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. 2016 Jan;51(1):20-6.
doi: 10.1093/alcalc/agv085. Epub 2015 Jul 29.

Elevation of Kynurenine Metabolites in Rat Liver and Serum: A Potential Additional Mechanism of the Alcohol Aversive and Anti-cancer Effects of Disulfiram?

Abdulla A-B Badawy  1 , Samina Bano  2
Affiliations

Elevation of Kynurenine Metabolites in Rat Liver and Serum: A Potential Additional Mechanism of the Alcohol Aversive and Anti-cancer Effects of Disulfiram?

Abdulla A-B Badawy et al. Alcohol Alcohol. 2016 Jan.

Abstract

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.

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Figures

Fig. 1.
Fig. 1.
The hepatic kynurenine pathway of tryptophan degradation up to the kynureninase step. Abbreviations are in parentheses. Benserazide is shown as a kynureninase inhibitor.
Fig. 2.
Fig. 2.
Body weights of control (C) and disulfiram (DS)-treated rats. Values are means ± SEM for each group of five rats.
Fig. 3.
Fig. 3.
Metabolism of disulfiram.
See this image and copyright information in PMC

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References

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