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.