Induction or inhibition of cytochrome P450 2E1 modifies the acute toxicity of acrylonitrile in rats: biochemical evidence

Archives of Toxicology
Wang SuhuaM Aschner

Abstract

The present study was designed to examine the effects of the inhibition or induction of CYP2E1 activity on acute acrylonitrile (AN) toxicity in rats. Increased or decreased hepatic CYP2E1 activity was achieved by pretreatment with acetone or trans-1,2-dichloroethylene (DCE), respectively. AN (50 mg/kg) was administered by intraperitoneal injection. Onset of convulsions and death were observed in rats with increased CYP2E1 activity, whereas convulsions and death did not appear in rats within 1 h after treatment with AN alone. Convulsions occurred in all AN-treated animals with increased CYP2E1 activity at approximately 18 min. The levels of cyanide (CN(-)), a terminal metabolite of AN, were significantly increased in the brains and livers of the AN-treated rats with increased CYP2E1 activity, compared with the levels in rats treated with AN alone, DCE + AN or acetone + DCE + AN. The cytochrome c oxidase (CcOx) activities in the brains and livers of the rats treated with AN or AN + acetone were significantly lower than those in the normal control rats and the rats treated with DCE, whereas the CcOx activities in the brains and livers of rats with decreased CYP2E1 activity were significantly higher than those in AN-treated rats. B...Continue Reading

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Citations

Nov 9, 2011·Toxicology Letters·Nadia M HamdyAshraf B Abdel-Naim
Aug 2, 2013·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Evan O GreggMichael McEwan
Apr 4, 2013·Dose-response : a Publication of International Hormesis Society·He YuanqingDejan Milatovic
Jun 13, 2020·Chemical Research in Toxicology·Vernon E WalkerJames A Swenberg

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