title: Studies on the metabolism of the thiofurans furfuryl mercaptan and 2-methyl-3-furanthiol in rat liver.
abstract: The metabolism of two thiofurans, namely furfuryl mercaptan (FM) and 2-methyl-3-furanthiol (MTF), to their corresponding methyl sulphide and methyl sulphoxide derivatives has been studied in male Sprague-Dawley rat hepatocytes and liver microsomes. Rat hepatocytes converted FM to furfuryl methyl sulphoxide (FMSO) and MTF to 2-methyl-3-(methylthio)furan sulphoxide (MMFSO). Liver microsomes catalysed the NADPH-dependent metabolism of furfuryl methyl sulphide (FMS) to FMSO and 2-methyl-3-(methylthio)furan sulphide (MMFS) to MMFSO. FMS and MMFS metabolism to their thiofuran methyl sulphoxide derivatives was induced by the treatment of rats with Aroclor 1254 and inhibited in liver microsomes treated with 1-aminobenzotriazole. The NADPH-dependent metabolism of FM to FMSO and MTF to MMFSO in liver microsomes was observed in the presence of S-adenosylmethionine. In summary, both thiofurans can be metabolised in rat liver to their thiofuran methyl sulphide derivatives which can be subsequently S-oxidised to form thiofuran methyl sulphoxides. FM and MTF appear to be substrates for rat hepatic microsomal thiol methyltransferase and the S-oxidation of FMS and MMFS appears to be primarily catalysed by cytochrome P450 forms.
authors.affiliation: BIBRA International Ltd, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK. blake@bibra.co.uk
authors.forename: Brian G
authors.initials: BG
authors.lastname: Lake
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Price
authors.forename: David G
authors.initials: DG
authors.lastname: Walters
authors.forename: John C
authors.initials: JC
authors.lastname: Phillips
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Young
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Adams
mesh_terms: D000465:Algorithms; D000818:Animals; D020111:Chlorodiphenyl (54% Chlorine) / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005663:Furans / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008780:Methyltransferases / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology
chemical_list: D005663:Furans; D013438:Sulfhydryl Compounds; D014230:Triazoles; D020111:Chlorodiphenyl (54% Chlorine); C033020:1-aminobenzotriazole; C455106:furfuryl mercaptan; D003577:Cytochrome P-450 Enzyme System; D008995:Monoamine Oxidase; D009247:NADH, NADPH Oxidoreductases; D008780:Methyltransferases; C022742:thiol S-methyltransferase; C443400:2-methyl-3-furanthiol