The Role Of Xanthine Oxidase In Muscle Oxidative Damage Caused By Repeated Sprinting Exercise

Abstract

Xanthine oxidase (XO) plays an important role in generating reactive oxygen species (ROS) during organ ischemia-reperfusion. Activation of XO has been postulated to underlie the mechanism of tissue oxidative damage resulting from high-intensity muscular contraction. Purpose The purpose of this study was two-fold: (1) to investigate whether high-intensity sprinting exercise would generate ROS and elicit oxidative damage to the heart and skeletal muscle in rats; and (2) to examine whether administration of allopurinol (ALP), a XO inhibitor, would attenuate oxidative tissue damage. Methods Female Sprague-Dawley rats (age 4 mo) were randomly divided into three groups: (1) rested (R, N=9); (2) sprinting on treadmill at 35 m/min, 15% grade, for 3 min followed by 3 min rest, repeated until exhaustion (ST, N=9); and (3) receiving two i.p. injections of ALP (0.4 mmol/kg body wt each) 24 and 1 h prior to ST (ST+ALP, N=9). Heart and three types of skeletal muscle were collected immediately after rats were killed. Results Time of running to exhaustion was not different between ST (86.2 ± 6.6 min) and ST/ALP (89.2 ± 6.3 min). ROS generation measured with the 2',7'-dichlorofluorescein method in fresh homogenate was not different between R, ST and ST/ALP in the heart or skeletal muscle. ST decreased glutathione (GSH) content, increased glutathione disulfide (GSSG) content and lowered the GSH:GSSG ratio in the heart and superficial vastus lateralis (SVL) muscle, whereas ALP attenuated the ST-induced GSH disturbance. Lipid peroxidation measured by malondialdehyde content was increased in ST vs. R, but unchanged in ST/ALP vs. R. Conclusion High-intensity sprinting exercise imposes an oxidative stress to heart and glycolytic muscle fibers, which can be attenuated by ALP treatment. Whether the source of ROS originated from XO requires further investigation.