Effect of niacin supplementation on nausea-like behaviour in an isoniazid-induced mouse model of pellagra

Abstract

Abstract Niacin deficiency causes pellagra, the symptoms of which include dermatitis, diarrhoea and dementia. Investigating the mechanism underlying these phenotypes has been challenging due to the lack of an appropriate animal model. Here, we report a mouse model of pellagra-related nausea induced by feeding mice a low-niacin diet and administering isoniazid (INH), which is thought to induce pellagra. Mice fed a normal or low-niacin diet received INH (0.3 or 1.0 mg/mg/animal, twice daily, 5 days), and nausea was evaluated based on pica behaviour, which is considered the rodent equivalent of the emetic reflex. Furthermore, the effect of therapeutic niacin administration on nausea was evaluated in this model. Urinary and hepatic metabolite levels were analysed by liquid chromatography coupled with mass spectrometry. INH-induced pica was observed in mice fed a low-niacin diet but not in those fed a normal diet. Levels of urinary metabolites, such as 1-methyl-2-pyridone-5-carboxamide, kynurenic acid and xanthurenic acid, were significantly reduced in the mice treated with INH compared with those that did not receive INH. Furthermore, niacin supplementation prevented pica and restored the levels of some metabolites in this mouse model. Our findings suggest that INH-related nausea is pellagra-like. We also believe that our newly established method for quantifying pica is a useful tool for investigating the mechanisms of pellagra-related nausea.