In vivo formation of TV-acyl-fumonisin Bi

摘要

Fumonisins are fungal toxins found in corn and in corn-based foods. Fumonisin Bi (FBi) 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 ofFBi (HFBj) also occurs in foods and is metabolized by rats to compounds collectively known as N-acyl-HFBi (also known as N-acyl-APi). jV-acyl-HFBi is structurally similar to ceramides, metabolites which have important structural and signaling functions in cells. FBi is N-acylated in vitro to ceramide-like metabolites which, like FBi, are cytotoxic. However, metabolism of FBi and inhibition of ceramide synthase by its metabolites in vivo has not been demonstrated. Male rats were dosed ip with 0.5, 1, or2 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 Bj were identified for the first time in these principal target organs of FB! in rats, at levels up to0.4 nmol/g tissue using mass spectrometry. The iV-acyl chain length of the metabolites varied in a tissue-dependent manner with C_(16) derivatives predominating in the kidney andC_(24) derivatives being prevalent in the liver. The toxicological significance of A/-acyl-fumonisins is not known and warrants investigation.