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In vivo formation of N-acyl-fumonisin B1

Harrer, Henning, Humpf, Hans Ulrich, Voss, Kenneth A.
Mycotoxin research 2015 v.31 no.1 pp. 33-40
body weight, ceramides, chemical analysis, congenital abnormalities, corn, cytotoxicity, foods, fumonisin B1, humans, hydrolysis, kidneys, liver, mass spectrometry, metabolism, metabolites, rats, risk factors
Fumonisins are fungal toxins found in corn and in corn-based foods. Fumonisin B₁(FB₁) 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 FB₁(HFB₁) also occurs in foods and is metabolized by rats to compounds collectively known as N-acyl-HFB₁(also known as N-acyl-AP₁). N-acyl-HFB₁is structurally similar to ceramides, metabolites which have important structural and signaling functions in cells. FB₁is N-acylated in vitro to ceramide-like metabolites which, like FB₁, are cytotoxic. However, metabolism of FB₁and 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 FB₁on five consecutive days and the liver and kidney thereafter processed for chemical analysis. N-acyl derivatives of fumonisin B₁were identified for the first time in these principal target organs of FB₁in 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 C₁₆derivatives predominating in the kidney and C₂₄derivatives being prevalent in the liver. The toxicological significance of N-acyl-fumonisins is not known and warrants investigation.