Role of gamma-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 gamma-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 mumol/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 mumol/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.
Tanaka
T
T
Department of Public Health, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Naganuma
A
A
Imura
N
N
D000818:Animals; D001692:Biological Transport; D005978:Glutathione / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008628:Mercury / Q000493:pharmacokinetics / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D009578:Nitrobenzenes / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000502:physiology*
D007555:Isoxazoles; D009578:Nitrobenzenes; C028328:1,2-dichloro-4-nitrobenzene; D005723:gamma-Glutamyltransferase; D008628:Mercury; D005978:Glutathione; C006303:acivicin