HSP72 as a complementary protection against oxidative stress induced by exercise in the soleus muscle of rats

Given the potential of reactive oxygen species to damage intracellular proteins during subsequent bouts of muscle contractions, it was suggested that, when this production exceeds the antioxidant capacity, the preexisting antioxidant pathways may be complemented by the synthesis of the defense mechanism represented by heat shock proteins (HSPs), stress proteins with the function of repair and maintaining protein folding. To test this hypothesis, we analyzed reactive carbonyl derivatives in plasma and the expression of HSP72 and activities of enzymes from the oxidative and antioxidant defense systems in the soleus muscle of sedentary rats and rats trained by two protocols: continuous and intermittent. We analyzed all three groups at rest and 2 h after acute exercise. After 8 wk of training, the animals from both groups clearly demonstrated higher resistance to exercise. Both trained groups showed significantly higher citrate synthase, catalase, and glutathione reductase activities than the control group (P < 0.01). After acute exercise, catalase and glutathione reductase activities significantly decreased (P < 0.01) and plasma reactive carbonyl derivatives significantly increased (P < 0.05) in the sedentary group, suggesting an oxidative-stress condition as responsible for exhaustion in this group. Finally, after acute exercise, the induction of HSP72 expression occurred only in the sedentary group, suggesting that HSP72 acts as a complementary protective mechanism in exercise-induced oxidative stress.     

Effects of endurance training and acute exhaustive exercise on antioxidant defense mechanisms in rat heart

We investigated whether 8-week treadmill training strengthens antioxidant enzymes and decreases lipid peroxidation in rat heart. The effects of acute exhaustive exercise were also investigated. Male rats (Rattus norvegicus, Sprague-Dawley strain) were divided into trained and untrained groups. Both groups were further divided equally into two groups where the rats were studied at rest and immediately after exhaustive exercise. Endurance training consisted of treadmill running 1.5 h day(-1), 5 days week(-1) for 8 weeks. For acute exhaustive exercise, graded treadmill running was conducted. Malondialdehyde level in heart tissue was not affected by acute exhaustive exercise in untrained and trained rats. The activities of glutathione peroxidase and glutathione reductase enzymes decreased by both acute exercise and training. Glutathione S-transferase and catalase activities were not affected. Total and non-enzymatic superoxide scavenger activities were not affected either. Superoxide dismutase activity decreased by acute exercise in untrained rats; however, this decrease was not observed in trained rats. Our results suggested that rat heart has sufficient antioxidant enzyme capacity to cope with exercise-induced oxidative stress, and adaptive changes in antioxidant enzymes due to endurance training are limited.     

The Anabolic Androgenic Steroid Nandrolone Decanoate Disrupts Redox Homeostasis in Liver,Heart and Kidney of Male Wistar Rats

The abuse of anabolic androgenic steroids (AAS) may cause side effects in several tissues. Oxidative stress is linked to the pathophysiology of most of these alterations, being involved in fibrosis, cellular proliferation, tumorigenesis, amongst others. Thus, the aim of this study was to determine the impact of supraphysiological doses of nandrolone decanoate (DECA) on the redox balance of liver, heart and kidney. Wistar male rats were treated with intramuscular injections of vehicle or DECA (1 mg.100 g⁻¹ body weight) once a week for 8 weeks. The activity and mRNA levels of NADPH Oxidase (NOX), and the activity of catalase, glutathione peroxidase (GPx) and total superoxide dismutase (SOD), as well as the reduced thiol and carbonyl residue proteins, were measured in liver, heart and kidney. DECA treatment increased NOX activity in heart and liver, but NOX2 mRNA levels were only increased in heart. Liver catalase and SOD activities were decreased in the DECA-treated group, but only catalase activity was decreased in the kidney. No differences were detected in GPx activity. Thiol residues were decreased in the liver and kidney of treated animals in comparison to the control group, while carbonyl residues were increased in the kidney after the treatment. Taken together, our results show that chronically administered DECA is able to disrupt the cellular redox balance, leading to an oxidative stress state.     

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.     

Protective effects of long term dietary restriction on swimming exercise-induced oxidative stress in the liver, heart and kidney of rat

In this study, we evaluated the hypothesis that long term dietary restriction would have beneficial effects on the oxidative stress and antioxidant enzyme systems in liver, heart and kidney in adult male rats undergoing different intensities of swimming exercise. Sixty male, Sprague-Dawley rats were assigned as either dietary restricted on every other week day (DR) or fed ad libitum (AL) groups, and each group was further subdivided into sedentary, endurance swimming exercise training (submaximal exercise) and exhaustive swimming exercise (maximal exercise) groups. Animals in the submaximal exercise group swam 5 days/week for 8 weeks, while maximal exercise was performed as an acute bout of exercise. In parallel with the increase in the intensity of the exercise, the degree of lipid peroxidation and protein oxidation were increased in both the DR and AL groups; however the rate of increase was lower in the DR group. Reduced glutathione (GSH), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) enzyme activities were lower in the DR group than in the AL group. In parallel with the increase in exercise intensity, GSH and GR enzyme activities decreased, whereas an increase was observed in GSH-Px enzyme activity. In conclusion, the comparison between the DR and AL groups with the three swimming exercise conditions shows that the DR group is greatly protected against different swimming exercise-induced oxidative stress compared with the AL group.     

Physiological and biochemical correlates of increased work in trained iron-deficient rats

We investigated physiological and biochemical factors associated with the improved work capacity of trained iron-deficient rats. Female 21-day-old rats were assigned to one of four groups, two dietary groups (50 and 6 ppm dietary iron) subdivided into two levels of activity (sedentary and treadmill trained). Iron deficiency decreased hemoglobin (61%), maximal O2 uptake. (VO2max) (40%), skeletal muscle mitochondrial oxidase activities (59-90%), and running endurance (94%). In contrast, activities of tricarboxylic acid (TCA) cycle enzymes in skeletal muscle were largely unaffected. Four weeks of mild training in iron-deficient rats resulted in improved blood lactate homeostasis during exercise and increased VO2max (15%), TCA cycle enzymes of skeletal muscle (27-58%) and heart (29%), and liver NADH oxidase (34%) but did not affect any of these parameters in the iron-sufficient animals. In iron-deficient rats training affected neither the blood hemoglobin level nor any measured iron-dependent enzyme pathway of skeletal muscle but substantially increased endurance (230%). We conclude that the training-induced increase in endurance in iron-deficient rats may be related to cardiovascular improvements, elevations in liver oxidative capacity, and increases in the activities of oxidative enzymes that do not contain iron in skeletal and cardiac muscle.     

Exercise training changes autonomic cardiovascular balance in mice.

Experiments were performed to investigate the influence of exercise training on cardiovascular function in mice. Heart rate, arterial pressure, baroreflex sensitivity, and autonomic control of heart rate were measured in conscious, unrestrained male C57/6J sedentary (n = 8) and trained mice (n = 8). The exercise training protocol used a treadmill (1 h/day; 5 days/wk for 4 wk). Baroreflex sensitivity was evaluated by the tachycardic and bradycardic responses induced by sodium nitroprusside and phenylephrine, respectively. Autonomic control of heart rate and intrinsic heart rate were determined by use of methylatropine and propranolol. Resting bradycardia was observed in trained mice compared with sedentary animals [485 +/- 9 vs. 612 +/- 5 beats/min (bpm)], whereas mean arterial pressure was not different between the groups (106 +/- 2 vs. 108 +/- 3 mmHg). Baroreflex-mediated tachycardia was significantly enhanced in the trained group (6.97 +/- 0.97 vs. 1.6 +/- 0.21 bpm/mmHg, trained vs. sedentary), whereas baroreflex-mediated bradycardia was not altered by training. The tachycardia induced by methylatropine was significantly increased in trained animals (139 +/- 12 vs. 40 +/- 9 bpm, trained vs. sedentary), whereas the propranolol effect was significantly reduced in the trained group (49 +/- 11 vs. 97 +/- 11 bpm, trained vs. sedentary). Intrinsic heart rate was similar between groups. In conclusion, dynamic exercise training in mice induced a resting bradycardia and an improvement in baroreflex-mediated tachycardia. These changes are likely related to an increased vagal and decreased sympathetic tone, similar to the exercise response observed in humans.     

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.     

Aging and respiratory muscle metabolic plasticity: effects of endurance training.

We examined the oxidative and antioxidant enzyme activities in respiratory and locomotor muscles in response to endurance training in young and aging rats. Young adult (4-mo-old) and old (24-mo-old) female Fischer 344 rats were divided into four groups: 1) young trained (n = 12), 2) young untrained (n = 12), 3) old trained (n = 10), and 4) old untrained (n = 6). Both young and old endurance-trained animals performed the same training protocol during 10 wk of continuous treadmill exercise (60 min/day, 5 days/wk). Compared with young untrained animals, the young trained group had significantly elevated (P less than 0.05) activities of 3-hydroxyacyl-CoA dehydrogenase (HADH), glutathione peroxidase (GPX), and citrate synthase (CS) in both the costal diaphragm and the plantaris muscle. In contrast, training had no influence (P greater than 0.05) on the activity of lactate dehydrogenase within the costal diaphragm in young animals. In the aging animals, training did not alter (P greater than 0.05) activities of CS, HADH, GPX, or lactate dehydrogenase in the costal diaphragm but significantly (P less than 0.05) increased CS, HADH, and GPX activities in the plantaris muscle. Furthermore, training resulted in higher activities of CS and HADH in the intercostal muscles in the old trained than in the old untrained animals. Finally, activities of CS, HADH, and GPX were significantly (P less than 0.05) lower in the plantaris in the old untrained than in the young untrained animals; however, CS, HADH, and GPX activities were greater (P less than 0.05) in the costal diaphragm in the old sedentary than in the young untrained animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise training reverses downregulation of HSP70 and antioxidant enzymes in porcine skeletal muscle after chronic coronary artery occlusion

Oxidative stress is associated with muscle fatigue and weakness in skeletal muscle of ischemic heart disease patients. Recently, it was found that endurance training elevates protective heat shock proteins (HSPs) and antioxidant enzymes in skeletal muscle in healthy subjects and antioxidant enzymes in heart failure patients. However, it is unknown whether coronary ischemia and mild infarct without heart failure contributes to impairment of stress proteins and whether exercise training reverses those effects. We tested the hypothesis that exercise training would reverse alterations in muscle TNF-alpha, oxidative stress, HSP70, SOD (Mn-SOD, Cu,Zn-SOD), glutathione peroxidase (GPX), and catalase (CAT) due to chronic coronary occlusion of the left circumflex (CCO). Yucatan swine were divided into three groups (n = 6 each): sedentary with CCO (SCO); 12 wk of treadmill exercise training following CCO (ECO); and sham surgery controls (sham). Forelimb muscle mass-to-body mass ratio decreased by 27% with SCO but recovered with ECO. Exercise training reduced muscle TNF-alpha and oxidative stress (4-hydroxynonenal adducts) caused by CCO. HSP70 levels decreased with CCO (-45%), but were higher with exercise training (+348%). Mn-SOD activity, Mn-SOD protein expression, and Cu,Zn-SOD activity levels were higher in ECO than SCO by 72, 82, and 112%, respectively. GPX activity was 177% greater in ECO than in SCO. CAT trended higher (P = 0.059) in ECO compared with SCO. These data indicate that exercise training following onset of coronary artery occlusion results in recovery of critical stress proteins and reduces oxidative stress.     

Effect of antioxidant vitamin treatment on the time course of hematological and hemorheological alterations after an exhausting exercise episode in human subjects.

This study examined the effects of a 2-mo antioxidant vitamin treatment on acute hematological and hemorheological alterations induced by exhausting exercise; both sedentary and trained individuals were employed. Eighteen young male, human subjects (9 sedentary, 9 trained by regular exercise) participated in the study and performed an initial maximal aerobic cycle ergometer exercise with frequent blood sampling over a 24-h period and analysis of hematological and hemorheological parameters. All subjects were treated with an antioxidant vitamin A, C, and E regimen, supplemented orally for 2 mo, and then subjected to a second exercise test and blood sampling at the end of this period. In the sedentary group during the first testing period (before vitamin treatment), white blood cell counts and granulocyte percentages were increased at 2 h after the exercise test and remained elevated for 4-12 h. Red blood cell (RBC) deformability and aggregation were also altered by exercise in the sedentary group before vitamin treatment. However, none of these parameters in the sedentary group were altered by exercise after the 2-mo period of antioxidant vitamin treatment. With the exception of a transient rise in granulocyte percentage, these parameters were also not affected in the trained subjects before the vitamin treatment. Significant increases of RBC lipid peroxidation observed 12 h after the exercise test in both sedentary and trained subjects were also totally prevented by vitamin treatment. Our results indicate that antioxidant vitamin treatment is effective in preventing the inflammation-like response and coincident adverse hemorheological changes after an episode of exhausting exercise, and suggest that such changes may be related to exercise-induced death events.     

Effect of exercise training on antioxidant enzymes and cardiotoxicity of doxorubicin

The purpose of this study was to correlate the exercise-induced changes of oxidant stress enzymes with possible modification of the response to the putative oxidant stressor doxorubicin. Enzymatic and histological changes were studied in mice placed on a 21-wk swim training program (1 h/day, 5 days/wk) with and without anthracycline administration. Doxorubicin (4 mg/kg) was administered intravenously through a tail vein on 10 separate days over a 7-wk period (twice weekly during weeks 10, 11, 14, 15, and 16). Blood, liver, and heart levels of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GP) were measured following the 9th and 21st wk. Myocardial histomorphological observations were made by light microscopy after 21 wk. Following 9 wk of training swim-trained animals had significantly elevated levels of CAT, SOD, and GP in blood, as well as elevated GP in liver. After 21 wk, trained animals, regardless of drug status, had elevated blood CAT and SOD activity and increased liver CAT and GP. Training also produced increases in blood GP, liver SOD, and heart CAT; however, in conjunction with doxorubicin these changes were not seen. The degree of cardiotoxicity was significantly greater in the sedentary drug-treated animals than in the swim-trained drug-treated animals. The results suggest a correlation between antioxidant enzyme levels in blood and liver and the degree of damage caused by an anthracycline drug. It was concluded that exercise ameliorates severe toxic damage caused by doxorubicin administration, possibly by increasing enzymes that combat free radical damage.     

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.     

Low-intensity exercise training during doxorubicin treatment protects against cardiotoxicity.

Doxorubicin (Dox) is a highly effective antineoplastic antibiotic associated with a dose-limiting cardiotoxicity that may result in irreversible cardiomyopathy and heart failure. The purpose of this study was to examine the effects of low-intensity exercise training (LIET) during the course of Dox treatment on cardiac function, myosin heavy chain expression, oxidative stress, and apoptosis activation following treatment. Male Sprague-Dawley rats either remained sedentary or were exercise trained on a motorized treadmill at 15 m/min, 20 min/day, 5 days/wk (Monday through Friday) for 2 wk. During the same 2-wk period, Dox (2.5 mg/kg) or saline was administered intraperitoneally to sedentary and exercised rats 3 days/wk (Monday, Wednesday, Friday) 1-2 h following the exercise training sessions (cumulative Dox dose: 15 mg/kg). Five days following the final injections, hearts were isolated for determination of left ventricular (LV) function, lipid peroxidation, antioxidant enzyme protein expression, 72-kDa heat shock protein expression, caspase-3 activity, and myosin heavy chain isoform expression. Dox treatment significantly impaired LV function and increased caspase-3 activity in sedentary animals (P < 0.05). LIET attenuated the LV dysfunction and apoptotic signal activation induced by Dox treatment and increased glutathione peroxidase expression, but it had no significant effect on lipid peroxidation, protein expression of myosin heavy chain isoforms, 72-kDa heat shock protein, or superoxide dismutase isoforms. In conclusion, our data suggest that LIET applied during chronic Dox treatment protects against cardiac dysfunction following treatment, possibly by enhancing antioxidant defenses and inhibiting apoptosis.     

Preconditioning with diosgenin and treadmill exercise preserves the cardiac toxicity of isoproterenol in rats

This study was aimed to evaluate the preventive effect of diosgenin and exercise on tissue antioxidant status in isoproterenol-induced myocardial infarction (MI) in male Wistar rats. Levels of lipid peroxides, reduced glutathione (GSH), and the activities of glutathione-dependent antioxidant enzymes (glutathione peroxidise and glutathione reductase) and antiperoxidative enzymes (catalase and superoxide dismutase) in the plasma and the heart tissue of experimental groups of rats were determined. Pretreatment with diosgenin and exercise exerted an antioxidant effect against isoproterenol-induced myocardial infarction by blocking the induction of lipid peroxidation. A tendency to prevent the isoproterenol-induced alterations in the level of GSH, in the activities of glutathione-dependent antioxidant enzymes and antiperoxidative enzymes was also observed. Histopathological findings of the myocardial tissue showed a protective role for combination of diosgenin and exercise in isoproterenol (ISO)-treated rats. Thus, the present study reveals that preconditioning with diosgenin and exercise exerts cardioprotective effect against ISO-induced MI due to its free radical scavenging and antioxidant effects, which maintains the tissue defense system against myocardial damage.     

Response of hepatic antioxidant system to exercise training in aging female rat

This study was undertaken to investigate the effect of exercise training on aging in the hepatic oxidative status and antioxidant defense of female albino rat. Two age groups of 3 months and 12 months old Wistar strain female albino rats were given chronic exercise training for a period of 12 weeks. The antioxidant enzyme assays were carried out by the standard methods. Lower (P<0.01) activities of the antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) by 21%, 44% and 63% respectively was observed in the older rats when compared to younger rats. Also, glutathione (GSH) levels were 42% lower (P<0.01) in older than younger animals. Exercise training to the 12 months aged rats significantly (P<0.01) elevated these antioxidant enzyme activities and GSH content, when compared to older control rats. These levels are almost equal to the values observed in the younger control rats. The levels of lipid peroxidation end product, malondialdehyde (MDA) the major indicator of oxidative stress, was found to increase with age (11%) and exercise training caused further elevation (28% of control). The present findings imply that the reactive oxygen species that are generated due to aging process were detoxified by the exercise induced antioxidant system in the liver tissue. These findings are also in agreement with similar changes in male animals, which clearly envisage no gender difference in the amelioration of the antioxidant enzyme system in older age due to exercise. In conclusion, it can be stated that twelve weeks treadmill exercise training has beneficial effect in improving antioxidant defense capacity by augmenting SOD, CAT and GR activities and GSH levels of older rats, thereby preventing oxidative damage to the liver tissue.     

Lipid peroxidation and scavenger enzymes during exercise: adaptive response to training

This study was designed to determine whether endurance training would influence the production of lipid peroxidation (LI-POX) by-products as indicated by malondialdehyde (MDA) at rest and after an acute exercise run. Additionally, the scavenger enzymes catalase (CAT) and superoxide dismutase (SOD) were examined to determine whether changes in LIPOX are associated with alterations in enzyme activity both at rest and after exercise. Male Sprague-Dawley rats (n = 32) were randomly assigned to either trained or sedentary groups and were killed either at rest or after 20 min of treadmill running. The training program increased oxidative capacity 64% in leg muscle. After exercise, the sedentary group demonstrated increased LIPOX levels in liver and white skeletal muscle, whereas the endurance-trained group did not show increases in LIPOX after exercise. CAT activity was higher in both red and white muscle after exercise in the trained animals. Total SOD activity was unaffected by either acute or chronic exercise. These data suggest that endurance training can result in a reduction in LIPOX levels as indicated by MDA during moderate-intensity exercise. It is possible that activation of the enzyme catalase and the increase in respiratory capacity were contributory factors responsible for regulating LIPOX after training during exercise.     

MRP1/GS‐X pump ATPase expression: is this the explanation for the cytoprotection of the heart against oxidative stress‐induced redox imbalance in comparison to skeletal muscle cells?

Striated muscle activity is always accompanied by oxidative stress (OxStress): the more intense muscle work and/or its duration, the more a redox imbalance may be attained. In spite of cardiac muscle functioning continuously, it is well known that the heart does not suffer from OxStress-induced damage over a broad physiological range. Although the expression of antioxidant enzymes may be of importance in defending heart muscle against OxStress, a series of combined antioxidant therapeutic approaches have proved to be mostly ineffective in avoiding cellular injury. Hence, additional mechanisms may be involved in heart cytoprotection other than antioxidant enzyme activities. The strong cardiotoxic effect of doxorubicin-induced cancer chemotherapy shed light on the possible role for multidrug resistance-associated proteins (MRP) in this context. Muscle activity-induced 'physiological' OxStress enhances the production of glutathione disulfide (GSSG) thus increasing the ratio of GSSG to glutathione (GSH) content inside the cells, which, in turn, leads to redox imbalance. Since MRP1 gene product (a GS-X pump ATPase) is a physiological GSSG transporter, adult Wistar rats were tested for MRP1 expression and activity in the heart and skeletal muscle (gastrocnemius), in as much as the latter is known to be extremely sensitive to muscle activity-induced OxS. MRP1 expression was completely absent in skeletal muscle. In contrast, the heart showed an exercise training-dependent induction of MRP1 protein expression which was further augmented (2.4-fold) as trained rats were challenged with a session of acute exercise. On the other hand, inducible expression of the 70-kDa heat shock protein (HSP70), a universal marker of cellular stress, was completely absent in the heart of sedentary and acutely exercised rats, whereas skeletal muscle showed a conspicuous exercise-dependent HSP70 expression, which decreased by 45% with exercise training. This effect was paralleled by a 58% decrease in GSH content in skeletal muscle which was even higher (an 80%-fall) after training thus leading to a marked redox imbalance ([GSSG]/[GSH] raised up to 38-fold). In the heart, GSH contents and [GSSG]/[GSH] ratio remained virtually unchanged even after exercise challenges, while GS-X pump activity was found to be 20% higher in the heart related to skeletal muscle. These findings suggest that an intrinsic higher capacity to express the MRP1/GS-X pump may dictate the redox status in the heart muscle thus protecting myocardium by preventing GSSG accumulation in cardiomyocytes as compared to skeletal muscle fibres.     

Different effects of exercise tests on the antioxidant enzyme activities in lymphocytes and neutrophils

We have determined the effects of maximal and submaximal cycloergometer tests on the antioxidant enzyme defences of neutrophils and lymphocytes. We also compared the neutrophil and lymphocyte basal enzyme antioxidant activities. A total of 17 well-trained amateur athletes, runners, and cyclists participated in this study. Two tests were performed on an electromagnetic reduction cycloergometer: the maximal exercise test, and the submaximal prolonged exercise test. Blood samples were taken before and after the tests. Basal enzyme activity of superoxide dismutase was higher in lymphocytes but neutrophils presented higher activities of catalase and glutathione peroxidase. The maximal test increased the circulating number of lymphocytes and the activities of catalase and glutathione peroxidase. No changes were observed in lymphocyte number or in lymphocyte antioxidant enzyme activities after the submaximal test. The circulating number of neutrophils increased significantly after the submaximal test. Maximal and submaximal tests decreased the activities of neutrophil glutathione dependent antioxidant enzymes (glutathione peroxidase and glutathione reductase), but no changes were observed in catalase or superoxide dismutase activities after either test. Neither the maximal nor submaximal test produced increases in serum activities of lactate dehydrogenase and creatine kinase (CK).