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 language | English |
|---|---|
| Pages (from-to) | 459-467 |
| Number of pages | 9 |
| Journal | Toxicological Sciences |
| Volume | 112 |
| Issue number | 2 |
| DOIs | |
| State | Published - Sep 25 2009 |
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All Science Journal Classification (ASJC) codes
- Toxicology
- Medicine(all)
Cite this
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. / Voss, Kenneth A.; Riley, Ronald T.; Snook, Maurice E.; Gelineau-van Waes, Janee.
In: Toxicological Sciences, Vol. 112, No. 2, 25.09.2009, p. 459-467.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reproductive and sphingolipid metabolic effects of fumonisin B1 and its alkaline hydrolysis product in LM/Bc mice
T2 - Hydrolyzed fumonisin B1 did not cause neural tube defects
AU - Voss, Kenneth A.
AU - Riley, Ronald T.
AU - Snook, Maurice E.
AU - Gelineau-van Waes, Janee
PY - 2009/9/25
Y1 - 2009/9/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=74949127040&partnerID=8YFLogxK
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U2 - 10.1093/toxsci/kfp215
DO - 10.1093/toxsci/kfp215
M3 - Article
C2 - 19783636
AN - SCOPUS:74949127040
VL - 112
SP - 459
EP - 467
JO - Toxicological Sciences
JF - Toxicological Sciences
SN - 1096-6080
IS - 2
ER -