Role of gamma-glutamyltranspeptidase 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 gamma-glutamyltranspeptidase (gamma-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 beta-lyase inhibitors, amino-oxyacetic acid (AOAA, 3 x 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 gamma-GT and beta-lyase in the mouse renal toxicity of HCBD and implicate gamma-GT but not beta-lyase in MeHg-induced nephrotoxicity in mice.
Institut National de Recherche et de Sécurité, Vandoeuvre, France.
J
J
de Ceaurriz
M
M
Ban
D058186:Acute Kidney Injury / Q000139:chemically induced*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000480:Alkynes; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D002070:Butadienes / Q000633:toxicity*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced* / Q000201:enzymology / Q000517:prevention & control; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000201:enzymology; D008190:Lyases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D010293:Pargyline / Q000031:analogs & derivatives / Q000494:pharmacology; D013194:Staining and Labeling; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000480:Alkynes; D002070:Butadienes; D007555:Isoxazoles; D008767:Methylmercury Compounds; D000625:Aminooxyacetic Acid; C009055:propargylglycine; D010293:Pargyline; C001335:hexachlorobutadiene; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase; D008190:Lyases; C006303:acivicin; D005998:Glycine