GLUTATHIONE DEPLETION IN RESTED AND EXERCISED MICE - BIOCHEMICAL CONSEQUENCE AND ADAPTATION

The effect of chronic in vivo glutathione (GSH) depletion by L-buthion ine- [S,R]-sulfoximine (BSO) on intracellular and interorgan GSH regul ation was investigated in mice both at rest and after an acute bout of exhaustive swim exercise, BSO treatment for 12 days decreased concent rations of GSH in the liver, kidney, quadriceps muscle, and plasma to 28, 15, 7, and 35%, respectively, compared to GSH-adequate mice. In mo st tissues, with the exception of the kidney, this decrease was associ ated with a concomitant decrease of glutathione disulfide (GSSG) such that the GSH/GSSG ratio was maintained. GSH depletion caused adaptive changes in several enzymes related to GSH regulation, such as liver gl utathione peroxidase (-25%), kidney gamma-glutamyltranspeptidase (+20% ), glutathione disulfide reductase (+131%) and glutathione sulfur-tran sferase ($53%), There was an apparent down-regulation of muscle gamma- glutamyltranspeptidase (-56%) in the GSH-depleted mice, which contribu ted to a conservation of plasma GSH. Exhaustive exercise in the GSH-ad equate state severely depleted GSH content in the liver (-55%) and kid ney (-35%), whereas plasma and muscle GSH levels remained constant, Ho wever, exercise in the GSH-depleted state exacerbated GSH deficit in t he liver (-57%), kidney (-33%), plasma (-65%), and muscle (-25%) in th e absence of adequate reserves of liver GSH. Hepatic lipid peroxidatio n increased by 220 and 290%, respectively, after exhaustive exercise i n the GSH-adequate and -depleted mice. We conclude that GSH homeostasi s is essential for the prooxidant-antioxidant balance during prolonged physical exercise. (C) 1995 Academic Press, Inc.