In vivo formation of N-acyl-fumonisin B(1)

Fumonisins are fungal toxins found in corn and in corn-based foods. Fumonisin B(1) (FB(1)) is the most common and is toxic to animals, causes cancer in rodents, and is a suspected risk factor for cancer and birth defects in humans. The hydrolyzed form of FB(1) (HFB(1)) also occurs in foods and is metabolized by rats to compounds collectively known as N-acyl-HFB(1) (also known as N-acyl-AP(1)). N-acyl-HFB(1) is structurally similar to ceramides, metabolites which have important structural and signaling functions in cells. FB(1) is N-acylated in vitro to ceramide-like metabolites which, like FB(1), are cytotoxic. However, metabolism of FB(1) and inhibition of ceramide synthase by its metabolites in vivo has not been demonstrated. Male rats were dosed ip with 0.5, 1, or 2 mg/kg body weight FB(1) on five consecutive days and the liver and kidney thereafter processed for chemical analysis. N-acyl derivatives of fumonisin B(1) were identified for the first time in these principal target organs of FB(1) in rats, at levels up to 0.4 nmol/g tissue using mass spectrometry. The N-acyl chain length of the metabolites varied in a tissue-dependent manner with C(16) derivatives predominating in the kidney and C(24) derivatives being prevalent in the liver. The toxicological significance of N-acyl-fumonisins is not known and warrants investigation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12550-014-0211-5) contains supplementary material, which is available to authorized users.