Acute effects of methylmercury on hepatic and renal glutathione metabolisms in mice.
Because of its high affinity to the sulfhydryl group, the in vivo fate of methylmercury (MeHg) is closely related to the glutathione (GSH) metabolism. Here, to examine the possible effects of MeHg on the GSH metabolism, C57BL female mice were challenged by this heavy metal at a marginal dose level to induce slight renal dysfunction. Liver and blood GSH levels decreased by 16% and 20%, respectively, 24 h after MeHg (160 mumol/kg) administration, whereas kidney and plasma levels drastically increased. The GSH half-lives obtained using L-buthionine-(S,R)-sulfoximine were shortened by 17% in the liver, but lengthened by 28% in the kidney. The accelerated secretion of GSH from the liver and/or blood cells might have caused increased plasma levels of the tripeptide, which in turn could increase the supply of the constituent amino acids for GSH synthesis to the kidney. Furthermore, renal gamma-glutamylcysteine synthetase activity, a rate-determining enzyme in GSH biosynthesis, was found to be enhanced in the MeHg-treated group. The marked increase in the renal GSH levels induced by MeHg could be due to the increased synthesis and the decreased efflux of the tripeptide in this tissue. The MeHg-induced alterations of GSH metabolism described here might reflect one of the defense mechanisms of bioorganisms against the challenge by MeHg.
Yasutake
A
A
Biochemistry Section, National Institute for Minamata Disease, Kumamoto, Japan.
Hirayama
K
K
D000818:Animals; D005260:Female; D005721:Glutamate-Cysteine Ligase / Q000096:biosynthesis; D005978:Glutathione / Q000097:blood / Q000378:metabolism*; D006207:Half-Life; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008767:Methylmercury Compounds / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D013438:Sulfhydryl Compounds / Q000378:metabolism
D008767:Methylmercury Compounds; D013438:Sulfhydryl Compounds; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione