Antioxidant Interactions between Citrus Fruit Carotenoids and Ascorbic Acid in New Models of Animal Cell Membranes.

The regular consumption of citrus fruits by humans has been associated with lower incidence of chronic-degenerative diseases, especially those mediated by free radicals. Most of the health-promoting properties of citrus fruits derive from their antioxidant content of carotenoids and ascorbic acid (ASC). In the current work we have investigated the scavenging (against hydroxyl radical) and quenching capacities (against singlet oxygen) of four different carotenoid extracts of citrus fruits in the presence or absence of ASC (µM range) in organic solvent, aqueous solution, micelles and in an innovative biomimicking liposomal system of animal cell membrane (AML). The fruits of four varieties of citrus were selected for their distinctive carotenoid composition (liquid chromatography characterization): 'Nadorcott' mandarin and the sweet oranges 'Valencia late', 'Ruby Valencia' and 'Pinalate' mutant. The quenching activity of citrus carotenoids strongly depended on the biological assemblage: freely diffusible in organic solvent, 'Ruby Valencia' carotenoids (containing lycopene) showed the highest quenching activity, whereas 'Nadorcott' mandarin extracts, rich in ß-cryptoxanthin, prevailed in micellar systems. Interestingly, the addition of 10 µM ASC significantly increased the quenching activity of all citrus extracts in micelles: 'Valencia' orange (+53%), 'Pinalate' (+87%), 'Ruby' (4-fold higher) and 'Nadorcott' mandarins (+20%). Accurate C11-BODIPY581/591 fluorescence assays showed solid scavenging activities of all citrus extracts against AML oxidation: 'Valencia' (-61%), 'Pinalate' (-58%) and 'Ruby' oranges (-29%), and 'Nadorcott' mandarins (-70%). Indeed, all four citrus extracts tested here have balanced antioxidant properties; extracts from the 'Nadorcott' mandarin slightly prevailed overall, due, at least in part, to its high content of ß-cryptoxanthin. This study depicts some of the antioxidant interactions between citrus fruit carotenoids and ascorbic acid in models of animal cell membranes and reinforces the contribution of them in promoting health benefits for humans.

Empowering frail older adults: multicomponent elastic-band exercises and BCAA supplementation unleash physical health and preserve haematological biomarkers.

The effectiveness of Branched Chain Amino Acids (BCAAs) supplementation on enhancing exercise performance in both young and older adults remains a topic of debate. Recent research suggests that BCAAs combined with regular exercise might have an impact on human erythropoiesis, blood dynamics, and iron homeostasis. Given the increasing longevity of the global population, it is crucial to investigate the potential benefits of BCAA supplementation and regular exercise as non-pharmacological interventions for improving the overall health of frail older adults. To assess the influence of a 40-week multicomponent exercise intervention (MEP) combined BCCA supplementation on the haematological indicators of frail older adults (83-93 years old) residing in nursing homes. A prospective, naturalistic, controlled clinical trial employing an intervention-washout-intervention was conducted for this purpose. The study included four experimental groups: MEP plus BCAA supplementation (MEP + BCAA, n = 8), MEP only (n = 7), BCAA supplementation only (n = 7), and control group non exercising (CG, n = 13). Fried's physical frailty (PF) protocol was employed to stratify the participants. Additionally, the assessment included the evaluation of nutritional status, comorbidities, and anthropometric measurements. Among the several haematological markers examined, only mean cellular Haemoglobin Concentration (MCH) [F = 4.09; p < 0.03] and Mean Cell haemoglobin Concentration (MCHC) [F = 10, 323; p < 0,0001] showed significant effects of time group. Our findings demonstrate that a long-term intervention with BCAA plus MEP did not lead to significant alterations in the haematological profile. An 8-week withdrawal from interventions did not affect the frailty status in the MEP and MEP + BCAA groups, whereas the control group exhibited an increase in PF status. The findings, demonstrating the potential pro-immune effect and maintenance of MCH and MCHC levels, highlight the relevance of incorporating exercise and nutritional strategies to promote healthy aging. This study contributes to the achievement of the United Nations Sustainable Development Goals 3 (good health and well-being) and 10 (reduced Inequalities) for all.

Propentofylline Improves Thiol-Based Antioxidant Defenses and Limits Lipid Peroxidation following Gliotoxic Injury in the Rat Brainstem.

Propentofylline (PROP) is a methylated xanthine compound that diminishes the activation of microglial cells and astrocytes, which are neuronal cells strongly associated with many neurodegenerative diseases. Based on previously observed remyelination and neuroprotective effects, PROP has also been proposed to increment antioxidant defenses and to prevent oxidative damage in neural tissues. Since most neurodegenerative processes have free radicals as molecular pathological agents, the aim of this study was to evaluate the antioxidant effects of 12.5 mg·kg-1·day-1 PROP in plasma and the brainstem of Wistar rats exposed to the gliotoxic agent 0.1% ethidium bromide (EB) for 7-31 days. The bulk of the data here demonstrates that, after 7 days of EB treatment, TBARS levels were 2-fold higher in the rat CNS than in control, reaching a maximum of 2.4-fold within 15 days. After 31 days of EB treatment, lipoperoxidation in CNS was still 65% higher than that in the control. Clearly, PROP treatment limited the progression of lipoperoxidation in EB-oxidized CNS: it was, for example, 76% lower than in the EB-treated group after 15 days. Most of these effects were associated with PROP-induced activity of glutathione reductase in the brainstem: the EB + PROP group showed 59% higher GR activity than that of the EB or control groups within 7 days. In summary, aligning with previous studies from our group and with literature about MTXs, we observed that propentofylline (PROP) improved the thiol-based antioxidant defenses in the rat brainstem by the induction of the enzymatic activity of glutathione reductase (GR), which diminished lipid oxidation progression and rebalanced the redox status in the CNS.

High Doses of Caffeine Increase Muscle Strength and Calcium Release in the Plasma of Recreationally Trained Men.

The effects of acute caffeine supplementation on muscular strength remain unclear. We examined the effects of two different doses of caffeine on muscle strength and calcium in plasma compared to placebo using a crossover, randomized, double-blind, placebo-controlled design. Twenty-one (n = 21) recreationally resistance-trained participants were randomly assigned into three experimental conditions: 6 mg·kg bw−1 of caffeine (CF6); 8 mg·kg bw−1 of caffeine (CF8); or placebo (PLA), with a 7-day washout period between conditions. Muscular strength assessments were made for both upper (bench press) and lower body muscles (squat and deadlift). Calcium release in plasma was measured on five different occasions. Bench press (CF8: 100.1 ± 1.9 kg; PLA: 94.2 ± 2.5 kg), deadlift (CF8: 132.8 ± 3.5 kg; PLA: 120.7 ± 5.7 kg), and squat (CF8: 130.1 ± 4.9 kg; PLA 119.4 ± 5.4 kg) strength were all significantly (p < 0.001) improved in CF8 compared to PLA. Calcium release in plasma was significantly increased in CF8, whereas no changes were observed in CF6 or PLA. Overall, 8 mg·kg bw−1 of caffeine appears to be an effective dose to optimize upper and lower body muscular strength and calcium release in recreationally trained participants.

Updating futsal physiology, immune system, and performance.

Futsal promotes stress by handling the ball, physical contact, and exhaustive muscle contractions, elevating the risks for injury, oxidative stress, and inflammation after a training session or a match. In this review, we critically evaluate the more recent advances in the performance and health of futsal players. We searched the effects of futsal on performance, physiological parameters, muscle injury, inflammation, and oxidative stress. Although the stressful factors apply to all futsal players, goalkeepers require special attention during the competition and the recovery phase. We also show that the FIFA injury prevention programme, called The 11+, is effective in improving athletic performance and avoiding injury in futsal players. Research with different training durations and intensities and a wider range of studies involving oxidative stress, inflammation, and physiological mechanisms are of interest to design a more precise map of the biochemical regulation of training load and competition season in futsal.

Effect of a 40-weeks multicomponent exercise program and branched chain amino acids supplementation on functional fitness and mental health in frail older persons.

BACKGROUND: The ageing process implies several physiological and psychological changes that hence affect the general health, mood states, and quality of life of older persons. Exercise and adequate nutrition are renowned non-pharmacological strategies that significantly delay and alleviate the adverse consequences of the ageing process. This study aimed to evaluate the effects of branched-chain amino acid (BCAA) supplementation and a multicomponent exercise program (ME) on the physical frailty and mood states of older persons. METHODS: 35 participants (women and men; 83 ± 3 years old) from residential care homes were submitted to a 40-week exercise-washout-retraining intervention (16 weeks of the elastic band based exercise and/or supplementation, 8 weeks of washout, and 16 weeks of multicomponent exercise and/or resupplementing), with or without BCAA supplementation. The experimental groups were: (i) ME plus BCAA supplementation (ME+BCAA); (ii) ME; (iii) BCAA supplementation (BCAA), and (iv) control group (CG). Fried's phenotype was used to assess frailty prevalence. Geriatric Depression Scale (GDS), Profile of Mood State (POMS), Mini-Mental State Examination (MMSE), were used to access mental health and cognition. The Short Physical Performance Battery (SPPB) was used to access functional capacity. Salivary testosterone levels (ST) were also determined to access the anabolic effects of the intervention. RESULTS: Exercise was effective in improving functional capacity and prevented the increase in frailty that occurred in the non-exercising CG, where the frailty scores increased over time (p < 0.01). BCAAs supplement alone had no impact on functional fitness, but in a short time (16 weeks) contributed to diminishing frailty and combined with exercise may have the potential to reduce the effect of a detraining period on functional capacity. Salivary testosterone levels correlated with handgrip strength and could be a useful indicator of susceptibility to frailty. No effects were found for mood states, cognition, and depression. CONCLUSION: This study showed that a long-term exercise program, independent of being multicomponent or strength elastic band-based, was effective in improving functional capacity and prevented an increase in frailty in frail and pre-frail older persons living in residential care homes.

l-Glutamine supplementation enhances glutathione peroxidase and paraoxonase-1 activities in HDL of exercising older individuals.

BACKGROUND: Oxidative stress is an important factor in the formation of atherosclerotic plaques. High-density lipoprotein (HDL) harbors paraoxonase-1 (PON-1) and glutathione peroxidase (GPx), key enzymes in the protection against the harmful effects of oxidative stress. Although exercise training can increase both HDL-c content and its antioxidant action, and glutamine (Gln) intake also promotes GPx-based defenses, the association between exercise training and Gln in the regulation of PON-1 activity was not explored. Therefore, the objective of this study was to investigate the effects of Gln supplementation on the redox balance and on the total HDL antioxidant capacity by evaluation of the activity of PON-1 and GPx enzymes in physically exercised elderly individuals compared to non-exercised ones. METHODS: Fifty-one practitioners of a combined exercise training program (CET, age: 71.9 ± 5.7 years) and 32 non-practitioners (NP, age: 73 ± 6.3 years) participated in the study. CET and NP groups were separated into 2 subgroups according to the supplementation: Gln, 0.3 g/kg/day + 10 g maltodextrin (CET-Gln, n = 26; and NP-Gln, n = 16) or placebo, 10 g maltodextrin (CET-PL, n = 25; and NP-PL, n = 16). Blood samples were drawn at baseline and after 30 days after commencement of the supplementation for biochemical and enzyme activity analyses. RESULTS: Increased HDL-c, total peroxidase (PRx), and GPx activities were found in both CET-Gln and NP-Gln after the supplementation period, compared to baseline, in opposition to CET-PL and NP-PL groups. PON-1 activity increased only in CET-Gln. In both CET-Gln and NP-Gln groups, there was a reduction of the total peroxides/PRx, iron/PRx, and total peroxides/GPX ratios after supplementation. In CET-Gln, thiobarbituric acid-reactive substances (TBARS)/PRx and TBARS/GPx ratios were also lower after supplementation. CET-Gln and CET-PL subgroups had lower glycemia than NP-Gln and NP-PL, either at baseline or after the supplementation periods. The other parameters were unchanged after supplementation [total cholesterol, LDL-c, triglycerides, non-HDL cholesterol, total peroxides, TBARS, iron serum, Trolox-equivalent antioxidant capacity (TEAC), and uric acid]. CONCLUSIONS: Gln supplementation can increase glutathione peroxidase activity regardless the individuals were physically active or sedentary, but the PON-1 activity only increased in physically active individuals. These results show the potential of Gln supplementation in the maintenance of the vascular redox balance, with potential implications for atherogenesis protection.

L-Glutamine Supplementation Enhances Strength and Power of Knee Muscles and Improves Glycemia Control and Plasma Redox Balance in Exercising Elderly Women.

We investigated the effects of oral L-glutamine (Gln) supplementation, associated or not with physical exercises, in control of glycemia, oxidative stress, and strength/power of knee muscles in elderly women. Physically active (n = 21) and sedentary (n = 23) elderly women aged 60 to 80 years were enrolled in the study. Plasma levels of D-fructosamine, insulin, reduced (GSH) and oxidized (GSSG) glutathione, iron, uric acid, and thiobarbituric acid-reactive substances (TBARs) (lipoperoxidation product), as well as knee extensor/flexor muscle torque peak and average power (isokinetic test), were assessed pre- and post-supplementation with Gln or placebo (30 days). Higher plasma D-fructosamine, insulin, and iron levels, and lower strength/power of knee muscles were found pre-supplementation in the NPE group than in the PE group. Post-supplementation, Gln subgroups showed higher levels of GSH, GSSG, and torque peak, besides lower D-fructosamine than pre-supplementation values. Higher muscle average power and plasma uric acid levels were reported in the PE + Gln group, whereas lower insulin levels were found in the NPE + Gln than pre-supplementation values. TBARs levels were diminished post-supplementation in all groups. Gln supplementation, mainly when associated with physical exercises, improves strength and power of knee muscles and glycemia control, besides boosting plasma antioxidant capacity of elderly women.

Effect of Training-Detraining Phases of Multicomponent Exercises and BCAA Supplementation on Inflammatory Markers and Albumin Levels in Frail Older Persons.

Nowadays, it is accepted that the regular practice of exercise and branched-chain amino acids supplementation (BCAAs) can benefit the immune responses in older persons, prevent the occurrence of physical frailty (PF), cognitive decline, and aging-related comorbidities. However, the impact of their combination (as non-pharmacological interventions) in albumin and the inflammatory markers is not fully understood. Therefore, we investigated the effect of a 40-week multifactorial intervention [MIP, multicomponent exercise (ME) associated or not with BCAAs] on plasma levels of inflammatory markers and albumin in frail older persons (≥75 years old) living at residential care homes (RCH). This study consisted of a prospective, naturalistic, controlled clinical trial with four arms of multifactorial and experimental (interventions-wahshout-interventions) design. The intervention groups were ME + BCAAs (n = 8), ME (n = 7), BCAAs (n = 7), and control group (n = 13). Lower limb muscle-strength, cognitive profile, and PF tests were concomitantly evaluated with plasma levels of albumin, anti- and pro-inflammatory cytokines [Interleukin-10 (IL-10) and Tumor Necrosis Factor-alpha (TNF-α) respectively], TNF-α/IL-10 ratio, and myeloperoxidase (MPO) activity at four different time-points: Baseline (T1), after 16 weeks of multifactorial intervention (T2), then after a subsequent 8 weeks washout period (T3) and finally, after an additional 16 weeks of multifactorial intervention (T4). Improvement of cognitive profile and muscle strength-related albumin levels, as well as reduction in the TNF-α levels were found particularly in ME plus BCAAs group. No significant variations were observed over time for TNF-α/IL-10 ratio or MPO activity. Overall, the study showed that MIP triggered slight alterations in the inflammatory and physical function of the frail older participants, which could provide independence and higher quality of life for this population.

L-Glutamine Supplementation Improves the Benefits of Combined-Exercise Training on Oral Redox Balance and Inflammatory Status in Elderly Individuals.

Although regular combined aerobic-resistance exercises can ameliorate the inflammatory status and redox balance in elderly population, it is unclear whether protein or specific amino acid supplementation could improve such benefits. Therefore, we aimed to evaluate the inflammatory status and redox indexes through of the saliva of 34 elderly subject nonpractitioners (NP group, 73.3 ± 6.6 years) and 49 elderly subject practitioners of a combined-exercise training in moderate intensity (CET group, 71.9 ± 5.8 years) before (pre) and after (post) 30 days of supplementation with L-glutamine (Gln) or placebo (PL). Our results showed that, both in pre- and postsupplementation, the salivary levels of nitric oxide (NO·) and TNF-α were lower, whereas the levels of uric acid and IL-10 (as well as IL-10/TNF-α ratio) were higher in the CET groups than in the NP groups. In postsupplementation, both groups supplemented with Gln (NP-Gln and CET-Gln) showed higher salivary uric acid levels compared to baseline. In addition, lower NO· levels were found in the CET-Gln group postsupplementation than presupplementation values. Whereas the CET-Gln group showed lower GSH levels postsupplementation, NP-Gln subjects showed lower GSSG levels at the same time point, both compared to baseline. Interestingly, salivary peroxidase activity was lower only in NP groups (NP-PL and NP-Gln) postsupplementation than baseline values. A positive significant correlation between salivary peroxidase activity and GSH levels, and also between salivary peroxidase activity and uric acid levels were observed in the CET-Gln group both pre- and postsupplementation. No differences were found in albumin, total antioxidant activity (TEAC), and reducing power analysis between groups, pre- or postsupplementation. In conclusion, the elderly subjects from the CET group showed a better inflammatory response and redox balance and, for the first time, it was shown that daily supplementation with Gln for 30 days can improve these benefits with putative association with a healthy aging.

Oxidative stress and toxicology of Cu2+ based on surface areas in mixed cultures of green alga and cyanobacteria: The pivotal role of H2O2.

The toxicity of heavy metals in algal monocultures is well studied and is mediated by reactive oxygen and nitrogen species (ROS/RNS). However, little is known about the toxicity of heavy metals and the mechanisms involved in mixed cultures. Here we examine the oxidative stress and toxic effects of Cu2+ on the green alga Dunaliella salina (DS) and the cyanobacteria Synecochoccus elongatus (SE) in both mono- and mixed cultures. We find that both species benefit in mixed cultures and acquire higher resistance to Cu2+ toxicity, with a particularly marked effect on SE. DS has a larger surface area than SE, so increases in the number of DS cells compared to SE diminishes the proportion of SE surface area exposed to Cu2+, and contributes to increasing cyanobacterial resistance in mixed cultures. However, these mixed cultures also display as an unexpected property an increased resistance of DS in mixed cultures. SE and DS cells showed significant differences on the kinetics of H2O2 production and antioxidant capacities. The integrated (overall) redox response of mixed cultures, in terms of total amount of H2O2 produced, was proportional to the total surface area of algal species exposed to Cu2+, independent of algal composition in mixed systems. However, mixed cultures display emergent properties, as the time course of H2O2 accumulation is not a simple function of the composition of the mixed cultures. Emergent properties are also observed in the speed of membrane lipid oxidation by the two species, as measured using mixed cultures in which only one of the two species is labeled using the membrane oxidation indicator C11-BODIPY581/591. We suggest that, in addition to H2O2¸ other redox signals (e.g. NO) and allelochemicals (auxins, cytokinins, etc.) may be used to construct a complex inter-species communication network. This could allow mixed algal systems, whatever their composition, to integrate their cellular responses and perform as a coherent unit against toxic Cu2+ ions.

Combined Exercise Training Performed by Elderly Women Reduces Redox Indexes and Proinflammatory Cytokines Related to Atherogenesis.

Cardiovascular benefits for the general population of combined aerobic-resistance exercise training are well-known, but the impact of this exercise training modality on the plasma lipid, inflammatory, and antioxidant status in elderly women that are exposed to a great risk of developing ischemic cardio- and cerebrovascular diseases has not been well investigated. So, we aimed to evaluate the plasma lipids, oxidative stress, and inflammatory cytokines in 27 elderly women (TRAINED group, 69.1 ± 8.1 yrs) that were performing moderate intensity combined aerobic-resistance exercise training (3 times/week for at least 18 months) and in 27 sedentary elderly women (SED group, 72.0 ± 6.4 yrs), not submitted to exercise training for at least 5 yrs. Our results showed that BMI was lower in the TRAINED group than in the SED group (25.1 ± 3.2 vs. 28.7 ± 5.1, p < 0.05). The TRAINED group had lower glycemia (92 ± 3 vs. 118 ± 12, p < 0.05), glycated hemoglobin (5.9 ± 0.1 vs. 6.4 ± 0.2, p < 0.05), and triglycerides (98 (75-122) vs. 139 (109-214), p < 0.01); equal total cholesterol (199 (175-230) vs. 194 (165-220)), LDL-cholesterol (108 (83-133) vs. 109 (98-136)), and non-HDL-cholesterol (54 (30-74) vs. 62 (26-80)); and also higher HDL-cholesterol (64 (52-77) vs. 52 (44-63), p < 0.01) and LDL-C/oxLDL ratio (13378 ± 2570 vs. 11639 ± 3113, p < 0.05) compared to the SED group. Proinflammatory cytokines as IL-1ß (11.31 ± 2.4 vs. 28.01 ± 4.7, p < 0.05), IL-6 (26.25 ± 7.4 vs. 49.41 ± 17.8, p < 0.05), and TNF-α (25.72 ± 2.8 vs. 51.73 ± 4.2, p < 0.05) were lower in the TRAINED group than in the SED group. The TRAINED group had lower total peroxides (26.3 ± 7.4 vs. 49.0 ± 17.8, p < 0.05) and oxidized LDL (1551 ± 50.33 vs. 1773 ± 74, p < 0.02) and higher total antioxidant capacity (26.25 ± 7.4 vs. 49.41 ± 17.8, p < 0.001) compared to the SED group. In conclusion, in TRAINED women, BMI was lower, plasma lipid profile was better, plasma oxidative stress was diminished, and there was less expression of proinflammatory interleukins than in SED, suggesting that combined aerobic-resistance exercise training may promote the protection against the complications of ischemic cardio- and cerebrovascular disease in elderly women.

High doses of sodium bicarbonate increase lactate levels and delay exhaustion in a cycling performance test.

OBJECTIVES: It is well established that ingestion of sodium bicarbonate (NaHCO3) causes metabolic alkalosis. However, there is no consensus in terms of optimal NaHCO3 doses leading to enhanced performance. This study aimed to determine the effects of different NaHCO3 doses on performance and lactate clearance in non-professional cyclists. METHODS: Twenty-one cyclists performed the following three double-blind trials: 1) ingestion of 0.3 g · kg-1 body weight (BW) of placebo; 2) ingestion of 0.1 g · kg-1 BW NaHCO3 plus 0.2 g · kg-1 BW placebo (0.1 BC); and 3) ingestion of 0.3 g · kg-1 BW NaHCO3 (0.3 BC). Performance was evaluated after warm-up on the bike followed by a performance test until exhaustion. Lactate levels were monitored in blood samples before and immediately after performance tests. RESULTS: Lactate levels in the blood were significantly higher after exercise in 0.3 BC and 0.1 BC (15.12 ± 0.92 versus 10.3 ± 1.22 and 13.24 ± 0.87 versus 10.3 ± 1.22 mmol/L; P < 0.05) compared with control. Significant improvements in performance were only identified in 0.3 BC group (76.42 ± 2.14; P = 0.01). CONCLUSIONS: The present study found that 0.3 g · kg-1 BW NaHCO3 is effective in improving performance and improving blood lactate levels in cyclists compared with control and 0.1 g · kg-1 BW NaHCO3.

Dietary Carotenoid Roles in Redox Homeostasis and Human Health.

Classic nutrition believed that healthy diets should simply provide sufficient antioxidant loads to organisms, to hamper free radical processes and avoid oxidative stress. Current redox biology was proven much more intricate. Carotenoids are bioactive compounds in the human diet with a multifaceted role in redox metabolism. This perspective discusses the participation of α/ß-carotene, lutein, zeaxanthin, lycopene, ß-cryptoxanthin, astaxanthin, and derivatives in redox homeostasis focusing on (i) their antioxidant/pro-oxidant activities, (ii) control of gene expression via Nrf2-Keap1 and NF-κB pathways, and (iii) their link with (sub)cellular redox circuits, as part of the "redox code" that orchestrates physiological processes and health in humans.

Astaxanthin Restrains Nitrative-Oxidative Peroxidation in Mitochondrial-Mimetic Liposomes: A Pre-Apoptosis Model.

Astaxanthin (ASTA) is a ketocarotenoid found in many marine organisms and that affords many benefits to human health. ASTA is particularly effective against radical-mediated lipid peroxidation, and recent findings hypothesize a "mitochondrial-targeted" action of ASTA in cells. Therefore, we examined the protective effects of ASTA against lipid peroxidation in zwitterionic phosphatidylcholine liposomes (PCLs) and anionic phosphatidylcholine: phosphatidylglycerol liposomes (PCPGLs), at different pHs (6.2 to 8.0), which were challenged by oxidizing/nitrating conditions that mimic the regular and preapoptotic redox environment of active mitochondria. Pre-apoptotic conditions were created by oxidized/nitr(osyl)ated cytochrome c and resulted in the highest levels of lipoperoxidation in both PCL and PCPGLs (pH 7.4). ASTA was less protective at acidic conditions, especially in anionic PCPGLs. Our data demonstrated the ability of ASTA to hamper oxidative and nitrative events that lead to cytochrome c-peroxidase apoptosis and lipid peroxidation, although its efficiency changes with pH and lipid composition of membranes.

Effect of exercise-induced dehydration on circulatory markers of oxidative damage and antioxidant capacity.

Dehydration is a common event associated with exercise. However, few studies have examined the effects of dehydration on plasma redox status in humans. Eighty-two athletes were recruited and baseline anthropometrics and blood samples were obtained. Athletes then engaged in a dehydration protocol, training until 3% of preweight body mass was lost. Athletes returned to the lab and had postdehydration blood collected. Athletes then consumed an isotonic drink until pre-exercise body weight was reestablished. Blood was then recollected (1 h post full rehydration (PFR)). Samples were centrifuged and the plasma snap frozen in liquid nitrogen and stored at -80 °C. Lipid and protein oxidative stress was determined by measuring F2-isoprostanes and protein carbonyls (PC), respectively. Antioxidant capacity was determined by the ferric reducing ability of plasma (FRAP) and trolox equivalent antioxidant capacity (TEAC) assays. Plasma osmolality was determined using an osmometer. Statistical analysis utilized a 1-way ANOVA with posthoc testing. Values are reported as mean ± SD. Plasma osmolality was significantly elevated immediately postdehydration (p ≤ 0.001) but decreased to baseline at PFR. Plasma TEAC increased immediately postdehydration and at PFR (p ≤ 0.001). FRAP increased immediately postdehydration (p ≤ 0.001) and decreased to below baseline at PFR (p ≤ 0.05). Conversely, F2-isoprostanes declined significantly from baseline to immediately postdehydration and then significantly rose at PFR (p ≤ 0.001), whereas PC declined at PFR (p ≤ 0.01). This study indicates that dehydration and exercise cause a significant increase in plasma osmolality and antioxidant potential immediately postexercise. We propose dehydration significantly elevates antioxidant concentration which suppresses F2-isoprostanes and PC.

Effect of 1 Repetition Maximum, 80% Repetition Maximum, and 50% Repetition Maximum Strength Exercise in Trained Individuals on Variations in Plasma Redox Biomarkers.

Polotow, TG, Souza-Junior, TP, Sampaio, RC, Okuyama, AR, Ganini, D, Vardaris, CV, Alves, RC, McAnulty, SR, and Barros, MP. Effect of 1RM, 80%RM, and 50%RM strength exercise in trained individuals on variations in plasma redox biomarkers. J Strength Cond Res 31(9): 2489-2497, 2017-For decades, scientists have examined the participation of oxygen/nitrogen species in anaerobic-like exercises, especially weightlifting and resistance exercises. The balance between the production of oxyradicals and antioxidant responses during anaerobic-like exercises is essential to assure adaptation to the physiological benefits of strength training and to prevent chronic harmful effects. The aim of this study is to examine the hypothesis that different weight loads (1 repetition maximum (RM), 80%RM, and 50%RM) lifted until exhaustion could impose distinct oxidative insults and elicit diverse antioxidant responses in plasma of young trained subjects. Glucose (+10%), lactate (+65%), urea (+30%), free iron (+65%), reduced/oxidized glutathione (+14 and +23%, respectively), and xanthine oxidase activity (2.2-fold) significantly increased after the 1RM test, whereas plasma antioxidant capacity dropped by 37%. When lower weight loads were applied (80%RM and 50%RM tests), heme-iron (+15 and +20%, respectively) became the prevalent pro-oxidant, although glutathione responses were only detected after 80%RM (+14%). Lactate concentration in plasma continuously increased, by 2.9-fold (80%RM) and 3.6-fold higher (50%RM test). We demonstrated that 1RM tests significantly diminish the antioxidant capacity of plasma because of iron overload, whereas 80%RM tests require higher involvement of glutathione molecules to counteract heme-iron oxidative insult. Mild redox imbalances promoted by heme-iron were found in plasma after 50%RM. Although we did not observe overall changes in muscle damage in young trained subjects, we cannot exclude the need for specific antioxidant supplementation depending on the strength protocols applied, especially for less responsive groups, such as sedentary and elderly populations.

Redox Status and Neuro Inflammation Indexes in Cerebellum and Motor Cortex of Wistar Rats Supplemented with Natural Sources of Omega-3 Fatty Acids and Astaxanthin: Fish Oil, Krill Oil, and Algal Biomass.

Health authorities worldwide have consistently recommended the regular consumption of marine fishes and seafood to preserve memory, sustain cognitive functions, and prevent neurodegenerative processes in humans. Shrimp, crabs, lobster, and salmon are of particular interest in the human diet due to their substantial provision of omega-3 fatty acids (n-3/PUFAs) and the antioxidant carotenoid astaxanthin (ASTA). However, the optimal ratio between these nutraceuticals in natural sources is apparently the key factor for maximum protection against most neuro-motor disorders. Therefore, we aimed here to investigate the effects of a long-term supplementation with (n-3)/PUFAs-rich fish oil, ASTA-rich algal biomass, the combination of them, or krill oil (a natural combination of both nutrients) on baseline redox balance and neuro-inflammation indexes in cerebellum and motor cortex of Wistar rats. Significant changes in redox metabolism were only observed upon ASTA supplementation, which reinforce its antioxidant properties with a putative mitochondrial-centered action in rat brain. Krill oil imposed mild astrocyte activation in motor cortex of Wistar rats, although no redox or inflammatory index was concomitantly altered. In summary, there is no experimental evidence that krill oil, fish oil, oralgal biomass (minor variation), drastically change the baseline oxidative conditions or the neuro-inflammatory scenario in neuromotor-associated rat brain regions.

Effects of N-acetylcysteine on skeletal muscle structure and function in a mouse model of peripheral arterial insufficiency.

OBJECTIVE: Abnormalities in skeletal muscle structure and function are important contributors to exercise intolerance and functional decline in peripheral arterial disease. In this study, we tested the hypothesis that administration of N-acetylcysteine (NAC) would improve fatigue resistance and ameliorate the histopathological changes in skeletal muscle in a mouse model of peripheral arterial disease. We also anticipated that NAC treatment would lower the levels of biomarkers of oxidative damage in the ischemic muscle. METHODS: Male Balb/c mice were subjected to bilateral ligation of the femoral artery and, after 2 weeks of recovery, received daily intraperitoneal injections of either NAC (150 mg/kg) or saline for 15 days. At the end of the treatment, the extensor digitorium longus (EDL) and soleus muscles were excised for assessment of contractile function in vitro and histological analysis. Free malondialdehyde and protein carbonyl levels were measured in the gastrocnemius muscle. RESULTS: In the soleus muscle, force after 10 minutes of submaximal tetanic stimulation (60 Hz, 300 ms trains, 0.3 trains/s) was higher (P < .05) in NAC-treated animals (45% ± 3% of the initial value; n = 7) when compared with controls (30.3% ± 3%; n = 8). No differences were found in fatigue development between groups in the EDL muscle (ligated NAC, 35.7% ± 1.9%; ligated saline, 37.5% ± 1.1%). In addition, there was a tendency for lower levels of connective tissue deposition in the soleus of animals treated with NAC (n = 6) when compared with those that received only saline (n = 9) (ligated NAC, 16% ± 2% vs ligated saline, 24% ± 2%; P = .057). No differences were found in lipid peroxidation or protein carbonyl levels between ligated saline and ligated NAC groups. CONCLUSIONS: Taken together, these results indicate that treatment with NAC improves fatigue resistance in the soleus but not the EDL muscle in a model of peripheral arterial insufficiency. CLINICAL RELEVANCE: Despite the increasing burden of peripheral arterial disease (PAD) and its detrimental consequences on the quality of life of the patients, few pharmacological therapies have shown to evoke meaningful effects on functional performance in these individuals. N-acetylcysteine is approved for clinical use, has minimal side effects and most important, has shown to consistently improve exercise performance in animals and humans. In this study, we showed, for the first time, that treatment with this drug at a dose amenable for clinical application evoked marked effects on fatigue resistance in the soleus muscle in a mouse model of PAD. These encouraging findings set the stage for translational studies to determine the acute and long-term impact of this drug on walking capacity in patients with PAD.

Astaxanthin supplementation delays physical exhaustion and prevents redox imbalances in plasma and soleus muscles of Wistar rats.

Astaxanthin (ASTA) is a pinkish-orange carotenoid commonly found in marine organisms, especially salmon. ASTA is a powerful antioxidant and suggested to provide benefits for human health, including the inhibition of LDL oxidation, UV-photoprotection, and prophylaxis of bacterial stomach ulcers. Exercise is associated to overproduction of free radicals in muscles and plasma, with pivotal participation of iron ions and glutathione (GSH). Thus, ASTA was studied here as an auxiliary supplement to improve antioxidant defenses in soleus muscles and plasma against oxidative damage induced by exhaustive exercise. Long-term 1 mg ASTA/kg body weight (BW) supplementation in Wistar rats (for 45 days) significantly delayed time to exhaustion by 29% in a swimming test. ASTA supplementation increased scavenging/iron-chelating capacities (TEAC/FRAP) and limited exercise-induced iron overload and its related pro-oxidant effects in plasma of exercising animals. On the other hand, ASTA induced significant mitochondrial Mn-dependent superoxide dismutase and cytosolic glutathione peroxidase antioxidant responses in soleus muscles that, in turn, increased GSH content during exercise, limited oxidative stress, and delayed exhaustion. We also provided significant discussion about a putative "mitochondrial-targeted" action of ASTA based on previous publications and on the positive results found in the highly mitochondrial populated (oxidative-type) soleus muscles here.