Effect of gender differences and voluntary exercise on antioxidant capacity in rats

The effects of gender difference and voluntary exercise on antioxidant capacity in rats were evaluated. The subjects were divided into two groups, physically active and sedentary. In the sedentary group, the level of hydroxyl radical in the liver was higher (P<0.001) in male rats than in female rats, however, in the physically active group, the level in male rats was lower (P<0.05) than in female rats. The levels of reduced glutathione (GSH) in physically active males and females were higher compared to those in the sedentary group. The physically active group also showed an increase in antioxidant enzymes, such as glutathione peroxidase (GPx), glutathione reductase (GR) and superoxide dismutase activities. The level of liver GSH was higher in physically active females than in physically active males. For both groups, GPx and GR activities in females were significantly higher than in males. These results indicate that female rats have an intrinsically higher antioxidant capacity, which resulted in increased levels of GSH via the glutathione redox cycle and gamma-glutamyl cycle enzymes. The adaptation to altered antioxidant capacity, induced by physical activity, appeared to be affected by gender differences.     

Nutritional deficiency, starvation, and tissue antioxidant status

Tissue antioxidant status may be compromised under conditions of dietary restriction, either as the result of a deficiency in a specific cofactor required by a particular antioxidant enzyme or of more complex alterations of a generalized nature triggered by metabolic responses to starvation. Many similarities exist between insulin-reversible abnormalities in tissue antioxidant enzyme activities seen in experimental diabetes and in animals subjected to food deprivation-induced weight loss which is associated with hypoinsulinemia. The complex alterations in tissue antioxidant enzyme activities resulting from nutritional deficiency states, disease or drug administration may have important clinical consequences. Free radical-related processes have been implicated in the pathology of certain conditions in which weight loss is frequently recommended (e.g., diabetes and atherosclerosis). It will be important to investigate the possible adverse effects of this intervention on the underlying disease process involved. Glutathione-dependent hepatic detoxification processes are impaired under conditions of nutritional deficiency. This finding not only has important clinical implications but the standard practice of fasting small laboratory animals overnight to ensure reliable drug absorption can markedly influence the results of pharmacological/toxicological experiments. Further studies of the influence of nutritional status on free radical-related processes are likely to yield valuable information which may be applicable to a variety of research and clinical problems.     

Cardiac adaptation to endurance exercise in rats

Endurance exercise is widely assumed to improve cardiac function in humans. This project has determined cardiac function following endurance exercise for 6 (n = 30) or 12 (n = 25) weeks in male Wistar rats (8 weeks old). The exercise protocol was 30 min/day at 0.8 km/h for 5 days/week with an endurance test on the 6th day by running at 1.2 km/h until exhaustion. Exercise endurance increased by 318% after 6 weeks and 609% after 12 weeks. Heart weight/kg body weight increased by 10.2% after 6 weeks and 24.1% after 12 weeks. Echocardiography after 12 weeks showed increases in left ventricular internal diameter in diastole (6.39 ± 0.32 to 7.90 ± 0.17 mm), systolic volume (49 ± 7 to 83 ± 11 μl) and cardiac output (75 ± 3 to 107 ± 8 ml/min) but not left wall thickness in diastole (1.74 ± 0.07 to 1.80 ± 0.06 mm). Isolated Langendorff hearts from trained rats displayed decreased left ventricular myocardial stiffness (22 ± 1.1 to 19.1 ± 0.3) and reduced purine efflux during pacing-induced workload increases. 31P-NMR spectroscopy in isolated hearts from trained rats showed decreased PCr and PCr/ATP ratios with increased creatine, AMP and ADP concentrations. Thus, this endurance exercise protocol resulted in physiological hypertrophy while maintaining or improving cardiac function. (Mol Cell Biochem 251: 51–59, 2003)     

Sex differences in endurance capacity and metabolic response to prolonged, heavy exercise

In order to test for possible sex differences in endurance capacity, groups of young, physically active women (n = 6) and men (n = 7) performed bicycle ergometer exercise at 80% and 90% of their maximal oxygen uptakes (VO2 max). The groups were matched for age and physical activity habits. At 80% VO2 max the women performed significantly longer (P less than 0.05), 53.8 +/- 12.7 min vs 36.8 +/- 12.2 min, respectively (means +/- SD). Mid-exercise and terminal respiratory exchange ratio (R) values were significantly lower in women, suggesting a later occurrence of muscle glycogen depletion as a factor in their enhanced endurance. At 90% VO2 max the endurance times were similar for men and women, 21.2 +/- 10.3 min and 22.0 +/- 5.0 min, respectively. The blood lactate levels reached in these experiments were only marginally lower (mean differences 1.5 to 2 mmol X l-1) than those obtained at VO2 max, suggesting high lactate levels as a factor in exhaustion. The changes in body weight during the 80% experiments and the degree of hemoconcentration were not significantly different between men and women.     

Skeletal muscle oxidative capacity, antioxidant enzymes, and exercise training

The purposes of this study were to determine whether exercise training induces increases in skeletal muscle antioxidant enzymes and to further characterize the relationship between oxidative capacity and antioxidant enzyme levels in skeletal muscle. Male Sprague-Dawley rats were exercise trained (ET) on a treadmill 2 h/day at 32 m/min (8% incline) 5 days/wk or were cage confined (sedentary control, S) for 12 wk. In both S and ET rats, catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) activities were directly correlated with the percentages of oxidative fibers in the six skeletal muscle samples studied. Muscles of ET rats had increased oxidative capacity and increased GPX activity compared with the same muscles of S rats. However, SOD activities were not different between ET and S rats, but CAT activities were lower in skeletal muscles of ET rats than in S rats. Exposure to 60 min of ischemia and 60 min of reperfusion (I/R) resulted in decreased GPX and increased CAT activities but had little or no effect on SOD activities in muscles from both S and ET rats. The I/R-induced increase in CAT activity was greater in muscles of ET than in muscles of S rats. Xanthine oxidase (XO), xanthine dehydrogenase (XD), and XO + XD activities after I/R were not related to muscle oxidative capacity and were similar in muscles of ET and S rats. It is concluded that although antioxidant enzyme activities are related to skeletal muscle oxidative capacity, the effects of exercise training on antioxidant enzymes in skeletal muscle cannot be predicted by measured changes in oxidative capacity.     

Selenium supplementation influences growth performance, antioxidant status and immune response in lambs

To investigate and compare the effect of inorganic and organic Se supplementation, 18 male lambs (24.68 ± 2.89 kg mean body weight, about 8–9 months of age) were divided into three groups of six animals in each, following randomized block design. While animals in the control group (Gr I) were fed a standard TMR containing 195 g/kg crushed maize grain, 175.5 g/kg soybean meal, 260 g/kg wheat bran, 13 g/kg mineral mixture (without Se), 6.5 g/kg common salt and 350 g/kg wheat straw, animals in Gr II and Gr III were additionally supplemented with 0.15 mg Se/kg of diet through sodium selenite (inorganic Se) and Jevsel-101 (organic Se), respectively. Experimental feeding was done for a period of 90 days. To assess the humoral immune response, all the lambs were intramuscularly inoculated with a single dose (2 mL) of Haemorrhagic septicaemia oil adjuvant vaccine on day 0; and blood samples were collected on day 0, 30, 60 and 90. Supplementation of Se had no effect on serum total cholesterol, total protein, albumin, globulin, albumin:globulin ratio, T₃, T₄, T₄:T₃ ratio; serum Ca and P levels and SGOT and SGPT activity. However, there was a significant increase in the serum Se level, RBC GSH-Px activity and humoral immune response in both the Se supplemented groups as compared to control group. Average daily gain (g) was highest (110) in Gr III, followed by Gr II (98.2) and lowest in Gr I (89.1). Thus, supplementation of organic as well as inorganic Se was found to improve the growth rate, humoral immune response and antioxidant status of the lambs; and between two sources, organic Se was more effective than inorganic Se.     

Carbon dioxide storage capacity of endurance and sprint-trained athletes in exercise

The purpose of this study was to compare CO2 storage capacity of endurance and sprint-trained athletes during steady state exercise. Ten subjects, five sprinters and five distance runners, performed a submaximal treadmill exercise at two different work rates, 45% and 65% of VO2max. CO2 storage capacity was determined by measuring the excess CO2 washout associated with hyperventilation, normalized for body weight and expressed per unit change in mixed venous PCO2 (ml kg-1 Torr-1). Mixed venous PCO2 (PvCO2) was measured by rebreathing equilibration. It was found that CO2 storage capacities of the runners were significantly (P less than 0.05) greater than the sprinters at the two work rates. The sprinters CO2 storage capacities were 2.69 and 2.14 ml kg-1 Torr-1 at low and high work rates, respectively. The corresponding mean values for the runners were 4.56 and 3.92 ml kg-1 Torr-1, respectively. These results may be explained by the metabolic differences between the sprinters and runners. The sprinters' musculature depends more heavily on the glycolytic metabolic pathway, which is associated with an increased lactate production and hence a reduction in the combining power of the blood for CO2 during exercise. At the low work rate, the body's storage capacity for CO2 was significantly (P less than 0.05) greater than the higher work rate for both groups. Obviously, at the higher work level more blood would be presented to the lungs per unit time allowing an increase in CO2 clearance from the body stores.     

Enhancement of arm exercise endurance capacity with dihydroxyacetone and pyruvate

The effects of dietary supplementation of dihydroxyacetone and pyruvate (DHAP) on endurance capacity and metabolic responses during arm exercise were determined in 10 untrained males (20-26 yr). Subjects performed arm ergometer exercise (60% peak O2 consumption) to exhaustion after consumption of standard diets (55% carbohydrate, 15% protein, 30% fat; 35 kcal/kg) containing either 100 g of Polycose (placebo, P) or DHAP (3:1, treatment) substituted for a portion of carbohydrate. The two diets were administered in a random order, and each was consumed for a 7-day period. Biopsy of the triceps muscle was obtained immediately before and after exercise. Blood samples were drawn through radial artery and axillary vein catheters at rest, after 60 min of exercise, and at exercise termination. Arm endurance was 133 +/- 20 min after P and 160 +/- 22 min after DHAP (P less than 0.01). Triceps glycogen at rest was 88 +/- 8 (P) and 130 +/- 19 mmol/kg (DHAP) (P less than 0.05). Whole arm arteriovenous glucose difference (mmol/l) was greater (P less than 0.05) for DHAP than P at rest (0.60 +/- 0.12 vs. 0.05 +/- 0.09) and after 60 min of exercise (1.00 +/- 0.12 vs. 0.36 +/- 0.11), but it did not differ at exhaustion. Neither respiratory exchange ratio nor respiratory quotient differed between trials at rest, after 60 min of exercise, or at exhaustion. Plasma free fatty acid, glycerol, beta-hydroxybutyrate, catecholamines, and insulin were similar during rest and exercise for both diets. Feeding DHAP for 7 days increased arm muscle glucose extraction before and during exercise, thereby enhancing submaximal arm endurance capacity.     

The effect of one year's swimming exercise on oxidant stress and antioxidant capacity in aged rats

The effect of exercise on oxidant stress and on alterations in antioxidant defense in elderly has been investigated extensively. However, the impact of regularly performed long-term physical activity starting from adulthood and prolonged up to the old age is not yet clear. We have investigated the changes in the activities of antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) - and lipid peroxidation in various tissues of rats which had performed (old-trained) or had not performed (old-control) regular swimming exercise for one year. These animals were compared with young-sedentary rats. Increased lipid peroxidation was observed with ageing in all tissues (heart, liver, kidney, striated muscle) and swimming had no additional effect on this elevation of lipid peroxidation. Heart and striated muscle SOD activites, and striated muscle CAT activity increased as a consequence of ageing, whereas kidney and liver CAT activities, as well as GPx activities in kidney, liver, lung and heart were significantly decreased compared to young controls. Lung and heart SOD, liver CAT activities as well as GPx activities in liver, lung and heart were increased significantly in rats which performed exercise during ageing, compared to the old-control group. These findings suggest that lifelong exercise can improve the antioxidant defense in many tissues without constituting any additional oxidant stress.     

Interactive effects of anemia and muscle oxidative capacity on exercise endurance

We used endurance training and acute anemia to assess the interactions among maximal oxygen consumption (VO2max), muscle oxidative capacity, and exercise endurance in rats. Animals were evaluated under four conditions: untrained and endurance-trained with each group subdivided into anemic (animals with reduced hemoglobin concentrations) and control (animals with unchanged hemoglobin concentrations). Anemia was induced by isovolemic plasma exchange transfusion. Hemoglobin concentration and hematocrit were decreased by 38 and 41%, respectively. Whole body VO2max was decreased by 18% by anemia regardless of training condition. Anemia significantly reduced endurance by 78% in untrained rats but only 39% in trained animals. Endurance training resulted in a 10% increase in VO2max, a 75% increase in the distance run to exhaustion, and 35, 45, and 58% increases in skeletal muscle pyruvate-malate, alpha-ketoglutarate, and palmitylcarnitine oxidase activities, respectively. We conclude that endurance is related to the interactive effects of whole body VO2max and muscle oxidative capacities for the following reasons: 1) anemic untrained and trained animals had similar VO2max but trained rats had higher muscle oxidative capacities and greater endurance; 2) regardless of training status, the effect of acute anemia was to decrease VO2max and endurance; and 3) trained anemic rats had lower VO2max but had greater muscle oxidative capacity and greater endurance than untrained controls.     

Effect of cocaine on exercise endurance and glycogen use in rats

To determine the effects of cocaine on exercise endurance, male rats were injected intraperitoneally with cocaine (20 mg/kg body wt) or saline and then run to exhaustion 20 min later at 22 m/min and 15% grade. Saline-injected animals ran 74.9 +/- 16.5 (SD) min, whereas cocaine-treated rats ran only 29 +/- 11.6 min. The drug had no effect on resting blood glucose or lactate levels, nor did it affect resting glycogen levels in liver or red and white vastus muscle. However, it did reduce resting soleus glycogen content by 30%. During exercise liver and soleus glycogen depletion occurred at the same rate in saline- and cocaine-treated animals. In contrast, the rate of glycogen depletion during exercise in red and white vastus was markedly increased in cocaine-treated rats with a corresponding elevation in blood lactate (12 vs. only 5 mM in saline group) at exhaustion. These data suggest that cocaine administration (20 mg/kg) before submaximal exercise dramatically alters glycogen metabolism during exercise, and this effect has a negative impact on exercise endurance.     

Relation between cycling exercise capacity, fiber-type composition, and lower extremity muscle strength and muscle endurance

The aim of the study was to determine the relation between peak oxygen uptake V(O2)peak), peak work rate (WRpeak), fiber-type composition, and lower extremity strength and endurance during a maximal incremental cycle test. Thirty-nine healthy sedentary men, aged 30-46, participated in the study. Subjects performed a maximal incremental cycle test and isokinetic knee extension (KE) and flexion (KF) strength and endurance tests at velocities of 60 and 180° · s(-1). Muscle biopsies were taken from m. vastus lateralis and analyzed for fiber-type composition. A significant correlation existed between KE strength and V(O2)peak and WRpeak. Also, KF endurance correlated significantly to V(O2)peak and WRpeak. The KE endurance correlated significantly to WRpeak (rp = 0.32, p < 0.05) and almost significantly to V(O2)peak (rp = 0.28, p = 0.06). Stepwise multiple regression analyses showed that KE strength, KF endurance, and the percentage of type I fibers could explain up to 40% of the variation in V(O2) and WRpeak. The performance of sedentary subjects in a maximal incremental cycle test is highly affected by knee muscle strength and endurance. Fiber-type composition also contributes but to a smaller extent.     

Effect of heliox on lung dynamic hyperinflation, dyspnea, and exercise endurance capacity in COPD patients.

We tested the hypothesis that heliox breathing, by reducing lung dynamic hyperinflation (DH) and dyspnea (Dys) sensation, may significantly improve exercise endurance capacity in patients with chronic obstructive pulmonary disease [n = 12, forced expiratory volume in 1 s = 1.15 (SD 0.32) liters]. Each subject underwent two cycle ergometer high-intensity constant work rate exercises to exhaustion, one on room air and one on heliox (79% He-21% O2). Minute ventilation (VE), carbon dioxide output, heart rate, inspiratory capacity (IC), Dys, and arterial partial pressure of CO2 were measured. Exercise endurance time increased significantly with heliox [9.0 (SD 4.5) vs. 4.2 (SD 2.0) min; P < 0.001]. This was associated with a significant reduction in lung DH at isotime (Iso), as reflected by the increase in IC [1.97 (SD 0.40) vs. 1.77 (SD 0.41) liters; P < 0.001] and a decrease in Dys [6 (SD 1) vs. 8 (SD 1) score; P < 0.001]. Heliox induced a state of relative hyperventilation, as reflected by the increase in VE [38.3 (SD 7.7) vs. 35.5 (SD 8.8) l/min; P < 0.01] and VE/carbon dioxide output [36.3 (SD 6.0) vs. 33.9 (SD 5.6); P < 0.01] at peak exercise and by the reduction in arterial partial pressure of CO2 at Iso [44 (SD 6) vs. 48 (SD 6) Torr; P < 0.05] and at peak exercise [46 (SD 6) vs. 48 (SD 6) Torr; P < 0.05]. The reduction in Dys at Iso correlated significantly (R = -0.75; P < 0.01) with the increase in IC induced by heliox. The increment induced by heliox in exercise endurance time correlated significantly with resting increment in resting forced expiratory in 1 s (R = 0.88; P < 0.01), increase in IC at Iso (R = 0.70; P < 0.02), and reduction in Dys at Iso (R = -0.71; P < 0.01). In chronic obstructive pulmonary disease, heliox breathing improves high-intensity exercise endurance capacity by increasing maximal ventilatory capacity and by reducing lung DH and Dys.     

Hydrogen improves exercise endurance in rats by promoting mitochondrial biogenesis

BackgroundPrevious studies have shown that hydrogen water has antioxidant and anti-inflammatory effects on exercise-induced fatigue; however, its molecular mechanism remains unclear.MethodsAdult male Sprague-Dawley rats were randomly divided into a pure water drinking group (NC) and a hydrogen water drinking group (HW) (n = 7), and 2-week treadmill training was used to establish a sports model. Gut bacterial community profiling was performed using 16S rRNA gene sequencing analysis. The expression levels of mitochondrial energy metabolism-related genes and the levels of sugar metabolites and enzymes were measured.ResultsThe exercise tolerance of rats in the HW group significantly improved, and the distribution and diversity of intestinal microbes were altered. Hydrogen significantly upregulated genes related to mitochondrial biogenesis, possibly via the Pparγ/Pgc-1α/Tfam pathway. In addition, hydrogen effectively mediated the reprogramming of skeletal muscle glucose metabolism.ConclusionOur findings establish a critical role for hydrogen in improving endurance exercise performance by promoting mitochondrial biogenesis via the Pparγ/Pgc-1α/Tfam pathway.     

Effect of antioxidant supplementation on insulin sensitivity in response to endurance exercise training

While production of reactive oxygen and nitrogen species (RONS) is associated with some of the beneficial adaptations to regular physical exercise, it is not established whether RONS play a role in the improved insulin-stimulated glucose uptake in skeletal muscle obtained by endurance training. To assess the effect of antioxidant supplementation during endurance training on insulin-stimulated glucose uptake, 21 young healthy (age 29 ± 1 y, BMI 25 ± 3 kg/m(2)) men were randomly assigned to either an antioxidant [AO; 500 mg vitamin C and 400 IU vitamin E (α-tocopherol) daily] or a placebo (PL) group that both underwent a supervised intense endurance-training program 5 times/wk for 12 wk. A 3-h euglycemic-hyperinsulinemic clamp, a maximal oxygen consumption (Vo(2max)) and maximal power output (P(max)) test, and body composition measurements (fat mass, fat-free mass) were performed before and after the training. Muscle biopsies were obtained for determination of the concentration and activity of proteins regulating glucose metabolism. Although plasma levels of vitamin C (P < 0.05) and α-tocopherol (P < 0.05) increased markedly in the AO group, insulin-stimulated glucose uptake increased similarly in both the AO (17.2%, P < 0.05) and the PL (18.9%, P < 0.05) group in response to training. Vo(2max) and P(max) also increased similarly in both groups (time effect, P < 0.0001 for both) as well as protein content of GLUT4, hexokinase II, and total Akt (time effect, P ≤ 0.05 for all). Our results indicate that administration of antioxidants during strenuous endurance training has no effect on the training-induced increase in insulin sensitivity in healthy individuals.     

Enhanced testicular antioxidant capacity in streptozotocin-induced diabetic rats

Diabetes mellitus is associated with diabetic impairment of testicular function, ultimately leading to reduced fertility. Its etiology may involve oxidative damage by reactive oxygen substances, and protection against this damage can be offered by antioxidant supplementation. The aim of this study was to investigate the effects of intraperitoneal administration of vitamin C and E, selenium (Se), and vitamin E plus Se (COM) on concentrations of lipid peroxide (as malondialdehyde; MDA), reduced glutathione (GSH), and vitamin E concentrations and glutathione peroxidase (GSH-Px) activity in the testes of rats with diabetes induced by streptozotocin (STZ). Sixty groups were used (10 animals each) and these animals were initially allocated to two groups: control group and diabetic group. The diabetic group was subdivided into five groups as follows: diabetic control (DC), vitamin E, Se, COM, and vitamin C. Animals in the DC group and vitamin C, vitamin E, Se, and COM groups were made diabetic by the injection of STZ on 4 d after an injection of vitamins C and E, Se, and COM. Those vitamins and Se were also administered for 21 consecutive days. The MDA, vitamin E, GSH levels, and GSH-Px activities in testes were determined. Although the vitamin E concentration was higher in the control than in the DC group, the MDA levels were found to be lower in the control than in the DC group. The MDA levels in the testes samples of vitamin C, vitamin E, Se, and COM groups were lower than the DC group. However, GSH-Px activity and GSH levels in the testes were not significantly different between the control and DC groups. Vitamin E concentrations in the vitamin C, vitamin E, Se, and COM groups and GSH levels and GSH-Px activities in the Se, COM, and vitamin C groups were higher than either the control or DC group. The results indicate that reactive oxygen substances may be involved in possible testicular complications in diabetes of rats. Administration of vitamins C and E and Se reduced the testicular lipid peroxidation; these vitamins and Se had significant protective effects on testes of rats against oxidative damage in diabetes. Abstract of the study was presented at the conference Trace Elements in Men and Animals-11. June 2–6, 2002; Dr. Naziroğlu has been awarded a TEMA11 Investigative Scientist Award.     

Influence of carbohydrate status on immune responses before and after endurance exercise

To determine the effect of carbohydrate (CHO)status on immune responses after long-duration exercise, on twooccasions, 10 men completed a glycogen-depleting bout of cycleergometry followed by 48 h of either a high-CHO diet (HiCHO; 8.0 gCHO/kg) or a low-CHO diet (LoCHO; 0.5 g CHO/kg). After the 48 h,subjects completed a 60-min ride at 75% maximalO₂ uptake (EX). Blood samples were taken predepletion, pre-EX, post-EX, and 2 and 24 h post-EX and wereassayed for leukocyte number and function, glucose, glutamine, andcortisol. The glucose responses were significantly higher in the HiCHO(4.62 ± 0.26 mM) vs. the LoCHO (3.19 ± 0.15 mM) condition post-EX, and glutamine was significantly higher in the HiCHO(0.472 ± 0.036 mM) vs. the LoCHO (0.410 ± 0.025 mM)condition throughout. Cortisol levels were significantly greater in theLoCHO (587 ± 50 nM) vs. the HiCHO (515 ± 62 nM) conditionthroughout the trial. Lymphocyte proliferation (phytohemagglutinin) wassignificantly depressed after exercise. However, there was nodifference between conditions, and the depression was not correlatedwith elevations in cortisol. Circulating numbers of leukocytes,neutrophils, lymphocytes, and lymphocyte subsets were significantlygreater in the LoCHO vs. the HiCHO condition at the post-EX and 2 hpost-EX time points. These data indicate that the exercise and dietmanipulation altered the number of circulating leukocytes but did notaffect the decrease in lymphocyte proliferation that occurred afterexercise.