Increased biliary excretion of cadmium and glutathione by ethanol intake in female rats

Biliary cadmium (Cd) excretion associated with reduced glutathione (GSH) following treatments of cadmium chloride (CdCl2) to female rats fed a 20% ethanol solution for six days was investigated and compared with Cd excretion in male rats. Cadmium chloride injection alone in female rats caused a 3.9-fold increase in cumulative GSH in bile up to 12 h after treatment compared to control female rats. Cadmium chloride injection of ethanol-fed rats caused a 5.0-fold increase in biliary GSH compared to controls. A similar pattern was observed in the biliary concentration of Cd. At 12 h after CdCl2 treatment, the cumulative content of Cd in bile for the CdCl2 and ethanol group was 7.9% of the administered dose. This was almost twice that seen in the CdCl2 alone group (4.2%). The majority of biliary excretion of both GSH and Cd were excreted into bile within 6 h after CdCl2 injection. The enhancement of Cd excretion into bile presented by combination treatment with CdCl2 and ethanol in female rats was higher than in the male rats; however, the enhancement ratio of biliary excretion of Cd by CdCl2 and ethanol treatment in female rats was similar to that for male rats. The levels of both GSH and Cd excretion into bile in female rats were reduced significantly after diethyl maleate (DEM) pretreatment. Diethyl maleate is the hepatic GSH depletion agent. In addition, the effects on the biliary GSH and Cd concentration of simultaneous treatment with ethanol and CdCl2 were not seen with the DEM pretreatment. Sex-related differences in biliary Cd concentration in rats treated with CdCl2 alone vs CdCl2 with ethanol also disappeared following the DEM pretreatment.