New insights into methylfuran metabolism

Abstract

Methylfurans like 2,5-dimethylfuran (DMF), 2-methylfuran (2-MF), and 3-methylfuran (3‑MF) are heat-induced contaminants present in a variety of foods, such as coffee, roasted nuts and canned foods. Concerning their metabolism, toxicity, and safety information is scarce. Several studies indicate that cytochrome P450 mediated epoxidation resembles the main route of biotransformation for furan and different methylfurans, leading to the formation of highly reactive α, β-unsaturated dicarbonyls, suggested to be responsible for their reported hepatotoxic and potentially carcinogenic effects. It is assumed that side-chain oxidation by CYPs might represent an additional metabolic route for alkylfurans. The resulting alcohols may be rapidly oxidized to the corresponding carboxylic acid or serve as a substrate for sulfotransferases, which may also lead to the formation of reactive intermediates. To verify whether DMF is subject to unilateral side-chain hydroxylation, formation of 5-methyl-2-furfuryl alcohol and respective higher oxidized metabolites 5-methyl-2-furfural and 5-methyl-2-furancarboxylic acid were investigated in incubations of human liver microsomes using an established and validated GC-MS method. It was possible to monitor time- and concentration dependence of the formation of 5-methyl-2-furfuryl alcohol, while only minimal concentrations of higher oxidized metabolites were detected. In addition, side-chain oxidation of 2-MF and 3-MF were also investigated using an equivalent approach. However, formation of 2- and 3-furfuryl alcohol was not observed in human liver microsomal incubations, indicating structure dependence in metabolism of different alkyl furans.

Keywords: 2,5-dimethylfuran; 2-methylfuran; 3-methylfuran; GC-MS; human metabolism.