title: Elevation of Kynurenine Metabolites in Rat Liver and Serum: A Potential Additional Mechanism of the Alcohol Aversive and Anti-cancer Effects of Disulfiram?
abstract: OBJECTIVE
  The tryptophan metabolites 3-hydroxykynurenine (3-HK) and 3-hydroxyanthranilic acid (3-HAA) inhibit the liver mitochondrial low Km aldehyde dehydrogenase and possess alcohol-aversive and immunosuppressant properties. As the disulfiram (DS) metabolite carbon disulphide activates enzymes forming 3-HK and 3-HAA, we investigated if repeated disulfiram treatment increases the hepatic and serum levels of these 2 metabolites.
  
  
  METHODS
  Livers and sera of male Wistar rats were analysed for tryptophan and kynurenine metabolites after repeated DS treatment for 7 days.
  
  
  RESULTS
  DS increased liver and serum [3-HK] and [3-HAA] possibly by increasing the flux of tryptophan down the hepatic kynurenine pathway and activation of kynurenine hydroxylase and kynureninase.
  
  
  CONCLUSIONS
  We provisionally suggest that elevation of some kynurenine metabolites may be an additional mechanism of the alcohol-aversive and anticancer effects of disulfiram.
authors.affiliation: School of Health Sciences, Cardiff Metropolitan University, Western Avenue, Cardiff CF5 2YB, UK ABadawy@cardiffmet.ac.uk.
authors.forename: Abdulla A-B
authors.initials: AA
authors.lastname: Badawy
authors.affiliation: Present address: Department of Biochemistry, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Samina
authors.initials: S
authors.lastname: Bano
mesh_terms: D015095:3-Hydroxyanthranilic Acid / Q000378:metabolism*; D000427:Alcohol Deterrents / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004221:Disulfiram / Q000494:pharmacology*; D006867:Hydrolases / Q000187:drug effects / Q000378:metabolism; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000187:drug effects / Q000378:metabolism; D050601:Kynurenine 3-Monooxygenase / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D000637:Transaminases / Q000187:drug effects / Q000378:metabolism; D014364:Tryptophan / Q000187:drug effects / Q000378:metabolism
chemical_list: D000427:Alcohol Deterrents; D015095:3-Hydroxyanthranilic Acid; C005045:3-hydroxykynurenine; D007737:Kynurenine; D014364:Tryptophan; D050601:Kynurenine 3-Monooxygenase; D000637:Transaminases; C021481:kynurenine-oxoglutarate transaminase; D006867:Hydrolases; C021480:kynureninase; D004221:Disulfiram