Role of γ-glutamyltranspeptidase in renal uptake and toxicity of inorganic mercury in mice

The role of renal glutathione (GSH) metabolism as a mediating factor in the renal uptake and toxicity of inorganic mercury was investigated in mice by preadministering a γ-glutamyltranspeptidase (GGT) inhibitor, acivicin. Pretreatment with acivicin (0.25, 1.0 or 2.5 mmol/kg, i.p.) led to a dose-dependent decrease in renal mercury content and increases in mercury and GSH contents in urine measured 2 h after HgCl₂ injection (18 μmol/kg, i.v.). Acivicin pretreatment also ameliorated the renal and lethal toxicity caused by administration of inorganic mercury. Treatment of the mice with 1,2-dichloro-4-nitrobenzene (DCNB, 2.5 mmol/kg, i.p.), a specific depletor of hepatic GSH, prior to HgCl₂ injection substantially reduced renal Hg content and consequently reduced the renal damage. In addition, coadministration of GSH (36 μmol/kg, i.v.) with HgCl₂ increased the renal Hg content measured 5 min after HgCl₂ injection to 2.6 fold higher than that of mice treated with HgCl₂ alone. These results suggest that renal uptake of inorganic mercury, which is supposedly transported to the kidney as a mercury-GSH complex, is dependent on a reaction catalyzed by GGT on the outer surface of the renal brush border membrane in the same manner as the metabolism of GSH.