Inhibitory effect of leptophos on carboxylesterase (isocarboxazid amidase) in rat liver.
The organophosphate insecticide, leptophos, inhibited rat liver isocarboxazid amidase (ISOCase) activity to 20% of control at 5.0 mg/kg l h after administration, but at this dose brain cholinesterase (ChE) activity was not affected. The activity of ISOCase decreased to 29 and 0% of control 24 h after treatment with leptophos at doses of 2.5 and 5.0 mg/kg, respectively. With repeated administration of leptophos at a dose of 1 mg/kg for 10 days, ISOCase activity decreased to 34% of control on day 1 and the inhibition increased to 85% on day 10 without inhibition of brain ChE activity. After cessation of three successive daily doses (1 mg/kg/day), the ISOCase activity was gradually restored near to control levels in 8 days. Pretreatment with carboxylesterase inhibitors, triorthocresylphosphate (TOCP) and bis-p-nitrophenylphosphate (BNPP), potentiated the inhibition of brain ChE by leptophos, suggesting that ISOCase might take a role in leptophos detoxification.
D000818:Animals; D001921:Brain / Q000201:enzymology; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors*; D002800:Cholinesterase Inhibitors; D007306:Insecticides / Q000494:pharmacology*; D010773:Leptophos / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D002800:Cholinesterase Inhibitors; D007306:Insecticides; D010773:Leptophos; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase