Role of γ-glutamyltranspeptidase and β-lyase in the nephrotoxicity of hexachloro-1,3-butadiene and methyl mercury in mice |
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Authors: | J de Ceaurriz M Ban |
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Institution: | Institut National de Recherche et de Sécurité, Vandoeuvre, France |
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Abstract: | Male Swiss OF1 mice received a single oral dose of either 80 mg/kg hexachloro-1,3-butadiene (HCBD) or 80 mg/kg methyl mercury (MeHg). Examination of cryostat kidney sections stained for alkaline phosphatase (APP) revealed damage to about 50% of the proximal tubules after 8 h. Pretreatment with the γ-glutamyltranspeptidase (γ-GT) inactivator AT-125 (Acivin, 50 mg/kg i.p., plus 50 mg/kg p.o., reduced the number of damaged tubules by 59 and 58% in mice treated with HCBD and MeHg, respectively. Pretreatment with the two β-lyase inhibitors, amino-oxyacetic acid (AOAA, 3 × 100 mg/kg p.o.) and
-propargylglycine (PPG, 300 mg/kg i.p. plus 300 mg/kg p.o), reduced HCBD nephrotoxicity by 46 and 59%, respectively, but did not protect against MeHg nephrotoxicity. The results support a role for γ-GT and β-lyase in the mouse renal toxicity of HCBD and implicate γ-GT but not β-lyase in MeHg-induced nephrotoxicity in mice. |
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Keywords: | Hexachloro-1 3-butadiene Methyl mercury Nephrotoxicity γ-Glutamyltranspeptidase β-Lyase (Mice) |
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