Metabolism of organophosphorus insecticides by liver homogenates from different species

Abstract

The rates of disappearance of parathion, diazinon, ethion, phorate, Di-Syston (disulfoton), methyl-parathion, Guthion (aziaphosmethyl), and ronnel effected by a hepatic oxidative desulfurating system of four different species in the presence of NAD and NADP were determined. The rates of disappearance of the last three insecticides effected by the demethylating system in the presence of reduced glutathione have been determined also. The parent insecticides were determined by gas–liquid chromatography after extracting them from the incubation mixture with hexane. The conversion products formed by the oxidative system were detected by carboxylesterase inhibition on thin-layer chromatographic plates. Inhibitors were detected in extracts from the incubation mixtures of all liver homogenates with all the insecticides studied except phorate and Di-Syston. The rates of disappearance of phorate and Di-Syston were considerably higher than the rates for the other compounds with all the liver homogenates studied except female chicken liver. Methylparathion, Guthion, and ronnel were metabolized by both systems, but the demethylating system was more active for the three compounds. The rates of disappearance of the different insecticides effected by the oxidative system were considerably less when incubated with female chicken livers than with male chicken livers. These differences were not observed with the demethylating system. The rat, guinea pig, and monkey liver homogenates were all uniformly active in metabolizing the different insecticides by the oxidative system.

Acute toxicity and metabolism of pesticides in birds

“…50) The post-mitochondrial subcellular fraction (S9) of the chicken liver exhibited 2-50 times sex differences (male >> female) in the oxidative degradation of eight OPs. 52) The hepatic ADase activity was 1.1-4.8-fold higher than the renal activity in the chicken, turkey, duck, and goose, 27) indicating the liver's greater importance in pesticide metabolism. The alimentary tract may play a role in the metabolism of pesticides when considering its organ weight relative to the liver.…”

“…GSTs, the homo or heterodimers with each subunit having a molecular weight of 24-28 kDa, catalyze the reaction of glutathione at the electrophilic site of a pesticide and its metabolites, 83) as reported for the O-demethylation of many OP pesticides. 52,84,85) The intact glutathione conjugate has been detected rarely in the avian metabolism, 86,87) due to the successive metabolism by peptidases and N-acetyltransferases finally to form a mercapturic acid conjugate. 83) When the herbicide propachlor was orally administered to hens, the cysteine and mercapturic acid conjugated via the reaction of glutathione at the chloromethyl carbon were detected as the main metabolites in the excreta.…”

“…In vitro metabolism of three OPs by using liver homogenates showed less O-demethylation in the chicken than in mammals. 52) Hepatic GST activity against 1,2-dichloro-4-nitrobenzene (DCNB) was reported to be much lower in the turkey than in the rat, but comparable activity against CDNB was observed in both species. 90) In the kidney of the Japanese quail, the GST activity against DCNB was comparable to the hepatic activity.…”

Distribution and Elimination of14C-Ethion Insecticide in Chamomile Flowers and Oil

“…Like other organothiophosphate insecticides (chlorpyrifos, parathion), ethion is converted via desulfuration in the liver by cytochrome P-450 enzymes to its active oxygen analog, ethion monooxon. 26 It is not known whether ethion monooxon can then be desulfurated to ethion dioxon. Ethion monooxon is a potent inhibitor of cholinesterases and exerts toxicity by reacting with an inhibiting neural acetylcholinesterase.…”

In vitro metabolism of vamidothion and its thio analog by rat and mouse liver

“…The oxidation of the thioether moiety in organophosphorus insecticides to the sulfoxide has been observed in plants in vivo (Metcalf et al, 1954(Metcalf et al, ,1955(Metcalf et al, ,1957Fukuto et al, 1956;Fukuto and Metcalf, 1969) and in animals in vivo and in vitro (Rao and McKinley, 1969;Bull et al, 1970;Bull and Stokes, 1970;Bull, 1965Bull, ,1972). In the case of the thioate and dithioate triesters containing a thioether moiety, the compound is subject to oxidation at both sites (Bowman and Casida, 1958).…”