Liver L-glutamine is an important vehicle for the transport of ammonia and intermediary metabolism of amino acids between tissues, particularly under catabolic situations, such as high-intensity exercise. Hence, the aim of this study was to investigate the effects of oral supplementations with L-glutamine in its free or dipeptide forms (with L-alanine) on liver glutamine-glutathione (GSH) axis, and 70 kDa heat shock proteins (HSP70)/heat shock transcription factor 1 (HSF1) expressions. Adult male Wistar rats were 8-week trained (60 min/day, 5 days/week) on a treadmill. During the last 21 days, the animals were daily supplemented with 1 g of L-glutamine/kg body weight per day in either l-alanyl-L-glutamine dipeptide (DIP) form or a solution containing L-glutamine and l-alanine in their free forms (GLN+ALA) or water (controls). Exercise training increased cytosolic and nuclear HSF1 and HSP70 expression, as compared with sedentary animals. However, both DIP and GLN+ALA supplements enhanced HSF1 expression (in both cytosolic and nuclear fractions) in relation to exercised controls. Interestingly, HSF1 rises were not followed by enhanced HSP70 expression. DIP and GLN+ALA supplements increased plasma glutamine concentrations (by 62% and 59%, respectively) and glutamine to glutamate plasma ratio in relation to trained controls. This was in parallel with a decrease in plasma ammonium levels. Supplementations increased liver GSH (by 90%), attenuating the glutathione disulfide (GSSG) to GSH ratio, suggesting a redox state protection. In conclusion, oral administration with DIP and GLN+ALA supplements in endurance-trained rats improve liver glutamine-GSH axis and modulate HSF1 pathway.
Éder Ricardo Petry, Vinicius Fernandes Cruzat, Thiago Gomes Heck, Paulo Ivo Homem de Bittencourt Jr., and Julio Tirapegui
Matthew J. McAllister, Joni A. Mettler, Kyle Patek, Matthew Butawan, and Richard J. Bloomer
; Kidd, 2011 ). ASTA also acts as an indirect antioxidant, enhancing endogenous glutathione (GSH) concentrations in rats ( Andriani et al., 2019 ). Dietary ASTA supplementation has been shown to produce improvements to numerous aspects of cardiometabolic and overall health through its antioxidative
Allan H. Goldfarb, Stephen W. Patrick, Scott Bryer, and Tongjian You
Vitamin C supplementation (VC) (either 500 or 1000 mg/d for 2 wk) was compared to a placebo treatment (P) to ascertain if VC could influence oxidative stress. Twelve healthy males (25 ± 1.4 y) were randomly assigned in a counter-balanced design with a 2-wk period between treatments. Data were analyzed using repeated measures ANOVA. Exercise intensity measures (VO2, RER, RPE, HR, lactate) were similar across treatments. Resting blood oxidative-stress markers were unaffected by treatment. Exercise decreased total blood glutathione (TGSH) and reduced glutathione (GSH) and increased oxidized glutathione (GSSG) (P < 0.01) independent of treatment. Protein carbonyls (PC) increased 3.8 fold in the P (P < 0.01). VC attenuated the PC exercise response in a dose-dependent manner (P < 0.01). Thiobarbituric acid reactive substances (TBARS) was not influenced by exercise (P = 0.68) or VC. These data suggest that VC supplementation can attenuate exercise-induced protein oxidation in a dose-dependent manner with no effect on lipid peroxidation and glutathione status.
S.C. Bryer and A.H. Goldfarb
This study investigated if vitamin C supplementation before and after eccentric exercise could reduce muscle soreness (MS), oxidative stress, and muscle function. Eighteen healthy men randomly assigned to either a placebo (P) or vitamin C (VC) (3 g/d) treatment group took pills for 2 wk prior and 4 d after performing 70 eccentric elbow extensions with their non-dominant arm. MS increased in both groups with significantly reduced MS for the first 24 h with VC. Range of motion was reduced equally in both groups after the exercise (P ≥ 0.05). Muscle force declined equally and was unaffected by treatment. VC attenuated the creatine kinase (CK) increase at 48 h after exercise with similar CK after this time. Gluta-thione ratio (oxidized glutathione/total glutathione) was significantly increased at 4 and 24 h with P but VC prevented this change. These data suggest that vitamin C pretreatment can reduce MS, delay CK increase, and prevent blood glutathione oxidation with little influence on muscle function loss.
Leonardo F. Ferreira, Kenneth S. Campbell, and Michael B. Reid
N-acetylcysteine (NAC) is a thiol donor with antioxidant properties that has potential use as an ergogenic aid. However, NAC is associated with adverse reactions that limit its use in humans.
The authors evaluated NAC efficacy as a thiol donor before handgrip exercise, measuring changes in serum cysteine and glutathione status and recording adverse reactions in adult subjects across a range of doses.
Healthy individuals ingested NAC capsules (9 ± 2 or 18 ± 4 mg/kg) or solution (0, 35, 70, or 140 mg/kg). Venous blood samples were collected and subjects answered a questionnaire about adverse reactions.
Low doses of NAC (capsules) did not affect plasma cysteine or glutathione or cause adverse reactions. Adverse reactions to NAC solution were predominantly mild and gastrointestinal (GI). Intensity of GI reactions to 140 mg/kg NAC was significantly higher than placebo (in a.u., 0.67 ± 0.16 vs. 0.07 ± 0.04; p < .05). Plasma cysteine concentration increased with NAC dose from 9.3 ± 0.7 μM (placebo) to 65.3 ± 6.7 μM (140 mg/kg); however, there was no difference (p > .05) in plasma cysteine for 70 mg/kg vs. 140 mg/kg. Similar increases were observed for the ratio of cysteine to total cysteine, which was directly related to handgrip exercise performance. Plasma glutathione was elevated and oxidized glutathione diminished (p < .05) with NAC 140 mg/kg vs. placebo.
NAC effects on plasma thiols are maximized by oral administration of 70 mg/kg, a dose that does not cause significant adverse reactions.
Maximiliano I. Schaun, Leonardo Lisboa Motta, Rayane Teixeira, Fábio Klamt, Juliane Rossato, Alexandre Machado Lehnen, Maria Cláudia Irigoyen, and Melissa M. Markoski
In acute myocardial infarction (AMI), reactive oxygen species may cause irreversible damage to the heart tissue. Physical training is capable of enhancing antioxidant capacity, acting as a cardioprotective factor. We assessed the preventive effects of physical training on the antioxidant and functional responses of the heart of Wistar Kyoto rats after AMI. Wistar Kyoto rats (n = 12) were allocated to sedentary (SED) or trained (EXE—aerobic training on a treadmill) groups. Echocardiographic exams were performed 48 hr before and 48 hr after the induction of AMI. Superoxide dismutase (SOD) and catalase (CAT) activities, and total glutathione (GSH) were measured in vitro in the heart tissue. After AMI, the EXE group showed higher left ventricular shortening fraction (29%; p = .004), higher cardiac output (37%; p = .032) and reduced myocardial infarction size (16%; p = .007) than SED. The EXE group showed a higher nonenzymatic antioxidant capacity (GSH, 23%; p = .004), but the SOD and CAT activities were higher in SED (23% SOD; p = .021 and 20% CAT; p = .016). In addition, the SOD activity was positively correlated with myocardial infarction size and inversely correlated with cardiac output. Physical training partially preserved cardiac function and increased intracellular antioxidant response in cardiac tissue of animals after AMI.
Allan H. Goldfarb, Richard J. Bloomer, and Michael J. McKenzie
To examine the effects of an antioxidant treatment on blood lactate, protein carbonyls (PC), and glutathione status, 42 male rats were assigned to either a control treatment (water, C) or one of two Microhydrin® treatments (added to water, MH I or MH II). Rats from each treatment were assigned to either exercise (60 min of running) or rest. A treatment-by-time interaction was noted for blood lactate, with elevations only in the C and MH I treatments post-exercise (~ 2.54 and 2.5 mM, respectively). Both treatment and time main effects were noted for PC. Exercise resulted in an increase in PC for both Microhydrin treatments with significantly greater PC compared to C. Total blood glutathione was unaffected by treatment or exercise. Exercise increased the ratio of oxidized to total glutathione and the MH II treatment resulted in a greater ratio compared to the other treatments. In conclusion, MH II results in lower blood lactate, while resulting in an increase in the concentration of oxidized protein and glutathione, suggesting heightened oxidative stress.
Andrew W. Subudhi, Scott L. Davis, Ronald W. Kipp, and E. Wayne Askew
The goal of this field study was to assess antioxidant status and markers of oxidative damage in elite alpine ski racers during routine training. Subjects included 12 members of the U.S. Men’s Alpine Ski Team attending a 10-day summer training camp. Blood draws were collected at rest and after exercise: (a) prior to training, (b) following 2 days of dry land training, and (c) after 4 days of on-snow skiing. Seven measures of antioxidant status were determined using colorimetric and HPLC methods (Trolox “equivalent antioxidant capacity, uric acid, α-tocopherol, β-tocopherol, total glutathione, cytosolic glutathione peroxidase, and superoxide dismutase). Oxidative stress was assessed using 2 markers of lipid peroxidation (malondialdehyde and lipid hydroperoxides) and 2 markers of protein oxidation (carbonylated total proteins and carbonylated hemoglobin). The results of this study suggest that antioxidant status of elite alpine skiers may decline over a period of intense training. However, elevations in markers of oxidative stress were not evident.
We investigated the effect of long-term treatment (6 wk) with selenium and vitamin E, in combination with aerobic exercise training, on malondialdehyde (MDA), oxidized low-density lipoprotein (ox-LDL), and glutathione peroxi-dase (GPx) in STZ-induced diabetic rats. The rats were assigned randomly to one of three treatment groups (n = 12 per group): 1) exercise group (EX), 2) selenium/vitamin E/exercise group (SVE), and 3) selenium/vitamin E group (SV). To estimate the acute effect of exercise, a 30-min endurance exercise was used. The MDA concentration was significantly lower in the SVE. The ox-LDL was significantly lower in the SVE and SV. The hepatic concentrations of selenium and vitamin E were significantly higher in the SVE. These results indicate that the increase in MDA is mildly attenuated in rats that were aerobically trained. Moreover, the joint administration of selenium and vitamin E with or without exercise training reduces the levels of ox-LDL.
Kyle L. Timmerman, Kevin D. Ballard, Michael A. Deal, Lisa C. Tagariello, Jenna M. Karrow, Gabrielle A. Volk, Adam Meisler, Ian D. Connors, and Rachael E. Mott
dismutase (SOD), glutathione peroxidase (GPx), and catalase, buffer ROS accumulation and are critical to limiting cellular oxidative damage. 10 Aging is linked to both increased ROS production 11 – 13 and diminished expression and activity of endogenous antioxidants. 14 , 15 This finding has generated