title: Inhibition of cholinesterases by DRP and induction of organophosphate-detoxicating enzymes in rats.
abstract: 1. The inhibition of cholinesterase and carboxylesterase activities in the diisopropyl fluorophosphate (DFP) intoxication, and the inducibility of organophosphate (OP) detoxicating enzymes was studied in rats. 2. In phenobarbital (PB)-, but not in beta-naphthoflavone (NF)-pretreated rats, the activities of DFP-inhibited cholinesterases were 70-120% higher than in non-pretreated rats. Also the inhibition of the microsomal and cytosolic carboxylesterase activity in liver was efficiently antagonized by BP, but not by NF. 3. In vitro the microsomes from PB-treated rats detoxicated DFP probably by O-dealkylation, since no fluoride was released from DFP. Glutathione S-transferase did not detoxicate DFP. 4. 7-Pentoxyresorufin O-dealkylase, a specific enzyme of cytochrome P450IIB subfamily, was induced by PB, flumecinol, isosafrole and NF by 167- 61-, 26- and 1.6-fold, respectively. 7-Ethoxyresorufin O-deethylase, a marker enzyme of cytochrome P450IA subfamily, was induced by those agents 5-, 4-, 31- and 94-fold, given in the same order. Glutathione S-transferase, paraoxonase and DFPase activities were increased 0-72% by the tested inducers. 5. The results suggest that the cytochrome P450IIB subfamily, inducible by PB, participates in DFP detoxication by O-dealkylation. Its induction probably causes the protection against the cholinesterase inhibition by OPs.
authors.affiliation: Department of Physiology, University of Kuopio, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Kaliste-Korhonen
authors.forename: R
authors.initials: R
authors.lastname: Törrönen
authors.forename: P
authors.initials: P
authors.lastname: Ylitalo
authors.forename: O
authors.initials: O
authors.lastname: Hänninen
mesh_terms: D000110:Acetylcholinesterase / Q000096:biosynthesis; D000818:Animals; D043303:Aryldialkylphosphatase; D001571:Benzoflavones / Q000494:pharmacology; D002265:Carboxylic Ester Hydrolases / Q000096:biosynthesis; D002800:Cholinesterase Inhibitors; D002802:Cholinesterases / Q000096:biosynthesis; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D004950:Esterases; D005982:Glutathione Transferase / Q000096:biosynthesis; D006867:Hydrolases / Q000096:biosynthesis; D008658:Inactivation, Metabolic; D007531:Isoflurophate / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010634:Phenobarbital / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis; D044345:Phosphoric Triester Hydrolases; D051381:Rats; D011919:Rats, Inbred Strains; D019324:beta-Naphthoflavone
chemical_list: D001571:Benzoflavones; D002800:Cholinesterase Inhibitors; D007531:Isoflurophate; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase; D006867:Hydrolases; D004950:Esterases; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase; D000110:Acetylcholinesterase; D002802:Cholinesterases; D010744:Phosphoric Monoester Hydrolases; D044345:Phosphoric Triester Hydrolases; D043303:Aryldialkylphosphatase; C020061:diisopropyl-fluorophosphatase; D010634:Phenobarbital