Examination of the metabolism in vitro of parathion (diethyl p-nitrophenyl phosphorothionate) by rat lung and brain

Abstract

These studies have indicated there is present in rat lung microsomes a mixed-function oxidase enzyme system capable of metabolizing parathion to paraoxon and to diethyl phosphorothioic acid. In addition, analogous to previous results using rat liver microsomes, the sulfur atom released in the metabolism of parathion to paraoxon was found to covalently bind to lung microsomes. In contrast to liver, the metabolism of parathion by rat lung microsomes is not inducible by pretreatment of the animals with phenobarbital or 3-methylcholanthrene. The metabolism of parathion by lung microsomes is stimulated by NADPH and oxygen and is inhibited by carbon monoxide, anaerobic conditions, SKF-525A and piperonyl butoxide. There is also present in a particulate fraction of rat brain equivalent to microsomes an enzyme or enzyme system capable of metabolizing parathion to paraoxon and to diethyl phosphorothioic acid. The metabolism of parathion to paraoxon by rat brain microsomes is also accompanied by the release and covalent binding of the sulfur atom of parathion. The activity in rat brain microsomes is stimulated by oxygen and NADPH and inhibited by carbon monoxide, anaerobic conditions, SKF-525A and piperonyl butoxide. These data suggest that cytochrome P-450-containing mixed-function oxidase enzyme systems are responsible for the NADPH-stimulaled catalytic activity toward parathion found in rat lung and rat brain microsomes.