Furan is a potent liver toxicant and carcinogen in rodents. Humans are exposed to furan through a variety of sources including heat-treated foods, tobacco and wood smoke and air pollution. Furan’s toxic effects requires metabolism. Oxidation by cytochrome P450 2E1 catalysis leads to the formation of a reactive α,β-unsaturated dialdehyde, <i>cis</i>-2-butene-1,4-dial (BDA). BDA is toxic and mutagenic to cells and consequently is considered responsible for the toxic effects of furan. In vitro, this compound reacts readily with protein and DNA nucleophiles. Studies in hepatocytes demonstrated that the reaction of BDA with glutathione (GSH) generates a different spectrum of reaction products in which BDA crosslinks GSH to wide variety of cellular amines including protein lysine residues, amino acids and polyamines. The relative amounts of these two reactive compounds is determined in part by the concentration of GSH present in the cell. Analysis of urinary metabolites provides evidence that both electrophilic metabolites are formed in vivo. The role of these two reactive metabolites in the overall toxic and carcinogenic effects of furan requires further study.  Understanding the contributions of each metabolite to the overall toxic and carcinogenic properties of furan will assist the assessment of risk associated human furan exposure.

Biological targets of electrophilic furan metabolites

256th National Meeting (2018)

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