Effect of phenobarbitol pretreatment on regeneration of plasma cholinesterase activity inhibited by parathion or dichlorovos.
Rats were pretreated with phenobarbitol [PB (75 mg/kg, IP)] for 3 days and subsequently injected with parathion, an organophosphorous insecticide, which requires microsomal activation for its anticholinesterase effect or with dichlorovos, a cholinesterase (ChE) inhibitor as such. The difference in the mortality and spontaneous regeneration of inhibited plasma ChE by IP administration of the two insecticides was compared. A single dose of 10 mg/kg parathion caused 100% mortality in PB-untreated rats, but effected no mortality in PB-pretreated rats. A lower dose (7.5 mg/kg) of parathion resulted in plasma ChE levels which were 5, 5, 17, and 93% of initial values in PB-untreated rats and 85, 97, and 92% of initial values in PB-pretreated rats at 2-hr, 1-3-, and 5-day periods, respectively. Mortality resulting from single dose of 30 mg/kg dichlorovos was 30% in PB-pretreated, as well as untreated rats. A lower dose of dichlorovs (20 mg/kg) resulted in plasma ChE activity which was 48, 82, 90, and 97% of initial levels in PB-untreated rats, and 60, 100, 100, and 130% in PB-pretreated rats at 2 hr, 1, 3, and 5 day's, respectively. Administration of 2 mg/kg parathion for 3 days did not affect cytochrome P-450 levels in liver microsomes, but administration of 6 mg/kg dichlorovos for 3 days caused greatly lowered levels of liver microsomal cytochrome P-450, resulting from its inactivation to cytochrome P-420. Phenobarbital caused accelerated in vitro ChE regeneration in the case of dichlorovos-inhibited enzyme in the plasma, but not in the case of parathion-inhibited enzyme.
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D002802:Cholinesterases / Q000097:blood*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004006:Dichlorvos / Q000633:toxicity*; D004347:Drug Interactions; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects; D010278:Parathion / Q000633:toxicity*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats
D002800:Cholinesterase Inhibitors; D010278:Parathion; D004006:Dichlorvos; D003577:Cytochrome P-450 Enzyme System; D002802:Cholinesterases; D010634:Phenobarbital