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ARS Home » Southeast Area » Athens, Georgia » U.S. National Poultry Research Center » Toxicology & Mycotoxin Research » Research » Publications at this Location » Publication #309487
Title: In vivo formation of N-acyl-fumonisin B1

Author
item HARRER, HENNING - Muenster University
item HUMPF, HANS-ULRICH - Muenster University
item Voss, Kenneth

Submitted to: Mycotoxin Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/27/2014
Publication Date: 2/1/2015
Citation: Harrer, H., Humpf, H., Voss, K.A. 2015. In vivo formation of N-acyl-fumonisin B1. Mycotoxin Research. 31(1):33-40.

Interpretive Summary: 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-HFB1 is structurally similar to ceramides, metabolites which have important structural and signaling functions in cells. To determine if FB1 is also metabolized, rats were given FB1 or, for comparative purposes, HFB1. Analysis of liver and kidney tissues revealed the metabolism of FB1 to novel, ceramide-like N-acyl-FB1 metabolites. Up to 60 percent of the total FB1 species (unmetabolized FB1 plus N-acyl-FB1 metabolites) in the liver were metabolites. In contrast, metabolites accounted for less than 10 percent of the FB1 species in kidney while N-acyl-HFB1 made up 60 to 65 percent of the total HFB1 species in both organs. This is the first demonstration of FB1 metabolism in animals. Studies are needed to determine the toxicological significance of the metabolites.

Technical 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-HFB1 is structurally similar to ceramides, metabolites which have important structural and signaling functions in cells. FB1 is N-acylated in vitro to ceramide-like metabolites which, like FB1, are cytotoxic. However, metabolism of FB1 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 FB1 on five consecutive days and the liver and kidney thereafter processed for chemical analysis. N-acyl-derivatives of fumonisin B1 were identified for the first time in these principal target organs of FB1 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 C16-derivatives predominating in kidney and C24-derivatives being prevalent in the liver. The toxicological significance of N-acyl-fumonisins is not known and warrants investigation.