title: Nephrotoxicity of thioformamide, a proximate toxicant of nephrotoxic thiazoles, in mice depleted of glutathione.
abstract: Administration of thioformamide (TFA) (> 2 mmol/kg, sc) in combination with DL-buthionine sulfoximine (BSO) (4 mmol/kg, i.p.), an inhibitor of glutathione (GSH) synthesis, caused kidney injury in male mice. The injury was characterized by tubular necrosis, increases in relative kidney weight and serum urea nitrogen concentration, and a decrease in renal GSH concentration. In contrast to results in male mice, no overt nephrotoxic effects were observed in female mice given TFA in combination with BSO. These features of nephrotoxicity were very similar to those reported for thiabendazole and other nephrotoxic thiazoles in mice depleted of GSH by treatment with BSO; this resemblance supports the suggestion that TFA as a ring cleavage metabolite, or a further metabolite thereof, is responsible for the toxicity of the nephrotoxic thiazoles (Mizutani, T., Yoshida, K., and Kawazoe, S. (1993) Chem. Res. Toxicol. 6, 174-179).
authors.affiliation: Department of Food Science and Nutrition, Kyoto Prefectural University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mizutani
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Murakami
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.forename: K
authors.initials: K
authors.lastname: Nakanishi
mesh_terms: D000818:Animals; D019328:Buthionine Sulfoximine / Q000633:toxicity; D065607:Cytochrome P-450 Enzyme Inhibitors; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005559:Formamides / Q000633:toxicity*; D005978:Glutathione / Q000172:deficiency* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012737:Sex Factors
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D005559:Formamides; D019328:Buthionine Sulfoximine; C009463:thioformamide; D005978:Glutathione