Biotransformation of the insecticide parathion by mouse brain.
The acute toxicity of organothiophosphate insecticides like parathion results from their metabolic activation by cytochromes P450. The present study is directed towards the characterization of cytochrome-P450-dependent metabolism of parathion by various mouse brain regions. Intraperitoneal administration of [35S]parathion to mice led to covalently bound [35S]sulfur in various tissues, indicating their capacity to oxidatively desulfurate this insecticide. Liver contained the greatest amount of covalently bound sulfur, and brain the least. Among individual brain regions the olfactory bulb and hypothalamus possessed the highest levels of sulfur binding when expressed on a per milligram tissue basis. However, when expressed on a per brain region basis, sulfur binding was greatest within the cortex as a result of the large mass of this region, compared to the hypothalamus and olfactory bulb. Incubation of the 78,000 x g fraction of mouse brain with parathion resulted in formation of p-nitrophenol, although paraoxon could not be detected. However, given the current understanding of parathion metabolism by cytochromes P450, and given that paraoxon can rapidly disappear through phosphorylation of serine hydroxyl groups, it is reasonable to assume that at least some paraoxon was formed. Production of p-nitrophenol required NADPH and was inhibited by carbon monoxide. In vitro incubations of parathion with the 78,000 x g fraction of mouse brain indicated that the hypothalamus and olfactory bulb had the greatest capacity to produce p-nitrophenol. These results demonstrate that various mouse brain regions possess different capacities to metabolize parathion.
Soranno
T M
TM
Department of Pharmacology and Toxicology, University of Medicine and Dentistry of New Jersey, Newark 07103-2757.
Sultatos
L G
LG
D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D008297:Male; D051379:Mice; D009596:Nitrophenols / Q000378:metabolism; D010278:Parathion / Q000378:metabolism*; D013455:Sulfur / Q000378:metabolism
D009596:Nitrophenols; D010278:Parathion; D013455:Sulfur; D003577:Cytochrome P-450 Enzyme System; C024836:4-nitrophenol