Role of glutathione metabolism in heavy metal poisoning

Abstract

Effect of manipulation of GSH status on the in vivo fate of methylmercury (MeHg) was studied. Administration of butyl hydroxyanisole (BHA) (1 g/kg/day for 5 days) to C57BL female mice increased the glutathione (GSH) levels of liver, kidney, blood and plasma and accelerated the hepato-renal efflux of GSH. BHA also increased Hg levels significantly in urine and feces after oral administration of MeHgCl (5 mg/kg).

Male and female mice fed 7.5% protein diet (low protein diet) had lower hepatic GSH levels than animals fed 24% protein diet (normal protein diet). Urinary Hg excretion after oral administration of MeHgCl (5 mg/kg) markedly decreased in animals fed low protein diet (LPD). After 24 h of MeHgCl administration, animals were intraperitoneally injected with glutathione isopropylester (GSE); GSE restored urinary Hg excretion in mice fed LPD toward that in mice fed normal protein diet. These and other results suggest that glutathione status in liver and kidney might be the major factor for determining the rate of elimination of MeHg from a rodent.