Acute exercise increases expression of extracellular superoxide dismutase in skeletal muscle and the aorta

Abstract

Exercise dramatically increases oxygen consumption and causes oxidative stress. Superoxide dismutase (SOD) is important in the first-line defence mechanisms against oxidative stress. To investigate the effect of acute exercise on the expression of SOD, we examined the expression of mRNA for three SOD isozymes, in mice run on a treadmill to exhaustion. Six hours after exercise, the expression of extracellular SOD (EC-SOD) mRNA increased significantly in skeletal muscle and persisted for 24 h, whereas no change was observed for cytoplasmic and mitochondrial SOD mRNA. Moreover, acute exercise also induced EC-SOD mRNA in the aorta. These results suggest that a single bout of exercise is enough to augment the expression EC-SOD mRNA in skeletal muscle and the aorta, and may partly explain the beneficial effect of exercise.     

Skeletal muscle reperfusion injury is enhanced in extracellular superoxide dismutase knockout mouse

This study investigates the role of extracellular SOD (EC-SOD), the major extracellular antioxidant enzyme, in skeletal muscle ischemia and reperfusion (I/R) injury. Pedicled cremaster muscle flaps from homozygous EC-SOD knockout (EC-SOD-/-) and wild-type (WT) mice were subjected to 4.5-h ischemia and 90-min reperfusion followed by functional and molecular analyses. Our results revealed that EC-SOD-/- mice showed significantly profound I/R injury compared with WT littermates. In particular, there was a delayed and incomplete recovery of arterial spasm and blood flow during reperfusion, and more severe acute inflammatory reaction and muscle damage were noted in EC-SOD-/- mice. After 90-min reperfusion, intracellular SOD [copper- and zinc-containing SOD (CuZn-SOD) and manganese-containing (Mn-SOD)] mRNA levels decreased similarly in both groups. EC-SOD mRNA levels increased in WT mice, whereas EC-SOD mRNA was undetectable, as expected, in EC-SOD-/- mice. In both groups of animals, CuZn-SOD protein levels decreased and Mn-SOD protein levels remained unchanged. EC-SOD protein levels decreased in WT mice. Histological analysis showed diffuse edema and inflammation around muscle fibers, which was more pronounced in EC-SOD-/- mice. In conclusion, our data suggest that EC-SOD plays an important role in the protection from skeletal muscle I/R injury caused by excessive generation of reactive oxygen species.     

Tissue distribution of immunoreactive mouse extracellular superoxide dismutase

Protein content and mRNA expression ofextracellular superoxide dismutase (EC-SOD) were investigated in 16 mouse tissues. We developed a double-antibody sandwich ELISA using theaffinity-purified IgG against native mouse EC-SOD. EC-SOD could bedetected in all of the tissues examined (lung, kidney, testis, brownfat, liver, adrenal gland, pancreas, colon, white fat, thymus, stomach,spleen, heart, skeletal muscle, ileum, and brain, in decreasing order of content measured as µg/g wet tissue). Lung showed a markedly higher value of EC-SOD than other tissues. Interestingly, white fat hada high content of EC-SOD in terms of micrograms per milligram protein,which corresponded to that of lung. Kidney showed the strongestexpression of EC-SOD mRNA. Relatively strong expression of the mRNA wasobserved in lung, white fat, adrenal gland, brown fat, and testis.Heart and brain showed only weak signals, and no such expression couldbe detected in either digestive organs or skeletal muscle.Immunohistochemically, EC-SOD was localized mainly to connectivetissues and vascular walls in the tissues examined. Deep staining inthe cytosol was observed in the cortical tubular cells of kidney. Theseresults suggest that EC-SOD is distributed systemically inmice and that the physiological importance of this enzyme may be acompensatory adaptation to oxidative stress, particularly in lung andkidney.

     

Effects of swimming training on three superoxide dismutase isoenzymes in mouse tissues.

The purpose of the present study was to investigate the effects of swimming training on the changes in three superoxide dismutase (SOD) isoenzymes in mice. The trained mice underwent a 6-wk swimming program (1 h/day, 5 days/wk) in water at 35-36 degrees C. Immunoreactive extracellular SOD (EC-SOD), copper- and zinc-containing SOD (CuZn-SOD), and manganese-containing SOD (Mn-SOD) contents and their mRNA abundance were determined in serum, heart, lung, liver, kidney, and gastrocnemius muscle. EC-SOD content in liver and kidney was significantly increased with training. After training, CuZn-SOD content rose significantly only in kidney but decreased significantly in heart, lung, and liver. Mn-SOD content showed a significant increase in lung, kidney, and skeletal muscle but a significant decrease in liver. In most tissues, however, the changes in SOD isoenzyme contents were not concomitant with those in their mRNA levels. The results obtained thus suggest that, except for kidney, the responses in mouse tissues of three SOD isoenzymes (protein levels and mRNA abundance) to swimming training are different and that kidney may be one of the most sensitive organs to adapt to oxidative stress during physical training, although the mechanism remains vague.     

Extracellular superoxide dismutase in tissues from obese (ob/ob) mice

We have examined the protein content and gene expression of three superoxide dismutase (SOD) isoenzymes in eight tissues from obese ob/ob mice, particularly placing the focus on extracellular-SOD (EC-SOD) in the white adipose tissue (WAT). Obesity significantly increased EC-SOD level in liver, kidney, testis, gastrocnemius muscle, WAT, brown adipose tissue (BAT), and plasma, but significantly decreased the isoenzyme level in lung. Tumor necrosis factor-alpha and interleukin-1beta contents in WAT were significantly higher in obese mice than in lean control mice. Immunohistochemically, both WAT and BAT from obese mice could be stained deeply with anti-mouse EC-SOD antibody compared with those from lean mice. Each primary culture per se almost time-dependently enhanced EC-SOD production, and overtly expressed its mRNA. The loss of heparin-binding affinity of EC-SOD type C with high affinity for heparin occurred in kidney of obese mice. These results suggest that the physiological importance of this SOD isoenzyme in WAT may be a compensatory adaptation to oxidative stress.     

Effects of Endurance Training on Three Superoxide Dismutase Isoenzymes in Human Plasma

The effects of endurance training and acute exhaustive exercise on plasma levels of three superoxide dismutase (SOD) isoenzymes and the ability of superoxide generation in neutrophils were studied. Eighteen healthy male students, aged 17–22 years, who volunteered for this study, underwent three months of endurance training in swimming or running. Before and after the training course, they performed acute exercise and blood samples were collected before and after this exercise. The endurance training significantly increased maximal oxygen uptake (V˙O₂max) in all subjects. Neither the endurance training nor the acute exercise affected the plasma CuZn-SOD level. Acute exercise after the training, but not before the training, increased both the plasma Mn-SOD and extracellular SOD (EC-SOD) levels by 33.6 and 33.5%, respectively. The training decreased the EC-SOD level at rest by 22.2%. Acute exercise after the training, but not before the training, increased the plasma lipid peroxide level, suggesting higher oxidative stress in trained subjects during exhaustive exercise. The ability of neutrophils to generate superoxide was increased by the acute exercise, but induction of the superoxide was suppressed after training. These results indicate that EC-SOD levels were changed in a different manner from the CuZn-SOD and Mn-SOD: it was decreased by training but was increased by acute exercise, suggesting that endurance training increases the reserve of EC-SOD in tissues. The results also suggest the possibility of plasma EC-SOD assay as a new index of endurance training.     

Extracellular superoxide dismutase in tissues from obese (ob/ob) mice

We have examined the protein content and gene expression of three superoxide dismutase (SOD) isoenzymes in eight tissues from obese ob/ob mice, particularly placing the focus on extracellular-SOD (EC-SOD) in the white adipose tissue (WAT). Obesity significantly increased EC-SOD level in liver, kidney, testis, gastrocnemius muscle, WAT, brown adipose tissue (BAT), and plasma, but significantly decreased the isoenzyme level in lung. Tumor necrosis factor-α and interleukin-1β contents in WAT were significantly higher in obese mice than in lean control mice. Immunohistochemically, both WAT and BAT from obese mice could be stained deeply with anti-mouse EC-SOD antibody compared with those from lean mice. Each primary culture per se almost time-dependently enhanced EC-SOD production, and overtly expressed its mRNA. The loss of heparin-binding affinity of EC-SOD type C with high affinity for heparin occurred in kidney of obese mice. These results suggest that the physiological importance of this SOD isoenzyme in WAT may be a compensatory adaptation to oxidative stress.     

Extracellular Superoxide Dismutase Induced by Dopamine in Cultured Astrocytes

Under some pathological conditions in brain, a large amount of superoxide anion (O₂ ^?) is produced, causing various cellular damages. Among three isozymes of superoxide dismutase (SOD), extracellular (EC)-SOD should play a role to detoxify O₂ ^? in extracellular space; however, a little is known about EC-SOD in brain. Although dopamine (DA) stored in the synaptic vesicle is stable, the excess leaked DA is spontaneously oxidized to yield O₂ ^? and reactive DA quinones, causing damages of dopaminergic neurons. In the present study, we examined the effects of DA on SOD expression in cultured rat cortical astrocytes. By means of RT-PCR, all mRNA of three isozymes of SOD could be detected; however, only EC-SOD was increased by DA exposure for 24 h, dose-dependently. The expression of EC-SOD protein and the cell-surface SOD activity in astrocytes also increased with 100 μM DA exposure. The increase of EC-SOD mRNA by DA was inhibited by a DA transporter inhibitor, GBR12909, whereas it was not changed by DA receptor antagonists, SKF-83566 (D1) and haloperidol (D2). Furthermore, a monoamine oxidase inhibitor, pargyline, and antioxidants, N-acetyl-l-cysteine and glutathione, also did not affect the DA-induced expression of EC-SOD mRNA. On the other hand, an inhibitor of nuclear factor kappaB (NF-κB), ammonium pyrrolidine-1-carbodithioate, suppressed the DA-induced expression of EC-SOD mRNA. These results suggest that DA incorporated into the cells caused the induction of EC-SOD mRNA followed by the enhancements of EC-SOD protein level and the enzyme activity, and that NF-κB activation is involved in the mechanisms of the EC-SOD induction. The regulation of EC-SOD in astrocytes surrounding dopaminergic neurons may contribute to the defensive mechanism against oxidative stress in brain.     

Cobalt chloride decreases EC-SOD expression through intracellular ROS generation and p38-MAPK pathways in COS7 cells

It is known that cells suffer a chronic hypoxic condition during the development of proximal tubulointerstitial disease. However, it is accepted that extracellular-superoxide dismutase (EC-SOD) protects the cells from oxidative stress. The purpose of this study was to elucidate the regulation of EC-SOD expression in cells under hypoxia. The results show that the expressions of EC-SOD mRNA and protein in cobalt chloride (CoCl₂)-treated COS7 cells decreased in a dose- and time-dependent manner, whereas the expressions of other SOD isoforms (Cu/Zn-SOD and Mn-SOD) were not changed. The down-regulation of EC-SOD mRNA was suppressed by pre-treatment with the antioxidant trolox and the p38 mitogen-activated protein kinase (p38-MAPK) inhibitor SB203580. It is concluded that the expression of EC-SOD is decreased through ROS and p38-MAPK signalling cascades and that the down-regulation of EC-SOD leads to a decrease in the resistance to oxidative stress of COS7 cells under hypoxia induced by CoCl₂.     

Exercise protects against doxorubicin-induced markers of autophagy signaling in skeletal muscle

Doxorubicin (DOX) is an effective antitumor agent used in cancer treatment. Unfortunately, DOX is also toxic to skeletal muscle and can result in significant muscle wasting. The cellular mechanism(s) by which DOX induces toxicity in skeletal muscle fibers remains unclear. Nonetheless, DOX-induced toxicity is associated with increased generation of reactive oxygen species, oxidative damage, and activation of the calpain and caspase-3 proteolytic systems within muscle fibers. It is currently unknown if autophagy, a proteolytic system that can be triggered by oxidative stress, is activated in skeletal muscles following DOX treatment. Therefore, we tested the hypothesis that systemic administration of DOX leads to increased expression of autophagy markers in the rat soleus muscle. Our results reveal that DOX administration results in increased muscle mRNA levels and/or protein abundance of several important autophagy proteins, including: Beclin-1, Atg12, Atg7, LC3, LC3II-to-LCI ratio, and cathepsin L. Furthermore, given that endurance exercise increases skeletal muscle antioxidant capacity and protects muscle against DOX-induced oxidative stress, we performed additional experiments to determine whether exercise training before DOX administration would attenuate DOX-induced increases in expression of autophagy genes. Our results clearly show that exercise can protect skeletal muscle from DOX-induced expression of autophagy genes. Collectively, our findings indicate that DOX administration increases the expression of autophagy genes in skeletal muscle, and that exercise can protect skeletal muscle against DOX-induced activation of autophagy.     

Effect of short-term exercise training on angiogenic growth factor gene responses in rats.

We investigated whether 1) 5 days of exercise training would reduce the acute exercise-induced increase in skeletal muscle growth factor gene expression; and 2) reductions in the increase in growth factor gene expression in response to short-term exercise training would be coincident with increases in skeletal muscle oxidative potential. Female Wistar rats were used. Six groups (rest; exercise for 1-5 consecutive days) were used to measure the growth factor response through the early phases of an exercise training program. Vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), and basic fibroblast growth factor (bFGF) mRNA were analyzed from the left gastrocnemius by quantitative Northern blot. Citrate synthase activity was analyzed from the right gastrocnemius. VEGF and TGF-beta1 mRNA increased after each of 5 days of exercise training, whereas exercise on any day did not increase bFGF mRNA. On day 1, the VEGF mRNA response was significantly greater than on days 2-5. However, the reduced increase in VEGF mRNA observed on days 2-5 was not coincident with increases in citrate synthase activity. These findings suggest that, in skeletal muscle, 1) VEGF and TGF-beta1 mRNA are increased through 5 days of exercise training and 2) the reduced exercise-induced increase in VEGF mRNA responses on days 2-5 does not result from increases in oxidative potential.     

Effects of acute exercise, exercise training, and diabetes on the expression of lymphangiogenic growth factors and lymphatic vessels in skeletal muscle

Blood and lymphatic vessels together form the circulatory system, allowing the passage of fluids and molecules within the body. Recently we showed that lymphatic capillaries are also found in the capillary bed of skeletal muscle. Exercise is known to induce angiogenesis in skeletal muscle, but it is not known whether exercise has effects on lymphangiogenesis or lymphangiogenic growth factors. We studied lymphatic vessel density and expression of the main lymphangiogenic growth factors VEGF-C and VEGF-D and their receptor VEGFR-3 in response to acute running exercise and endurance exercise training in the skeletal muscle of healthy and diabetic mice. VEGF-C mRNA expression increased after the acute exercise bout (P < 0.05) in healthy muscles, but there was no change in diabetic muscles. VEGF-C levels were not changed either in healthy or in diabetic muscle after the exercise training. Neither acute exercise nor exercise training had an effect on the mRNA expression of VEGF-D or VEGFR-3 in healthy or diabetic muscles. Lymphatic vessel density was similar in sedentary and trained mice and was >10-fold smaller than blood capillary density. Diabetes increased the mRNA expression of VEGF-D (P < 0.01). Increased immunohistochemical staining of VEGF-D was found in degenerative muscle fibers in the diabetic mice. In conclusion, the results suggest that acute exercise or exercise training does not significantly affect lymphangiogenesis in skeletal muscle. Diabetes increased the expression of VEGF-D in skeletal muscle, and this increase may be related to muscle fiber damage.     

Effect of exercise, training, and glycogen availability on IL-6 receptor expression in human skeletal muscle.

The cytokine interleukin-6 (IL-6) exerts it actions via the IL-6 receptor (IL-6R) in conjunction with the ubiquitously expressed gp130 receptor. IL-6 is tightly regulated in response to exercise, being affected by factors such as exercise intensity and duration, as well as energy availability. Although the IL-6 response to exercise has been extensively studied, little is known about the regulation of the IL-6R response. In the present study, we aimed to investigate the effect of exercise, training, and glycogen availability, factors known to affect IL-6, on the regulation of gene expression of the IL-6R in human skeletal muscle. Human subjects performed either 10 wk of training with an acute exercise bout before and after the training period, or a low-glycogen vs. normal-glycogen acute exercise trial. The IL-6R mRNA response was evaluated in both trials. In response to acute exercise, an increase in IL-6R mRNA levels was observed. Neither training nor intramuscular glycogen levels had an effect on the IL-6R mRNA response to exercise. However, after 10 wk of training, the skeletal muscle expressed a higher mRNA level of IL-6R compared with before training. The present study demonstrated that the IL-6R gene expression levels in skeletal muscle are increased in response to acute exercise, a response that is very well conserved, being affected by neither training status nor intramuscular glycogen levels, as opposed to IL-6. However, after the training period, IL-6R mRNA production was increased in skeletal muscle, suggesting a sensitization of skeletal muscle to IL-6 at rest.     

Antioxidant enzyme systems in rat liver and skeletal muscle. Influences of selenium deficiency, chronic training, and acute exercise

The influences of selenium deficiency (Se-D), chronic training, and an acute bout of exercise on hepatic and skeletal muscle antioxidant enzymes, i.e., superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX), as well as glutathione S-transferase (GST) and tissue lipid peroxidation, were investigated in post-weaning male Sprague-Dawley rats. Se-D per se depleted GPX in both liver and skeletal muscle but had no effect on SOD or catalase activity. One hour of treadmill running (20 m/min, 0% grade and 27 m/min, 15% grade for untrained and trained rats, respectively) significantly elevated hepatic catalase and cytosolic SOD activity; more prominent activations were found in the Se-D or untrained rats, whereas skeletal muscle antioxidant enzymes were little affected. Ten weeks of training (1 h/day, 5 days/week at 27 m/min, 15% grade) increased hepatic mitochondrial SOD by 23% (P less than 0.05) in Se-D rats. Both hepatic mitochondrial and cytosolic GPX were decreased by training whereas GPX was increased twofold in skeletal muscle mitochondria. Se-independent GPX was elevated by training only in the skeletal muscle mitochondria of Se-D rats. Lipid peroxidation (malondialdehyde formation) was increased by an acute bout of exercise in hepatic mitochondria of the untrained rats and in skeletal muscle mitochondria of the Se-D rats. These data indicate that antioxidant enzymes in liver and skeletal muscle are capable of adapting to selenium deficiency and exercise to minimize oxidative injury caused by free radicals.     

Effects of endurance training on three superoxide dismutase isoenzymes in human plasma

The effects of endurance training and acute exhaustive exercise on plasma levels of three superoxidedismutase (SOD) isoenzymes and the ability of superoxide generation in neutrophils were studied. Eighteen healthy male students, aged 17-22 years, who volunteered for this study, underwent three months of endurance training in swimming or running. Before and after the training course, they performed acute exercise and blood samples were collected before and after this exercise. The endurance training significantly increased maximal oxygen uptake (VO2max) in all subjects. Neither the endurance training nor the acute exercise affected the plasma CuZn-SOD level. Acute exercise after the training, but not before the training, increased both the plasma Mn-SOD and extracellular SOD (EC-SOD) levels by 33.6 and 33.5%, respectively. The training decreased the EC-SOD level at rest by 22.2%. Acute exercise after the training, but not before the training, increased the plasma lipid peroxide level, suggesting higher oxidative stress in trained subjects during exhaustive exercise. The ability of neutrophils to generate superoxide was increased by the acute exercise, but induction of the superoxide was suppressed after training. These results indicate that EC-SOD levels were changed in a different manner from the CuZn-SOD and Mn-SOD: it was decreased by training but was increased by acute exercise, suggesting that endurance training increases the reserve of EC-SOD in tissues. The results also suggest the possibility of plasma EC-SOD assay as a new index of endurance training.     

Role of vitamin C and E supplementation on IL-6 in response to training

Vitamin C and E supplementation has been shown to attenuate the acute exercise-induced increase in plasma interleukin-6 (IL-6) concentration. Here, we studied the effect of antioxidant vitamins on the regulation of IL-6 expression in muscle and the circulation in response to acute exercise before and after high-intensity endurance exercise training. Twenty-one young healthy men were allocated into either a vitamin (VT; vitamin C and E, n = 11) or a placebo (PL, n = 10) group. A 1-h acute bicycling exercise trial at 65% of maximal power output was performed before and after 12 wk of progressive endurance exercise training. In response to training, the acute exercise-induced IL-6 response was attenuated in PL (P < 0.02), but not in VT (P = 0.82). However, no clear difference between groups was observed (group × training: P = 0.13). Endurance exercise training also attenuated the acute exercise-induced increase in muscle-IL-6 mRNA in both groups. Oxidative stress, assessed by plasma protein carbonyls concentration, was overall higher in the VT compared with the PL group (group effect: P < 0.005). This was accompanied by a general increase in skeletal muscle mRNA expression of antioxidative enzymes, including catalase, copper-zinc superoxide dismutase, and glutathione peroxidase 1 mRNA expression in the VT group. However, skeletal muscle protein content of catalase, copper-zinc superoxide dismutase, or glutathione peroxidase 1 was not affected by training or supplementation. In conclusion, our results indicate that, although vitamin C and E supplementation may attenuate exercise-induced increases in plasma IL-6 there is no clear additive effect when combined with endurance training.     

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.     

HSP70 and other possible heat shock or oxidative stress proteins are induced in skeletal muscle, heart, and liver during exercise

Exercise causes heat shock (muscle temperatures of up to 45 degrees C, core temperatures of up to 44 degrees C) and oxidative stress (generation of O2- and H2O2), and exercise training promotes mitochondrial biogenesis (2-3-fold increases in muscle mitochondria). The concentrations of at least 15 possible heat shock or oxidative stress proteins (including one with a molecular weight of 70 kDa) were increased, in skeletal muscle, heart, and liver, by exercise. Soleus, plantaris, and extensor digitorum longus (EDL) muscles exhibited differential protein synthetic responses ([3H]leucine incorporation) to heat shock and oxidative stress in vitro but five proteins (particularly a 70 kDa protein and a 106 kDa protein) were common to both stresses. HSP70 mRNA levels were next analyzed by Northern transfer, using a [32P]-labeled HSP70 cDNA probe. HSP70 mRNA levels were increased, in skeletal and cardiac muscle, by exercise and by both heat shock and oxidative stress. Skeletal muscle HSP70 mRNA levels peaked 30-60 min following exercise, and appeared to decline slowly towards control levels by 6 h postexercise. Two distinct HSP70 mRNA species were observed in cardiac muscle; a 2.3 kb mRNA which returned to control levels within 2-3 h postexercise, and a 3.5 kb mRNA species which remained at elevated concentrations for some 6 h postexercise. The induction of HSP70 appears to be a physiological response to the heat shock and oxidative stress of exercise. Exercise hyperthermia may actually cause oxidative stress since we also found that muscle mitochondria undergo progressive uncoupling and increased O2- generation with increasing temperatures.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antioxidant effect of diphenyl diselenide on oxidative stress caused by acute physical exercise in skeletal muscle and lungs of mice

This study was designed to examine if diphenyl diselenide (PhSe)₂, an organoselenium compound, attenuates oxidative stress caused by acute physical exercise in skeletal muscle and lungs of mice. Swiss mice were pre‐treated with (PhSe)₂ (5 mg kg^‐1 day^‐1) for 7 days. At the 7th day, the animals were submitted to acute physical exercise which consisted of continuous swimming for 20 min. The animals were euthanized 1 and 24 h after the exercise test. The levels of thiobarbituric acid reactive species (TBARS), non‐protein thiols (NPSH) and ascorbic acid and the activity of catalase (CAT) were measured in the lungs and skeletal muscle of mice. Glycogen content was determined in the skeletal muscle of mice. Parameters in plasma (urea and creatinine) were determined. The results demonstrated an increase in TBARS levels induced by acute physical exercise in the skeletal muscle and lungs of mice. Animals submitted to exercise showed an increase in non‐enzymatic antioxidant defenses (NPSH and ascorbic acid) in the skeletal muscle. In lungs of mice, activity of CAT was increased. (PhSe)₂ protected against the increase in TBARS levels and ameliorated antioxidant defenses in the skeletal muscle and lungs of mice submitted to physical exercise. These results indicate that acute physical exercise caused a tissue‐specific oxidative stress in the skeletal muscle and lungs of mice. (PhSe)₂ protected against oxidative damage induced by acute physical exercise in mice. Copyright © 2009 John Wiley & Sons, Ltd.