Phenobarbital pretreatment protects against morphologic changes in rat bronchiolar epithelium caused by an impurity of malathion.
Oral administration (20 mg/kg) of O,O,S-trimethyl phosphorothioate (OOS) causes delayed toxicity in rats; ie, death occurs as late as 28 days after treatment. OOS-treated rats show morphologic changes in the bronchiolar epithelium of the lung; nonciliated (Clara) cells are fewer but larger 3 days after treatment. We have now found that pretreatment with the P-450-dependent mixed-function oxidase inducer, phenobarbital, protects against the morphologic changes caused by OOS. These results support the view that the lung is a target organ of the delayed toxicity caused by OOS and that OOS detoxification is mediated by P-450-dependent metabolism.
D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000648:ultrastructure; D004848:Epithelium / Q000187:drug effects*; D008658:Inactivation, Metabolic; D008297:Male; D008855:Microscopy, Electron, Scanning; D063086:Organothiophosphates / Q000378:metabolism / Q000633:toxicity*; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D063086:Organothiophosphates; D009946:Organothiophosphorus Compounds; C019123:O,O,S-trimethyl phosphorothioate; D010634:Phenobarbital