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J Toxicol Sci. 2018;43(4):275-280. doi: 10.2131/jts.43.275.

Glutathione has a more important role than metallothionein-I/II against inorganic mercury-induced acute renal toxicity.

Author information

1
Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University.
2
Laboratory of Pathology, Department of Medical Technology, School of Life and Environmental Science, Azabu University.
3
Faculty of Medicine, University of Tsukuba.
4
National Institute for Environmental Studies.
5
Program of Environmental Toxicology, School of Public Health, China Medical University.

Abstract

Inorganic mercury is a harmful heavy metal that causes severe kidney damage. Glutathione (GSH), a tripeptide comprising L-glutamic acid, glycine and L-cysteine, and metallothionein (MT), a cysteine-rich and metal-binding protein, are biologically important protective factors for renal toxicity by inorganic mercury. However, the relationship between GSH and MT for the prevention of renal toxicity by inorganic mercury is unknown. We examined the sensitivity of the mice depleted in GSH by treatment with L-Buthionine-SR-sulfoximine (L-BSO), and MT-I/II null mice genetically deleted for MT-I and MT-II, to inorganic mercury (HgCl2). Kidney damage was not induced in the wild-type mice treated with HgCl2 (30 µmol/kg). In the MT-I/II null mice, renal toxicity was induced by HgCl2 at a dose of 30 µmol/kg but not 1.0 µmol/kg. All GSH-depleted mice of both strains were dead following the injection of HgCl2 (30 µmol/kg). GSH-depleted wild-type mice treated with HgCl2 (1.0 µmol/kg) developed kidney damage similar to MT-I/II null mice treated with HgCl2 (30 µmol/kg). Moreover, renal toxicity induced by HgCl2 (1.0 µmol/kg) was more severe in GSH-depleted MT-I/II null mice compared with GSH-depleted wild-type mice. The present study found that GSH and MT-I/II play cooperatively an important role in the detoxification of severe kidney damage caused by inorganic mercury. In addition, GSH may act as a primary protective factor against inorganic mercury-induced acute renal toxicity, because GSH-depleted mice were more sensitive to inorganic mercury than MT-I/II null mice.

KEYWORDS:

Glutathione; Inorganic mercury; Metallothionein; Nephrotoxicity

PMID:
29618716
DOI:
10.2131/jts.43.275
[Indexed for MEDLINE]
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