NA-ATPASE, GLUTATHIONE, AND HYDROXYL FREE-RADICALS IN CADMIUM CHLORIDE-INDUCED TESTICULAR TOXICITY IN MICE(, K+)

Cadmium chloride (CdCl2)-induced biochemical changes were characterize d in male, CD-1 mouse testes. CdCl2 inhibited the testes microsomal Na +, K+-ATPase activity in vitro and in vivo. The inhibitory range was 3 0-50 mu m and the concentration for half maximal inhibition (IC50 valu e) was 90 mu m over 5 min preincubation. CdCl2 (2mg/kg/day, s.c.) for 2 days significantly inhibited testes Naf,Kf-ATPase (near 90% inhibiti on). The content of testicular GSH and the ratio of reduced glutathion e (GSH)/GSSG (oxidized glutathione) decreased in CdCl2-treated groups. Using salicylate as a trapping agent and high pressure liquid chromat ography with electrochemical detection (LCED), we measured the OH prod uction in vivo. 2,5-dihydroxybenzoic acid (2,5-DHBA) and 2,3-dihydroxy benzoic acid (2,3-DHBA) as indices of hydroxyl free radical formation significantly increased after 5 days CdCl2 exposure. Pretreatment with vitamin E (20 mg/kg, s.i.d., i.m., 7d) protected CdCl2-induced increa se in OH generation in testes. From this study, it was demonstrated th at CdCl2 induced testicular toxicity could possibly be mediated by a s ignificant increase in hydroxyl free radical formation and a reduction in GSH content and Na+, K+-ATPase activity. Vitamin E seems to preven t the CdCl2 induced increase in hydroxyl free radical generation.