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In vivo formation of N-acyl-fumonisin B1

Author:
Harrer, Henning, Humpf, Hans Ulrich, Voss, Kenneth A.
Source:
Mycotoxin research 2015 v.31 no.1 pp. 33-40
ISSN:
0178-7888
Subject:
body weight, ceramides, chemical analysis, congenital abnormalities, corn, cytotoxicity, foods, fumonisin B1, humans, hydrolysis, kidneys, liver, mass spectrometry, metabolism, metabolites, rats, risk factors
Abstract:
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.
Agid:
1201009