Probenecid-induced protection against acute hexachloro-1,3-butadiene and methyl mercury toxicity to the mouse kidney.
Male Swiss OF1 mice received a single oral dose of either 80 mg/kg hexachloro-1,3-butadiene (HCBD) or 40 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. Treatment with the organic anion transport inhibitor probenecid (i.p., 3 x 0.75 mmol/kg) did not have any renal effect in normal mice but reduced the number of damaged tubules by 80 and 90% in mice treated with HCBD and MeHg respectively. The results support the conclusion that the toxicity of HCBD and MeHg to the mouse kidney is related to a probenecid-sensitive transport process. It cannot be stated from the present investigation whether the inhibition nephrotoxicity data are related to classic organic anion secretion by the kidney.
Ban
M
M
Institut National de Recherche et de Sécurité, Vandoeuvre, France.
de Céaurriz
J
J
D000818:Animals; D002070:Butadienes / Q000037:antagonists & inhibitors*; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D008767:Methylmercury Compounds / Q000037:antagonists & inhibitors*; D051379:Mice; D011339:Probenecid / Q000494:pharmacology*
D002070:Butadienes; D008767:Methylmercury Compounds; C001335:hexachlorobutadiene; D011339:Probenecid