Antioxidants and oxidative stress in exercise

Strenuous exercise increases oxygen consumption and causes disturbance of intracellular pro-oxidant-antioxidant homeostasis. The mitochondrial electron transport chain, polymorphoneutrophil, and xanthine oxidase have been identified as major sources of intracellular free radical generation during exercise. Reactive oxygen species pose a serious threat to the cellular antioxidant defense system, such as diminished reserve of antioxidant vitamins and glutathione, and increased tissue susceptibility to oxidative damage. However, enzymatic and nonenzymatic antioxidants have demonstrated great adaptation to acute and chronic exercise. The delicate balance between pro-oxidants and antioxidants suggests that supplementation of antioxidants may be desirable for physically active individuals under certain physiological conditions by providing a larger protective margin.     

Habitual exercise induced resistance to oxidative stress

We investigated whether habitual exercise (HE) modulates levels of oxidative DNA damage and responsiveness to oxidative stress induced by renal carcinogen Fe-nitrilotriacetic acid (Fe-NTA). During a ten week protocol, two groups of rats either remained sedentary or underwent swimming for 15-60 min per day, 5 days per week, with or without a weight equivalent to 5% of their body weight. Then we injected Fe-NTA and sacrificed the rats 1 h after the injection. We determined the activity of superoxide dismutase (SOD) in diaphragm and kidney, evaluated levels of 8-hydroxydeoxyguanosine (8OHdG), catalase, and glutathione peroxidase, and assayed OGG1 protein levels in kidney. SOD activity in the diaphragm and kidney was increased in HE rats. By itself, HE had no effect on the level of 8OHdG, but it did significantly suppress induction of 8OHdG by Fe-NTA, and the amount of suppression correlated with intensity of exercise. These results suggest that HE induces resistance to oxidative stress and, at least at the initiation stage, inhibits carcinogenesis.     

Habitual exercise induced resistance to oxidative stress

We investigated whether habitual exercise (HE) modulates levels of oxidative DNA damage and responsiveness to oxidative stress induced by renal carcinogen Fe-nitrilotriacetic acid (Fe-NTA). During a ten week protocol, two groups of rats either remained sedentary or underwent swimming for 15–60?min per day, 5 days per week, with or without a weight equivalent to 5% of their body weight. Then we injected Fe-NTA and sacrificed the rats 1?h after the injection. We determined the activity of superoxide dismutase (SOD) in diaphragm and kidney, evaluated levels of 8-hydroxydeoxyguanosine (8OHdG), catalase, and glutathione peroxidase, and assayed OGG1 protein levels in kidney. SOD activity in the diaphragm and kidney was increased in HE rats. By itself, HE had no effect on the level of 8OHdG, but it did significantly suppress induction of 8OHdG by Fe-NTA, and the amount of suppression correlated with intensity of exercise. These results suggest that HE induces resistance to oxidative stress and, at least at the initiation stage, inhibits carcinogenesis.     

Oxidative stress associated with exercise,psychological stress and life-style factors

Oxidative stress is a cellular or physiological condition of elevated concentrations of reactive oxygen species that cause molecular damage to vital structures and functions. Several factors influence the susceptibility to oxidative stress by affecting the antioxidant status or free oxygen radical generation. Here, we review the effect of alcohol, air pollution, cigarette smoke, diet, exercise, non-ionizing radiation (UV and microwaves) and psychological stress on the development of oxidative stress.Regular exercise and carbohydrate-rich diets seem to increase the resistance against oxidative stress. Air pollution, alcohol, cigarette smoke, non-ionizing radiation and psychological stress seem to increase oxidative stress. Alcohol in lower doses may act as an antioxidant on low density lipoproteins and thereby have an anti-atherosclerotic property.     

Oxidative stress in athletes during extreme endurance exercise

Despite the many known health benefits of exercise, there is a body of evidence suggesting that endurance exercise is associated with oxidative stress. To determine whether extreme endurance exercise induces lipid peroxidation, 11 athletes (3 females, 8 males) were studied during a 50 km ultramarathon (trial 1) and during a sedentary protocol (trial 2) 1 month later. The evening before each trial, with dinner, subjects consumed 75 mg each d(3)-RRR and d(6)-all rac-alpha-tocopheryl acetates. Blood was obtained at baseline, 30 min pre-race, mid-race, post-race, 1 h post-race, 24 h post-race, and at corresponding times during trial 2. All 11 subjects completed the race; average run time was 391 +/- 23 min. Plasma F(2)-isoprostanes increased from 75 +/- 7 pg/ml at pre-race to 131 +/- 17 (p <.02) at post-race, then returned to baseline at 24 h post-race; F(2)-isoprostanes were unchanged during trial 2. Deuterated alpha-tocopherol disappearance rates were faster (2.8 x 10(-4) +/- 0.2 x 10(-4)) during the race compared to the sedentary trial (2.3 x 10(-4) +/- 0.2 x 10(-4); p <.03). These data suggest that extreme endurance exercise results in the generation of lipid peroxidation with a concomitant increase in vitamin E disappearance.     

Assessment of oxidative stress in lymphocytes with exercise

This study investigated whether changes in the cellular composition of blood during exercise could partly account for observations of exercise-induced changes in lymphocyte oxidative stress markers. Markers of oxidative stress were assessed before and after 60 min of intense treadmill running. Samples were collected from 16 men (means ± SD: age 33 ± 13 yr; body mass index 23.8 ± 2.5 kg/m(2); maximal oxygen uptake 59.7 ± 5.2 ml·kg(-1)·min(-1)). Peripheral blood lymphocytes were assayed for protein carbonyl concentration, and plasma was assessed for lipid peroxides and antioxidant capacity. In a separate study, intracellular thiol concentration was determined in lymphocyte subsets from eight characteristically similar men by flow cytometry, of which T-cell memory populations were further identified on the basis of CD27, CD28, and CD45RA expression. Total lymphocyte protein carbonyls were transiently increased with exercise and returned to baseline within 15 min (P < 0.001). This change was accompanied by an increase in plasma lipid peroxides (P < 0.05) and total antioxidant capacity (P < 0.001). Correlation analyses showed that lymphocyte protein carbonyl content was not related to changes in the cellular composition of peripheral blood during exercise. Natural killer cells (CD3(-)CD56(+)) and late-differentiated/effector memory cells (CD4(+)/CD8(+)CD27(-)CD28(-)/CD45RA(+)), which mobilized most with exercise, showed high intracellular thiol content (P < 0.001). High thiol content suggests a lower oxidative load carried by these lymphocytes. Thus vigorous exercise resulted in a transient increase in lymphocyte oxidative stress. Results suggest this was unrelated to the alterations in the cellular composition of peripheral blood.     

Oxidative stress and delayed-onset muscle damage after exercise

Reactive oxygen species (ROS) produced during exercise may be involved in delayed-onset muscle damage related to inflammation. To investigate this hypothesis, we studied whether oxidative stress increases nuclear translocation of nuclear factor-kappaB and chemokine expression in skeletal muscle using myotube L6 cells. We also assessed whether prolonged acute exercise could increase these parameters in rats. In L6 cells, H(2)O(2) induced nuclear translocation of p65 and increased the expression of cytokine-induced neutrophil chemoattractant-1 (CINC-1) and monocyte chemoattractant protein-1 (MCP-1), whereas preincubation with alpha-tocopherol limited the increase in these proteins. Sprague Dawley rats were divided into the following groups: rested control, exercised, rested with a high alpha-tocopherol diet, and exercised with a high alpha-tocopherol diet. After 3 weeks of acclimation, both exercise groups ran on a treadmill at 25 m/min for 60 min. Exercise increased nuclear p65, CINC-1, and MCP-1 in gastrocnemius muscle cells, but these changes were ameliorated by the high alpha-tocopherol diet. Increases in myeloperoxidase and thiobarbituric acid-reactive substrates were ameliorated by a high alpha-tocopherol diet, as were the histological changes. Neutrophil activity was not altered by either exercise or a high alpha-tocopherol diet. These results indicate that delayed-onset muscle damage induced by prolonged exercise is partly related to inflammation via phagocyte infiltration caused by ROS and that alpha-tocopherol (an antioxidant) can attenuate such inflammatory changes.     

Plasmatic markers of muscular stress in isokinetic exercise

In this paper we examined the variations of plasmatic concentrations of hypoxanthine and xanthine, and their relation with other important indicators of muscular stress creatine-kinase (CK), myoglobin, uric acid, leucocytes, in prolonged, isokynetic physical exercise, performed in a concentric mode at different joint excursion. Twenty healthy male subjects performed isokinetic exercises in concentric-concentric mode, with joint excursion of 30, 60, 90 deg/sec. Blood samples were drawn at rest, immediately after exercise and after 45 min of recovery. The plasmatic concentration of hypoxanthine increased at the end of physical exercise, compared to the rest value of about 1,5 micromol/L, up to a level of greater than 19 micromol/L; the values were higher after a period of recovery of 45 min and the increase varies considerably according to the type of exercise that was performed. Myoglobin has a slight but sensible increment too, with the same trend as hypoxanthine, while CK increase without correlation to the type of exercises. The relation with other indicators of muscular activity demonstrates that in none of the different isokinetic exercises, performed at concentric mode, was there ultrastructural damage, while it is possible to come across a considerable metabolic stress, which is dissimilar in the different kinds of exercises. The results suggest that hypoxanthine can be useful in monitoring the effectiveness of a work load and the metabolic stress consequences on the muscle tissue in training or rehabilitation programs. The results also suggest that even myoglobin, at small concentrations, can have the same function.     

Arm exercise stress perfusion imaging predicts clinical outcome

Treadmill exercise capacity in resting metabolic equivalents (METs) and stress hemodynamic, electrocardiographic (ECG), and myocardial perfusion imaging (MPI) responses are independently predictive of adverse clinical events. However, limited data exist for arm ergometer stress testing (AXT) in patients who cannot perform leg exercise because of lower extremity disabilities. We sought to determine the extent to which AXT METs, hemodynamic, ECG, and MPI responses to arm exercise add independent incremental value to demographic and clinical variables for prediction of all-cause mortality, myocardial infarction (MI), or late coronary revascularization, individually or as a composite. A prospective cohort of 186 patients aged 64 ± 10 (SD) yr, unable to perform lower extremity exercise, underwent AXT MPI for clinical reasons between 1997 and 2002, and were followed for 62 ± 23 mo, to an endpoint of death or 12/31/2006. Average annual rates were 5.4% for mortality, 2.2% for MI, 2.5% for late coronary revascularization, and 8.0% for combined events. After adjustment for age and clinical variables, AXT METs [P < 0.05; hazard ratio (HR) = 0.59; confidence interval (CI) = 0.35-0.84] and abnormal MPI (P < 0.01; HR = 2.48; CI = 2.15-2.81) were independently predictive of mortality. A positive AXT ECG (P < 0.05; HR = 2.61; CI = 2.13-3.10) was predictive of MI. Death and MI combined were prognosticated by METs (P < 0.05; HR = 0.63; CI = 0.41-0.85), MPI (P < 0.05; HR = 1.77; CI = 1.49-2.05), and a positive AXT ECG (P < 0.05; HR = 1.86; CI = 1.55-2.17). In conclusion, for high risk older patients who cannot perform leg exercise because of lower extremity disabilities, AXT METs are as important as MPI for prediction of mortality alone and death and MI combined, and a positive AXT ECG prognosticates MI alone and death and MI combined.     

Effect of heat stress on glucose kinetics during exercise

Hargreaves, Mark, Damien Angus, Kirsten Howlett, Nelly MarmyConus, and Mark Febbraio. Effect of heat stress on glucose kinetics during exercise. J. Appl.Physiol. 81(4): 1594-1597, 1996.To identify themechanism underlying the exaggerated hyperglycemia during exercise inthe heat, six trained men were studied during 40 min of cyclingexercise at a workload requiring 65% peak pulmonary oxygen uptake(O_{2 peak}) on twooccasions at least 1 wk apart. On one occasion, the ambient temperaturewas 20°C [control (Con)], whereas on the other, it was40°C [high temperature (HT)]. Rates ofglucose appearance and disappearance were measured by using a primedcontinuous infusion of[6,6-²H]glucose. Nodifferences in oxygen uptake during exercise were observed betweentrials. After 40 min of exercise, heart rate, rectal temperature,respiratory exchange ratio, and plasma lactate were all higher in HTcompared with Con (P < 0.05). Plasmaglucose levels were similar at rest (Con, 4.54 ± 0.19 mmol/l; HT,4.81 ± 0.19 mmol/l) but increased to a greater extent duringexercise in HT (6.96 ± 0.16) compared with Con (5.45 ± 0.18;P < 0.05). This was the result of ahigher glucose rate of appearance in HT during the last 30 min ofexercise. In contrast, the glucose rate of disappearance and metabolicclearance rate were not different at any time point during exercise.Plasma catecholamines were higher after 10 and 40 min of exercise in HTcompared with Con (P < 0.05),whereas plasma glucagon, cortisol, and growth hormone were higher in HTafter 40 min. These results indicate that the hyperglycemia observedduring exercise in the heat is caused by an increase in liver glucoseoutput without any change in whole body glucoseutilization.

     

Oxidative stress during exercise: Implication of antioxidant nutrients

Research evidence has accumulated in the past decade that strenuous aerobic exercise is associated with oxidative stress and tissue damage in the body. There is indication that generation of oxygen free radicals and other reactive oxygen species may be the underlying mechanism for exercise-induced oxidative damage, but a causal relationship remains to be established. Enzymatic and nonenzymatic antioxidants play a vital role in protecting tissues from excessive oxidative damage during exercise. Depletion of each of the antioxidant systems increases the vulnerability of various tissues and cellular components to reactive oxygen species. Because acute strenuous exercise and chronic exercise training increase the consumption of various antioxidants, it is conceivable that dietary supplementation of specific antioxidants would be beneficial.     

Early contributions of Russian stress and exercise physiologists.

In Russia, the free development of scientific ideas was suppressed in 1950 as a result of the actions of the Joint Session of the Academy of Sciences and the Academy of Medical Sciences of the USSR. Hans Selye's theory on the general adaptation syndrome was considered unscientific. From 1956 to 1958, Pjotr Anokhin and Pjotr Gorizontov presented definitive arguments for having the theory accepted by scientists while the significance of hormones in adaptation became a topic of endocrine studies (Boris Aleshin, Igor Eskin, Vassily Komissarenko, Samuel Leites, and Michael Kolpakov). Later, Felius Meerson made essential contributions to the adaptive significance of protein synthesis and stress-limiting systems. The area of exercise physiology dealing with acute and chronic adaptation to strong physiological stressors was founded by Leon Orbeli and developed by Aleksei Krestovnikov. Significant contributors to this area were Vladimir Farfel, Nikolai Yakovlev, and Nikolai Zimkin. Although the majority of their publications have remained unknown outside of Russia, it is interesting that many of their results have been "rediscovered" by others. Yakovlev also deserves recognition because he was among the founders of contemporary exercise biochemistry and because his research has provided the foundation for current investigations. Several generations of young scientists have been inspired by the above-mentioned Russian scientists. Today, however, the research activities of scientists are no longer limited by political pressures but by financial resources instead.     

Plasma volume during heat stress and exercise in women

Five women were studied during exercise and passive heating to determine whether PV dynamics were affected by the menstrual cycle. The exercise bout (80% VO2 peak) on a modified cycle ergometer and the passive heat stress were done in a hot environment (Ta = 50 degrees C, Pw = 1.61 kPa) during the follicular and luteal phase. Esophageal temperature (Tes) was measured continuously. Blood samples were drawn after each 0.2 degree C increase in Tes and VO2 was measured at that time. Initial PV was estimated at rest during the follicular phase. PV changes from rest were calculated at each Tes from Hb and Hct. During passive heating, PV decreased by a mean volume of 156 (+/- 80) ml to 2.83 (+/- 0.09) l in the follicular phase. During the luteal phase, there was a larger volume reduction (300 +/- 100 ml) during passive heating, and the final PV was lower than in the follicular phase and averaged 2.47 +/- 0.18 l. During exercise, PV decreased 463 (+/- 90) ml to 2.50 (+/- 0.11) l in the follicular and 381 (+/- 70) ml to 2.50 (+/- 0.23) l in the luteal phase. These data indicate that there is a menstrual cycle effect on PV dynamics during passive heating such that more fluid is shifted out of the vasculature during the luteal phase. During severe exercise there is a greater fluid loss during the follicular phase, yet the final PV is not different between phases.     

The cardiac filling pressure following exercise and thermal stress

Under heat stress, a decrease of the central venous pressure (CVP) was regularly observed, raising the question of whether this reaction is a limiting factor for the circulation. In animal experiments it could be shown, however, that despite a lowered CVP, which depended on the elevated body temperatures, a high cardiac output (CO), as well as an elevated stroke volume could be maintained. A low CVP went hand in hand with a low total peripheral resistance. It was argued that under these circumstances the low CVP was not limiting because the intrinsic factors of the heart (sympathetic stimulation) were capable of maintaining a high CO. In human experiments the lowered CVP had to be seen in relation to the degree of dehydration. Regardless of whether the plasma volume remained constant, as in exercise, or declined, as in thermal stress (sauna), the CVP followed the volume depletion of the vascular and extravascular space, and it might well be that under these circumstances CVP is limiting. In this case, however, the altered CVP must be seen first as a monitor for the fluid deficit and not as a factor controlling cardiac function.     

Mitogenic response of T-lymphocytes to exercise training and stress

The impact of exercise training and stress on the immune response was examined by measuring the mitogenic response of spleen lymphocytes to the T-cell mitogen concanavalin A (Con-A). Male Sprague-Dawley rats were divided into four groups: sedentary controls (n = 11), handled controls (n = 12), treadmill runners (n = 10), and voluntary runners (n = 11) housed in running wheels. The treadmill group ran at 22 m/min (0.8 mph) for 45 min, 5 days/wk for 8 wk. After the training period, spleen lymphocytes isolated from each rat were incubated with Con-A for 54 h, pulsed with radiolabeled thymidine for 18 h, and counted for tritium activity. Counts per minute per group (means +/- SE) were as follows: sedentary, 6,839 +/- 1,461; handled, 8,959 +/- 1,576; voluntary runners, 13,126 +/- 2,069; and treadmill runners, 18,950 +/- 5,975. One-way analysis of variance and Tukey's highly significant difference test found the counts per minute of the treadmill runners to be significantly different from the counts per minute of the sedentary animals. These results indicate that the responsiveness of spleen lymphocytes to Con-A increases as the level of stress and exercise increases.