most significant metabolic impact on liver and soleus. RBC proteomics results highlighted deceased ferroportin (key iron transporter) in both the deficient groups, with markedly significant changes in the hG6PD Med- (p&amp;lt;0.0001). CONCLUSION: Novel humanized G6PD deficient mice maintain faster CS compared to mice. Omics approaches afford the opportunity to identify metabolic correlates to measurements of performance in relevant animal models, such as the CS model, which offer expanded mechanistic understanding of molecular bases of CS and the associated impact of G6PD deficiency. Our results not only challenge the assumption that exercise-induced oxidant stress predisposes the ~500M individuals with G6PD deficiency worldwide to increased hemolytic propensity, but rather indicate a metabolic advantage of functional polymorphisms to G6PD with respect to exercise performance, an observation that could contribute explaining the prevalence of such mutation in human populations.

Betalains Alleviate Exercise-Induced Oxidative Stress, Inflammation, and Fatigue and Improve Sports Performance: an Update on Recent Advancement.

Beetroot juice is a popular natural food supplement commonly consumed for its health and ergogenic benefits. It contains an abundance of phytochemical compounds, which have been shown to enhance sports endurance and recovery. Among them, nitrate is well-studied and known for improving performance during exercise. On the other hand, betalains, the bioactive pigment, have shown various biological activities including antioxidant, anti-inflammatory, and anti-hypertensive, which may improve exercise performance and post-exercise recovery. Additionally, free radical scavenging activities of betalains could increase nitric oxide availability in the blood, thereby improving blood flow and oxygen supply during strenuous exercise. This review article provides a critical discussion of the non-pathological conditions induced by prolonged or strenuous exercise and betalains' potential in reducing such conditions including muscle damage, inflammation, and fatigue. Additionally, the real-time application of betalains as an ergogenic compound in competitive athletes has been discussed. Finally, future directions and conclusions on the potential of betalains as a natural ergogenic aid in sport endurance are outlined. Betalains in beetroot are the major water-soluble nitrogen-containing pigment possessing high antioxidant, anti-inflammatory, and anti-fatigue activities. Betalain supplementation could alleviate exercise-induced oxidative stress, inflammation, and fatigue in competitive athletes. Betalains have the potential to become a natural ergogenic aid or nutraceutical compound for sports people during exercise and competitive performance.

Antioxidant effect of omega-3 fatty acids on exercise-induced oxidative stress in rats.

The aim of this study is to examine the effects of omega-3 supplementation on Catalase (CAT) activity, Malondialdehyde (MDA), advanced oxidation protein products (AOPP) and reduced glutathione (GSH) levels in long-term aerobic exercises in rats. 28 male Wistar albino rats (8 weeks old, 220-350 g body weight) were included in the study. The rats were given treadmill exercise for 20 minutes at an average speed of 15 cm/s, 5 days a week, for 8 weeks. The experiment was terminated at the end of the eighth week. Blood samples were taken. CAT, MDA, AOPP and GSH analyses were performed. SPSS v. 21 package program was used in the analysis of the data. The distribution of the data was examined with the normality homogeneity test, and it was determined that it was a normal distribution. As a result, the One-Way ANOVA test, one of the parametric tests, was used. Tukey test was used to determine the difference between groups. Significance levels were evaluated as (p < 0.05). Statistical analysis showed a statistically significant difference between groups in CAT, MDA and GSH levels (p < 0.05), while there were no differences between the groups in AOPP levels (p > 0.05). In the conclusion of the study, it was determined that omega-3 supplementation caused a decrease in MDA level, an increase in CAT activity and GSH level in rats exposed to chronic long-term exercise. Thus, it can be said that omega-3 supplementation in chronic long-term exercise will provide antioxidant protection against potential oxidative damage.

Effects of maslinic acid supplementation on exercise-induced inflammation and oxidative stress in water polo athletes: A randomized, double-blind, crossover, and placebo-controlled trial.

Olive fruit is rich in bioactive pentacyclic triterpenoids, primarily maslinic acid (MA). Previous studies have demonstrated that MA exhibits anti-inflammatory and anti-oxidative effects; however, it is unclear whether MA intake during training inhibits perceptual fatigue and muscle soreness in athletes. This study analyzed the effects of MA supplementation during athletic training on perceptual fatigue and muscle soreness. This randomized, double-blind, cross-over, and placebo-controlled trial involved 12 young, healthy male water polo athletes. After daily training for seven days, they ingested either olive fruit extract, containing 60 mg/day MA, or a placebo. We measured perceptual fatigue and muscle soreness during the intervention using a visual analog scale and inflammatory and oxidative stress-related proteins. Perceptual fatigue and muscle soreness and the area under the curve during the training period were significantly lower (main effect of MA; P < 0.05) following MA supplementation than those for the placebo. MA supplementation during training lowered perceptual fatigue and muscle soreness by decreasing inflammatory factors in water polo athletes. Additionally, we examined the detailed mechanism of MA, added the participant's serum to the culture medium at a 10% concentration to determine inflammation- and oxidative stress-related intracellular signals. Skeletal muscle cells (C2C12) cultured with MA-conditioned serum before and after intervention also suppressed expression of inflammation and oxidative stress-related proteins. These findings suggest that MA intake not only reduces perceptual fatigue and muscle soreness but also decreases inflammation and oxidative stress in the blood and skeletal muscle.