Na+, K(+)-ATPase, glutathione, and hydroxyl free radicals in cadmium chloride-induced testicular toxicity in mice.

Cadmium chloride (CdCl2)-induced biochemical changes were characterized in male, CD-1 mouse testes. CdCl2 inhibited the testes microsomal Na+,K(+)-ATPase activity in vitro and in vivo. The inhibitory range was 30-50 microns and the concentration for half maximal inhibition (IC50 value) was 90 microns over 5 min preincubation. CdCl2 (2mg/kg/day, s.c.) for 2 days significantly inhibited testes Na+,K(+)-ATPase (near 90% inhibition). The content of testicular GSH and the ratio of reduced glutathione (GSH)/GSSG (oxidized glutathione) decreased in CdCl2-treated groups. Using salicylate as a trapping agent and high pressure liquid chromatography with electrochemical detection (LCED), we measured the OH production in vivo. 2,5-dihydroxybenzoic acid (2,5-DHBA) and 2,3-dihydroxybenzoic 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 increase in OH. generation in testes. From this study, it was demonstrated that CdCl2 induced testicular toxicity could possibly be mediated by a significant increase in hydroxyl free radical formation and a reduction in GSH content and Na+,K(+)-ATPase activity. Vitamin E seems to prevent the CdCl2 induced increase in hydroxyl free radical generation.