Effects of probenecid and acivicin on potassium dichromate-induced acute nephrotoxicity in mice.
Male OF1 mice were injected subcutaneously with 80 mg/kg potassium dichromate (K2Cr2O7). Examination of cryostat kidney sections stained for alkaline phosphatase (APP) revealed damage to about 40-70% of the proximal tubules after 8 h. Pretreatment with the organic anionic transport inhibitor probenecid (i.p., 3 x 0.75 mmol/kg) reduced the number of damaged tubules by 60% in mice treated with potassium dichromate. Pretreatment with the gamma-glutamyltranspeptidase (gamma-GT) inactivator acivicin (AT-125, 50 mg/kg p.o., plus 50 mg/kg i.p.) failed to prevent chromate-induced renal toxicity. These results support the conclusion that a probenecid-sensitive transport process, but not a gamma-GT-catalyzed degradation, is involved in the mouse renal toxicity of potassium dichromate.
Institut National de Recherche et de Sécurité, Vandoeuvre, France.
J
J
De Ceaurriz
M
M
Ban
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D007279:Injections, Subcutaneous; D007555:Isoxazoles / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D011192:Potassium Dichromate / Q000037:antagonists & inhibitors / Q000633:toxicity*; D011339:Probenecid / Q000627:therapeutic use*; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors*
D007555:Isoxazoles; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase; C006303:acivicin; D011339:Probenecid; D011192:Potassium Dichromate