Alcohol and alcoholism (Oxford, Oxfordshire) · 2015
Elevation of Kynurenine Metabolites in Rat Liver and Serum: A Potential Additional Mechanism of the Alcohol Aversive and Anti-cancer Effects of Disulfiram?
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Badawy Abdulla A-B, Bano Samina
Аннотация
AIMS: 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.
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.