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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 #299924
Title: In vivo metabolism of fumonisin B1 to N-acylated ceramide-like compounds

Author
item Voss, Kenneth
item HARRER, HENNING - University Of Munster
item Riley, Ronald
item HUMPF, HANS-ULRICH - University Of Munster

Submitted to: Society of Toxicology
Publication Type: Abstract Only
Publication Acceptance Date: 3/23/2014
Publication Date: 3/23/2014
Citation: Voss, K.A., Harrer, H., Riley, R.T., Humpf, H. 2014. In vivo metabolism of fumonisin B1 to N-acylated ceramide-like compounds. Society of Toxicology. March 23-27,2014. Phoenix, Arizona.

Interpretive Summary: Abstract - no summary required.

Technical Abstract: Fumonisins are toxic and carcinogenic mycotoxins found in corn-based foods. Fumonisin B1 (FB1) metabolism to ceramide-like cytotoxic N-acylated FB1 (NAFB1) compounds has been shown in vitro, but in vivo metabolism has not been reported. Therefore, male Sprague-Dawley rats (2/group) were given 5 daily ip doses of 0 (vehicle), 0.5, 1.0 or 2.0 mg/kg body weight (BW) FB1 (= 0.69, 1.38 and 2.77 µmol/kg BW, respectively). A positive control group was similarly treated with 1.0 mg/kg BW (2.47 µmol/kg BW) hydrolyzed FB1 (HFB1), an FB1 derivative that is metabolized by rats. After the animals were euthanized, FB1, HFB1 and their N-acyl metabolites were quantified in liver and kidney by HPLC-MS/MS analysis. Unmetabolized FB1 accumulated in kidney in a dose-related manner at concentrations of up to 10 nmol/g tissue. Its concentrations in liver were 12 to 20-fold lower. In contrast, more HFB1 (1.8 nmol/g) was found in liver than in kidneys (0.3 nmol/g). Low levels of NAFB1 and N-acylated HFB1 species (NAHFB1) were found in both tissues. Metabolites having longer fatty acyl chains predominated in liver whereas those with shorter chains were prevalent in kidney: the different chain lengths likely reflecting differences in tissue-specific ceramide synthase isoforms. Metabolite concentrations decreased in the order: NAHFB1 in liver > NAHFB1 in liver > NAFB1 in liver > or = NAFB1 in kidney. Recoveries (% of dose) of total FB1 species from the tissues were < 1%. Recovery of HFB1 species was more variable ranging from about 0.1% in kidney to about 2% in liver. Except for FB1 in kidney, where unmetabolized FB1 was predominant, recoveries (µmolar basis) of parent and metabolites from the tissues were similar. The results show that FB1 is metabolized by ceramide synthases in vivo to N-acylated ceramide-like compounds. Additional studies are needed to determine the toxicological significance of the NAFB1 and NAHFB1 metabolites.