Reproductive and sphingolipid metabolic effects of fumonisin B(1) and its alkaline hydrolysis product in LM/Bc mice: hydrolyzed fumonisin B(1) did not cause neural tube defects.
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 B(1) (FB(1)) induced NTD when given (ip) to pregnant LM/Bc mice; however, neither the NTD induction potential of hydrolyzed fumonisin B(1) (HFB(1)) nor its affect on sphingolipid metabolism in pregnant mice have been reported. The teratogenic potential of FB(1) and HFB(1) was therefore compared using the LM/Bc mouse model. Dams were dosed (ip) with 2.5, 5.0, 10, or 20 mg/kg (< or = 49 micromol/kg) body weight (bw) HFB(1) on embryonic day (E)7-E8. Negative and positive control groups were given vehicle or 10 mg/kg (14 micromol/kg) bw FB(1), respectively. The high dose of HFB(1) disrupted sphingolipid metabolism, albeit slightly, but did not cause maternal liver lesions or NTD (n = 8-10 litters per group). In contrast, 10 mg/kg bw FB(1) 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 FB(1)-exposed litters (n = 10), and 66 +/- 24% of the fetuses were affected. The findings indicate that HFB(1) 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 FB(1).
Voss
Kenneth A
KA
Toxicology & Mycotoxin Research Unit, United States Department of Agriculture, Agricultural Research Service, Athens, Georgia 30604-5677, USA. ken.voss@ars.usda.gov
Riley
Ronald T
RT
Snook
Maurice E
ME
Waes
Janee Gelineau-van
JG
D000818:Animals; D005260:Female; D037341:Fumonisins / Q000378:metabolism / Q000633:toxicity*; D006868:Hydrolysis; D051379:Mice; D009436:Neural Tube Defects / Q000209:etiology* / Q000473:pathology; D011247:Pregnancy; D012098:Reproduction / Q000187:drug effects*; D012307:Risk Factors; D013107:Sphingolipids / Q000378:metabolism*
D037341:Fumonisins; D013107:Sphingolipids; C056933:fumonisin B1