Time course of inhibition of acetylcholinesterase and aliesterases following parathion and paraoxon exposures in rats.
The inhibition of cerebral cortex and medulla oblongata acetylcholinesterase and hepatic and plasma aliesterases was studied in female rats following intraperitoneal administration of the phosphorothionate insecticide parathion or its active metabolite paraoxon. Acetylcholinesterase is the target enzyme for organophosphate toxicity while aliesterases are alternative targets for organophosphate inhibition which could serve in a protective capacity during organophosphate intoxication. The effects of pretreatment with cytochrome P450 inducers and inhibitors were also investigated. Pretreatment with phenobarbital slowed the time course of acetylcholinesterase and hepatic aliesterase inhibition following parathion exposure, suggesting the induction of a detoxication pathway(s) to a greater extent than the induction of activation. Although pretreatment with piperonyl butoxide did not affect the rate of acetylcholinesterase inhibition, it slowed hepatic and plasma aliesterase inhibition following parathion administration, presumably from inhibition of the parathion activation pathway. In rats pretreated with beta-naphthoflavone (BNF), hepatic aliesterases demonstrated lower specific activity; additionally, there was a reduced level of inhibition in BNF-pretreated rats following either parathion or paraoxon administration. However, any effects of BNF on parathion- or paraoxon-induced inhibition cannot be distinguished at this time from the effects of the oil vehicle, which reduced esterase inhibition, presumably by its ability to sequester the organophosphate. Brain acetylcholinesterase was partially inhibited before the hepatic aliesterases were maximally inhibited in all treatment groups. In most cases, plasma aliesterases were maximally inhibited within 15 min after organophosphate administration. Thus hepatic aliesterases constitute an important but not completely effective form of protection from the inhibitory effects of organophosphates.
Chambers
J E
JE
Department of Biological Sciences, Mississippi State University, Mississippi 39762.
Chambers
H W
HW
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D001921:Brain / Q000201:enzymology; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors* / Q000097:blood; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004781:Environmental Exposure; D004790:Enzyme Induction; D005260:Female; D008099:Liver / Q000201:enzymology; D010261:Paraoxon / Q000633:toxicity*; D010278:Parathion / Q000633:toxicity*; D010634:Phenobarbital / Q000494:pharmacology; D010882:Piperonyl Butoxide / Q000494:pharmacology; D011041:Poisoning / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D002800:Cholinesterase Inhibitors; D019324:beta-Naphthoflavone; D010278:Parathion; D003577:Cytochrome P-450 Enzyme System; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; D010882:Piperonyl Butoxide; D010261:Paraoxon; D010634:Phenobarbital