Effect of metabolic inhibition with piperonyl butoxide on rodent sensitivity to tri-ortho-cresyl phosphate.
The effect of metabolic interference on the onset of organophosphate neuropathy in rats was examined. Long-Evans hooded, male rats were exposed by gavage to single, weekly doses of tri-ortho-cresyl phosphate (TOCP) (1160 mg/kg). Others were pretreated with 50 mg/kg of the mixed-function oxidase inhibitor, piperonyl butoxide (PiPB), 1 h before administering TOCP. The animals were killed after three treatments and their spinal cords, various peripheral nerves, and livers were examined microscopically. Rats treated with PiPB in combination with TOCP showed significantly more damage to both central (spinal cord) and peripheral nervous tissues than those treated with TOCP alone. These data indicate that PiPB can potentiate TOCP-induced neuropathy in rats and suggest that the rodent's resistance to organophosphate neuropathy may have a hepatic basis.
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D003408:Cresols / Q000633:toxicity*; D004195:Disease Models, Animal; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D010525:Peripheral Nerves / Q000187:drug effects*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D010882:Piperonyl Butoxide / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000187:drug effects*; D013118:Spinal Cord Diseases / Q000139:chemically induced; D014317:Tritolyl Phosphates / Q000378:metabolism / Q000633:toxicity*
D003408:Cresols; D014317:Tritolyl Phosphates; D010882:Piperonyl Butoxide; C025541:tri-o-cresyl phosphate