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

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Abstract

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.

Introduction

Cells have developed different antioxidant systems and various antioxidant enzymes to defend themselves against free radical attacks. Superoxide dismutase (SOD), the first line of defense against oxygen-derived free radicals, catalyses the dismutation of the superoxide anion into hydrogen peroxide. H2O2 can be transformed into H2O and O2 by catalase (CAT), which is present in peroxisomes of eukaryotic cells (Michiels et al., 1994). Glutathione-dependent antioxidant system consisting of reduced glutathione (GSH) and an array of functionally related enzymes plays a fundamental role in cellular defense against reactive free radicals and other oxidant species (Sen, 1997, Gul et al., 2000). Of these enzymes, glutathione peroxidase (GPx) is a selenoprotein that reduces hydroperoxides as well as H2O2 while oxidizing glutathione. A number of potentially toxic electrophilic xenobiotics (such as certain carcinogens, bromobenzene, chlorobenzene) are conjugated to the nucleophilic glutathione by glutathione S-transferases (GSTs) present in high amounts in cell cytosol. GST can also catalyze reactions reducing peroxides like GPx. Reduction of oxidized glutathione (GSSG) to GSH is mediated by the widely distributed enzyme GSSG reductase (GRD) that uses NADPH as the reductant (Sen, 1997, Gul et al., 2000).

Exhausting (Khanna et al., 1999, Gul et al., 2003, Oztasan et al., 2004) or moderate (Alessio, 1993, Gul et al., 2001) exercise, in rats may increase ROS production exceeding the capacity of antioxidant defences. Oxidative stress is the imbalance of pro- and anti-oxidants in favor of the former. Exercise-induced oxidative stress was also reported in thoroughbred racehorses after a 1000 m race at maximum velocity (White et al., 2001). Increased oxidative stress can be harmful to all cellular macromolecules, such as lipids, proteins and DNA (Halliwell and Gutteridge, 1984). In contrast, beneficial effects of endurance training on antioxidant defense mechanisms in various tissues have been reported by swim (Kanter et al., 1985, Venditti and Di Meo, 1996) and treadmill-trained normal (Sen et al., 1992, Oztasan et al., 2004) and diabetic (Gul et al., 2002) rats, and also in horses (Avellini et al., 1999) and men (Dane et al., in press).

Heart muscle has a high oxygen uptake at resting conditions. Coronary blood flow increases up to fourfold and oxygen uptake from the blood by heart muscle increases further during heavy physical exercise (Wilmore and Costill, 1999, Gul and Hänninen, 2002). Although it is essential for aerobic metabolism, increased oxygen metabolism can sometimes lead to increased oxidative stress in the heart during physical exercise (Frankiewicz-Jozko et al., 1996, Venditti and Di Meo, 1996, Asami et al., 1998, Gul et al., 2003). The primary source of reactive oxygen species in heart is mitochondria. High oxygen flux in the heart mitochondria may favor a higher rate of leakage of free radicals (Ji, 1994). In addition, xanthine oxidase in cytosole contributes to H2O2 production in the heart especially during ischemia–reperfusion injury (Bindoli et al., 1988). Heart is equipped with all the major antioxidant enzymes, i.e. SOD, CAT and GPx, as well as adequate levels of GRD and GST (Ji, 1994). As recently reviewed (Atalay and Sen, 1999), regular physical exercise may beneficially influence cardiac antioxidant defenses and promote overall cardiac function. However, chronic exercise has dual effects: on the one hand, it results in oxidant formation and oxidative stress; on the other hand, perhaps as a consequence, it may also induce antioxidant enzymes to minimize the effects of oxidative stress due to exercise (Sen, 1995, Tiidus, 1998). Decreased lipid peroxidation in heart tissue by an 8-week treadmill training (with a speed of 20 m min 1 with 10° inclination, for 60 min day 1) in Fisher 344 rats (Husain, 2003) and lower levels of lipid peroxidation after ischemia and reperfusion in left ventricles of female Sprague-Dawley rats after a 10-week endurance exercise training (Powers et al., 1998) have been reported. On the other hand, unchanged lipid peroxidation has been reported after 10-week swim training (Venditti and Di Meo, 1996), after 12-week treadmill training (45-min duration at 25 m min 1 with a 0% slope, 5 days a week) in normal Wistar rats (Moran et al., 2004) and after an 8-week treadmill training in diabetic Wistar rats (Gul et al., unpublished results), and mice (Reddy Avula and Fernandes, 1999). Even increased lipid peroxidation in heart tissue in female Sprague-Dawley rats exercised at 1.6 km h 1, 2 h day 1, 5 days week 1 for 8 weeks (Liu et al., 2000) has been reported.

Alterations in the antioxidant enzymes due to endurance training are also not consistent. Increased GPx activity in heart tissue by endurance training has been reported in rats (Lew and Quintanilha, 1991, Reddy Avula and Fernandes, 1999, Ramires and Ji, 2001, Husain, 2003). Sprint training on a treadmill for 6 weeks increased GPx activity in heart of rats (Atalay et al., 1996). However, unchanged heart tissue GPx activity by training was reported in male Wistar (Moran et al., 2004) and Sprague-Dawley (Ji et al., 1992) rats. In contrast, decreased GPx activity in heart tissue in streptozotocin-induced diabetic male Wistar rats by treadmill training for 8 weeks (Gul et al., 2003) has also been reported. The situation is similar for other antioxidant enzymes (Johnson, 2002). Whether endurance training has beneficial effects on antioxidant defense mechanisms and decreases lipid peroxidation in heart is not yet clear. Therefore, the aim of this study was to investigate whether an 8-week treadmill training strengthens antioxidant enzymes and decreases lipid peroxidation in heart in male rats. In addition, the effects of acute exhaustive exercise on oxidative stress in heart tissue in untrained and trained rats were also investigated. As recently reported, an 8-week endurance training resulted in attenuated exercise-induced oxidative stress in erythrocytes (Oztasan et al., 2004), but did not affect the ventricular weights (Oztasan et al., in press) in these rats. The results of this study may have implications in exercising men.

Section snippets

Animals and groups

12-week-old 56 male rats (Rattus norvegicus, Sprague-Dawley strain) fed with standard laboratory chow and water were used. Animal experimentations were approved by the Ethical Committee of the Ataturk University and carried out in an ethically proper way by following the guidelines provided.

Training and acute exhaustive exercise

Male rats were equally divided into trained (TR, TE) and untrained groups (UR, UE) at random. Both groups were further divided into two groups of 14 where the rats were studied at rest (TR and UR) and

Results

Malondialdehyde level in heart tissue was not affected by acute exhaustive exercise in untrained and trained rats (Table 1).

The activities of GPx (Fig. 1) and GRD (Table 1) enzymes in heart tissue decreased by both acute exercise and training. GST and CAT activities in heart tissue were not affected by either acute exercise or endurance training (Table 1). SOD activity was decreased by acute exercise in untrained rats; however, this decrease was not observed in trained rats (Fig. 2). Total

Discussion

In line with our finding, increased endurance time in rats was reported after treadmill training (2 h day 1, 5 days week 1 for 5 weeks, at a speed of 30 m min 1 at the fifth week, 15° uphill) (Terblanche et al., 2001). As recently noted (Oztasan et al., in press), there was no difference between ventricular weights of untrained and trained groups in our study. No change in ventricular or heart mass in rats (Fuller and Nutter, 1981, Crisman et al., 1985, Senturk et al., 2001) and rabbits (Such

Conclusion

Although both acute exhaustive exercise and endurance training decreased some antioxidant enzyme activities, they could not induce oxidative stress in the heart tissue of the rats. The decrease in SOD activity in heart observed in untrained rats due to acute exercise was prevented by endurance training in trained rats, revealing its potential role in myocardial antioxidant defense. Our results suggested that rat heart has sufficient reserve of antioxidant enzyme capacity to cope with oxidative

Acknowledgement

This study has been supported by The Research Foundation of the Ataturk University, Erzurum, Turkey (2001/53). The authors thank Delali Camgoz who took care of the animals.

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