Mechanism of Free Radical Production in Exhaustive Exercise in Humans and Rats; Role of Xanthine Oxidase and Protection by Allopurinol

Exhaustive exercise generates free radicals. However, the source of this oxidative damage remains controversial. The aim of this paper was to study further the mechanism of exercise‐induced production of free radicals. Testing the hypothesis that xanthine oxidase contributes to the production of free radicals during exercise, we found not only that exercise caused an increase in blood xanthine oxidase activity in rats but also that inhibiting xanthine oxidase with allopurinol prevented exercise‐induced oxidation of glutathione in both rats and in humans. Furthermore, inhibiting xanthine oxidase prevented the increases in the plasma activity of cytosolic enzymes (lactate dehydrogenase, aspartate aminotransferase, and creatine kinase) seen after exhaustive exercise. Our results provide evidence that xanthine oxidase is responsible for the free radical production and tissue damage during exhaustive exercise. These findings also suggest that mitochondria play a minor role as a source of free radicals during exhaustive physical exercise.

[1]  S. Papa,et al.  A Possible Role of Slips in Cytochrome C Oxidase in the Antioxygen Defense System of the Cell , 1997, Bioscience reports.

[2]  J A Thompson,et al.  Circulating plasma xanthine oxidase contributes to vascular dysfunction in hypercholesterolemic rabbits. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Y. Hellsten,et al.  Increased expression of xanthine oxidase and insulin-like growth factor I (IGF-I) immunoreactivity in skeletal muscle after strenuous exercise in humans. , 1996, Acta physiologica Scandinavica.

[4]  C. Sen,et al.  Exercise-induced oxidative stress: glutathione supplementation and deficiency. , 1994, Journal of applied physiology.

[5]  J. Duarte,et al.  Endothelium-derived oxidative stress may contribute to exercise-induced muscle damage. , 1993, International journal of sports medicine.

[6]  K. Hirano,et al.  Binding of human xanthine oxidase to sulphated glycosaminoglycans on the endothelial-cell surface. , 1993, The Biochemical journal.

[7]  J. Sastre,et al.  Exhaustive physical exercise causes oxidation of glutathione status in blood: prevention by antioxidant administration. , 1992, The American journal of physiology.

[8]  J. Webster.  Goodman and Gilman's the Pharmacological Basis of Therapeutics, 8th ed , 1992 .

[9]  A. Favier,et al.  High-performance liquid chromatographic separation of malondialdehyde-thiobarbituric acid adduct in biological materials (plasma and human cells) using a commercially available reagent. , 1992, Journal of chromatography.

[10]  Dean P. Jones,et al.  Oxygen dependence of oxidative stress. Rate of NADPH supply for maintaining the GSH pool during hypoxia. , 1990, Biochemical pharmacology.

[11]  J. Beckman,et al.  Conversion of xanthine dehydrogenase to oxidase in ischemic rat intestine: a reevaluation. , 1988, The American journal of physiology.

[12]  H. P. Jones,et al.  Conversion of xanthine dehydrogenase to oxidase in ischemic rat tissues. , 1987, The Journal of clinical investigation.

[13]  M. Jackson.  Muscle damage during exercise: possible role of free radicals and protective effect of vitamin E , 1987, Proceedings of the Nutrition Society.

[14]  A. Quintanilha,et al.  Severe depletion in liver glutathione during physical exercise. , 1986, Biochemical and biophysical research communications.

[15]  A. Quintanilha,et al.  Changes in the glutathione status of plasma, liver and muscle following exhaustive exercise in rats , 1985, FEBS letters.

[16]  J. McCord,et al.  Oxygen-derived free radicals in postischemic tissue injury. , 1985, The New England journal of medicine.

[17]  G. Brooks,et al.  Free radicals and tissue damage produced by exercise. , 1982, Biochemical and biophysical research communications.

[18]  B Chance,et al.  Hydroperoxide metabolism in mammalian organs. , 1979, Physiological reviews.

[19]  H. Krebs,et al.  Maintenance of glutathione content is isolated hepatocyctes. , 1978, The Biochemical journal.

[20]  B Chance,et al.  The cellular production of hydrogen peroxide. , 1972, The Biochemical journal.

[21]  D. Friend,et al.  HIGH-YIELD PREPARATION OF ISOLATED RAT LIVER PARENCHYMAL CELLS , 1969, The Journal of cell biology.

[22]  Y. Hellsten,et al.  Xanthine oxidase in human skeletal muscle following eccentric exercise: a role in inflammation. , 1997, The Journal of physiology.

[23]  J. Sastre,et al.  Determination of oxidized glutathione in blood: high-performance liquid chromatography. , 1994, Methods in enzymology.

[24]  B. Freeman,et al.  A sensitive fluorometric assay for measuring xanthine dehydrogenase and oxidase in tissues. , 1989, Free radical biology & medicine.

[25]  G. Brooks,et al.  Blood glutathione oxidation during human exercise. , 1988, Journal of applied physiology.