ROLE OF GAMMA-GLUTAMYL-TRANSPEPTIDASE AND BETA-LYASE IN THE NEPHROTOXICITY OF HEXACHLORO-1,3-BUTADIENE AND METHYL MERCURY IN MICE

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 dl-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. © 1990.