In vivo nephrotoxicity induced in mice by chromium(VI). Involvement of glutathione and chromium(V).
The role of glutathione (GSH) and chromium (V) in chromium (VI)-induced nephrotoxicity in mice was investigated at 24 h after K2Cr(VI)2O7 ip injection. Nephrotoxicity was assessed by measurements of relative kidney weight and serum urea nitrogen. Cr(VI) nephrotoxicity was accompanied by decreased renal GSH and glutathione reductase (GSSG-R) levels. Pretreatment with buthionine sulfoximine, an inhibitor of GSH biosynthesis, enhanced Cr(VI)-induced nephrotoxicity, and remarkably diminished kidney GSH and GSSG-R levels. In contrast, pretreatment with glutathione methyl ester, a GSH-supplying agent, prevented Cr(VI) from exerting a harmful effect on mouse kidney and restored kidney GSH level. Administration of a Cr(V) compound, K3Cr(V)O8, induced much higher toxicity in mouse kidney than Cr(VI), but it failed to diminish renal GSH level. Another Cr(V) compound, Cr(V)-GSH complex, and Cr(III) nitrate did not cause a nephrotoxic effect in mice. The mechanism of Cr(VI)-induced nephrotoxicity was explained using GSH and Cr(V).
Hojo
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Y
Department of Food Science and Nutrition, Kyoto Prefectural University, Japan.
Satomi
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Y
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002840:Chromates / Q000009:adverse effects / Q000633:toxicity; D002857:Chromium / Q000009:adverse effects* / Q000633:toxicity; D004578:Electron Spin Resonance Spectroscopy; D005978:Glutathione / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism; D007668:Kidney / Q000033:anatomy & histology / Q000201:enzymology / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction; D010545:Peroxides / Q000009:adverse effects / Q000633:toxicity; D011192:Potassium Dichromate / Q000009:adverse effects / Q000633:toxicity; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014508:Urea / Q000097:blood
D002840:Chromates; D010545:Peroxides; D013438:Sulfhydryl Compounds; D002857:Chromium; C019537:potassium tetraperoxochromate; D014508:Urea; D005980:Glutathione Reductase; D005978:Glutathione; D011192:Potassium Dichromate