Reproductive and sphingolipid metabolic effects of fumonisin B1 and its alkaline hydrolysis product in LM/Bc mice: Hydrolyzed fumonisin B1 did not cause neural tube defects

Kenneth A. Voss, Ronald T. Riley, Maurice E. Snook, Janee Gelineau-van Waes

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Fumonisins are mycotoxins produced by Fusarium verticillioides. They are toxic to animals and exert their effects through mechanisms involving disruption of sphingolipid metabolism. Fumonisins are converted to their hydrolyzed analogs by alkaline cooking (nixtamalization). Both fumonisins and hydrolyzed fumonisins are found in nixtamalized foods such as tortillas, and consumption of tortillas has been implicated as a risk factor for neural tube defects (NTD). Fumonisin B1 (FB1) induced NTD when given (ip) to pregnant LM/Bc mice; however, neither the NTD induction potential of hydrolyzed fumonisin B1 (HFB1) nor its affect on sphingolipid metabolism in pregnant mice have been reported. The teratogenic potential of FB1 and HFB1 was therefore compared using the LM/Bc mouse model. Dams were dosed (ip) with 2.5, 5.0, 10, or 20 mg/kg (≤ 49 μmol/kg) body weight (bw) HFB1 on embryonic day (E)7-E8. Negative and positive control groups were given vehicle or 10 mg/kg (14 μmol/kg) bw FB1, respectively. The high dose of HFB1 disrupted sphingolipid metabolism, albeit slightly, but did not cause maternal liver lesions or NTD (n 5 8-10 litters per group). In contrast, 10 mg/kg bw FB1 markedly disrupted maternal sphingolipid metabolism, caused hepatic apoptosis in the dams, increased fetal death rates, and decreased fetal weights. Furthermore, NTD were found in all FB1-exposed litters (n 5 10), and 66 ± 24% of the fetuses were affected. The findings indicate that HFB1 does not cause NTD in the sensitive LM/Bc mouse model and only weakly disrupts sphingolipid metabolism at doses up to sevenfold higher (micromole per kilogram body weight basis) than the previously reported lowest observed adverse effect level for FB1. Published by Oxford University Press 2009.

Original languageEnglish (US)
Pages (from-to)459-467
Number of pages9
JournalToxicological Sciences
Volume112
Issue number2
DOIs
StatePublished - Sep 25 2009

All Science Journal Classification (ASJC) codes

  • Toxicology

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