Potential ergogenic effects of l-arginine against oxidative and inflammatory stress induced by acute exercise in aging rats

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Abstract

In this study, we report protective effects of dietary l-arginine (l-Arg) supplementation against oxidative stress and inflammation in aging rats during exhaustive exercise. Thirty 18-month-old male Sprague–Dawley rats were randomly divided into four groups: sedentary control (SC); sedentary control with l-Arg treatment (SC + Arg); exhaustive exercise (E); and exhaustive exercise with l-Arg treatment (E + Arg). Rats in groups SC + Arg and E + Arg received a 2% l-Arg diet. Rats in groups E and E + Arg performed an exhaustive running test on a treadmill. The mean duration of exercise differed significantly between groups E and E + Arg (51 ± 6 versus 63 ± 3 min). Results showed significant increases in xanthine oxidase (XO) and myeloperoxidase (MPO) activities and in lipid peroxidation end-product (malondialdehyde, MDA) levels of myocardial, muscular, hepatic, pulmonary, and renal tissues of exercised rats compared with SC and SC + Arg rats. The increased XO and MPO activities and MDA levels significantly decreased in exercised rats that were fed a diet supplemented with l-Arg. We also found that l-Arg supplementation prevented exhaustive exercise-induced elevations of plasma aminotransferase activity, and lactate and uric acid levels in aging rats. These findings suggest that l-Arg supplementation enhances exercise capacity and protects against oxidative damage and inflammatory responses caused by exhaustive exercise in aging rats.

Introduction

Exhaustive physical exercise has been shown to induce free radicals in vivo and lead to oxidative damage in multiple organs such as muscle, liver, lung, and heart in adult male or female albino rats (Kumar et al., 1992, Frankiewicz-Jozko et al., 1996, Ashton et al., 1998, Radak et al., 1998). In the recent years, there has been much interest in the role of improper activation or up-regulation of xanthine oxidase (XO) or myeloperoxidase (MPO) in the pathogenesis of inflammatory disorders, including strenuous exercise-induced damage of different tissues (Gomez-Cabrera et al., 2005, Morozov et al., 2006). XO, a metalloflavoprotein, plays a major role for oxygen-derived free radicals in post-ischemic tissue injury (McCord, 1985). It was found that XO increased significantly in the circulation and tissues during exhaustive exercise (Radak et al., 1995, Hellsten et al., 1997, Vina et al., 2000). Vina et al. (2000) further demonstrated that XO is responsible for free radical production and tissue damage during exhaustive exercise. In a previous study, Judge and his colleague proposed that XO-derived oxidants are chemotactic to neutrophils (Judge and Dodd, 2004), and that neutrophils infiltration into tissues is associated with strenuous exercise-induced tissue damage in human and animal studies (Fielding et al., 1993, Belcastro et al., 1996, Tiidus, 1998). MPO is released by activated neutrophils and its activity is used as a marker for neutrophils infiltration into tissues. These studies indicate that both of XO and MPO are the two main sources of extracellular free radicals released during strenuous exercise and are responsible for exhaustive exercise-induced oxidative stress in several tissues including heart, skeletal muscle, liver, lung, and kidney.

Recently, there has also been much interest in the role that reactive oxygen species (ROS) play in the pathogenesis of aging (Siomek et al., 2007, Barja, 2007). It has been found that the aged population is more susceptible to oxidative stress induced by many different physiologic situations, such as strenuous exercise (Ji, 2001, Reid and Durham, 2002, Jolitha et al., 2006). Our previous studies have shown that a diet supplemented with l-arginine (l-Arg) significantly attenuated pulmonary and cardiac oxidative stress during exhaustive exercise in young SD rats (Lin et al., 2005, Lin et al., 2006). Therefore, we hypothesized that l-Arg supplementation might also reduce the level of exhaustive exercise-induced tissue damage in aging rats. In this research, we examine whether l-Arg supplementation could reverse the combined inflammatory and oxidative damage that occur in cardiac, muscular, hepatic, pulmonary and renal tissues due to exhaustive exercise in aging rats.

Section snippets

Animals and treatment

Thirty 18-month-old male Sprague–Dawley rats weighing 550–600 g were purchased from the National Laboratory Animal Breeding and Research Center (Taipei, Taiwan). All rats were given free access to water and standard pelleted rat food (No. 5001; PMI Nutrition International, Brentwood, MO, USA) and were individually housed in a room maintained at 23 ± 2 °C and a 12 h light–dark cycle during the first week. This experiment was approved by the Fu-Jen Catholic University Animal Care and Usage Committee

Results

At the end of 30 days, the mean body weights of rats in each group were as follows: SC, 559 ± 36 g; SC + Arg, 592 ± 15 g; E, 596 ± 13 g; and E + Arg, 578 ± 16 g. There were no significant differences in body weight between the four groups. The mean endurance time of the l-arginine-treated group increased by 24% compared with that of the control group (63 ± 3 versus 51 ± 6 min; P < 0.05).

The elevations of cytosolic enzymes in plasma, such as AST, ALT, and LDH were characteristic responses to strenuous exercise and are

Discussion

Laboratory rats are commonly used to investigate the effects of aging and exhaustive exercise on biochemical changes in humans. Our study examined the effects of l-Arg on exhaustive exercise-induced multi-organ oxidative injury in an aging rat model.

Acknowledgement

This study was supported by the National Science Council of Taiwan (NSC 96-2413-H-029-003 to W.-T.L.), and a Grant (SKH-FJU-92-13) from the Shin Kong Wu Ho-Su Memorial Hospital, Taiwan, ROC.

References (51)

  • W.W. Westerfeld et al.

    Further studies with xanthine oxidase inhibitors

    J. Biol. Chem.

    (1959)
  • T. Ashton et al.

    Electron spin resonance spectroscopic detection of oxygen-centred radicals in human serum following exhaustive exercise

    Eur. J. Appl. Physiol. Occup. Physiol.

    (1998)
  • G. Barja

    Mitochondrial oxygen consumption and reactive oxygen species production are independently modulated: implications for aging studies

    Rejuvenation Res.

    (2007)
  • J. Bejma et al.

    Free radical generation and oxidative stress with ageing and exercise: differential effects in the myocardium and liver

    Acta Physiol. Scand.

    (2000)
  • A.N. Belcastro et al.

    Heart, liver, and skeletal muscle myeloperoxidase activity during exercise

    J. Appl. Physiol.

    (1996)
  • G.A. Brooks et al.

    Determination of metabolic and heart rate responses of rats to treadmill exercise

    J. Appl. Physiol.

    (1978)
  • L. Cuzzolin et al.

    Influence of an acute exercise on neutrophil and platelet adhesion, nitric oxide plasma metabolites in inactive and active subjects

    Int. J. Sports Med.

    (2000)
  • S.L. de Oliveira et al.

    Carbohydrate-energy restriction may protect the rat brain against oxidative damage and improve physical performance

    Br. J. Nutr.

    (2003)
  • R.A. Fielding et al.

    Acute phase response in exercise. III. Neutrophil and IL-1 beta accumulation in skeletal muscle

    Am. J. Physiol. Regul. Integr. Comp. Physiol.

    (1993)
  • A. Frankiewicz-Jozko et al.

    Changes in concentrations of tissue free radical marker and serum creatine kinase during the post-exercise period in rats

    Eur. J. Appl. Physiol.

    (1996)
  • M. Fukahori et al.

    Nitric oxide reversibly suppresses xanthine oxidase activity

    Free Radic. Res.

    (1994)
  • M.C. Gomez-Cabrera et al.

    Decreasing xanthine oxidase-mediated oxidative stress prevents useful cellular adaptations to exercise in rats

    J. Physiol.

    (2005)
  • P.M. Hassoun et al.

    Effect of nitric oxide and cell redox status on the regulation of endothelial cell xanthine dehydrogenase

    Am. J. Physiol. Lung Cell Mol. Physiol.

    (1995)
  • Y. Hellsten et al.

    Xanthine oxidase in human skeletal muscle following eccentric exercise: a role in inflammation

    J. Physiol.

    (1997)
  • L.L. Ji

    Exercise at old age: does it increase or alleviate oxidative stress?

    Ann. NY Acad. Sci.

    (2001)
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