Glutathione-dependent modulation of exhausting exercise-induced changes in neutrophil function of rats.

Reduced glutathione (GSH) plays a central role in maintaining an effective synergism between various physiological and exogenous antioxidants. We tested the effects of GSH and N-acetylcysteine (NAC, a pro-GSH clinical drug), intraperitoneal (i.p.) supplementation and GSH deficiency on exercise-induced leucocyte margination and neutrophil oxidative burst activity. GSH, NAC (1g.kg-1) or placebo saline was i.p. injected (one or eight times) to male rats (n > or = seven per group). The GSH-deficient rats were prepared by i.p. injections of L-buthionine-[SR]-sulphoximine (BSO, 6 mmol.l-1.kg-1) twice daily for 4 days. Exercised animals were subjected to treadmill run to exhaustion. Exhausting treadmill exercise significantly decreased peripheral blood leucocyte count in the controls (P < 0.001). Such exercise-associated leucocyte margination was prevented by GSH supplementation. Peripheral blood neutrophil counts were significantly higher (P < 0.02) in the GSH-supplemented groups compared to the placebo control groups. Exercise-induced increase in peripheral blood neutrophil oxidative burst activity as measured by luminol-enhanced chemiluminescence per volume of blood tended to be higher in the GSH-supplemented group (P < 0.10), and lower in the GSH-deficient rats (P < 0.02). In these experiments, for the first time we have shown that GSH supplementation can induce neutrophil mobilization and decrease exercise-induced leucocyte margination, and that exogenous and endogenous GSH can regulate exercise-induced stimulation of the neutrophil oxidative burst.