title: Mechanism of inhibition of hepatic bioactivation of paracetamol by dimethyl sulfoxide.
abstract: Prior work has shown that DMSO inhibits paracetamol hepatotoxicity. In this paper we show that DMSO and its reduced metabolite dimethyl sulfide (DMS) can inhibit in vitro hepatic dimethylnitrosamine N-demethylase. We also show that DMSO can inhibit in vivo production of glutathione conjugates of paracetamol. Glutathione is known to conjugate the bioactivated form of paracetamol. Also, the isozyme of cytochrome P-450 responsible for dimethylnitrosomine N-demethylase, cytochrome P-450j, is thought responsible for paracetamol bioactivation. We therefore propose that DMSO inhibits paracetamol hepatotoxicity due to inhibition of cytochrome P-450j-dependent paracetamol bioactivation by DMSO and its metabolite DMS.
authors.affiliation: Institute for Environmental Studies, University of Illinois, Urbana 61801.
authors.forename: E H
authors.initials: EH
authors.lastname: Jeffery
authors.forename: K
authors.initials: K
authors.lastname: Arndt
authors.forename: W M
authors.initials: WM
authors.lastname: Haschek
mesh_terms: D000082:Acetaminophen / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D001711:Biotransformation / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004128:Dimethylnitrosamine / Q000378:metabolism; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D013431:Sulfates / Q000378:metabolism
chemical_list: D005965:Glucuronates; D013431:Sulfates; D000082:Acetaminophen; D005978:Glutathione; D004128:Dimethylnitrosamine; D004121:Dimethyl Sulfoxide