Abstract
Fumonisin contaminates food and feed extensively throughout the world, causing chronic and acute toxicity in human and animals. Currently, studies on the toxicology of fumonisins mainly focus on fumonisin B1 (FB1). Considering that FB1, fumonisin B2 (FB2) and fumonisin B3 (FB3) could coexist in food and feed, a study regarding a single toxin, FB1, may not completely reflect the toxicity of fumonisin. The gastrointestinal tract is usually exposed to these dietary toxins. In our study, the human gastric epithelial cell line (GES-1) was used as in vitro model to evaluate the toxicity of fumonisin. Firstly, we found that they could cause a decrease in cell viability, and increase in membrane leakage, cell death and the induction of expression of markers for endoplasmic reticulum (ER) stress. Their toxicity potency rank is FB1 > FB2 >> FB3. The results also showed that the synergistic effect appeared in the combinations of FB1 + FB2 and FB1 + FB3. Nevertheless, the combinations of FB2 + FB3 and FB1 + FB2 + FB3 showed a synergistic effect at low concentration and an antagonistic effect at high concentration. We also found that myriocin (ISP-1) could alleviate the cytotoxicity induced by fumonisin in GES-1 cells. Finally, this study may help to determine or optimize the legal limits and risk assessment method of mycotoxins in food and feed and provide a potential method to block the fumonisin toxicity.
Highlights
As akin natural contaminators produced by Fusarium, Fusarium mycotoxins are not necessary for fungal growth, while they can fertilize the process of crop infection and cause plant diseases [1–3]
We examined whether the disruption of a sphingolipid metabolism plays an important role in the GES-1 cytotoxicity induced by fumonisin B2 (FB2) and fumonisin B3 (FB3)
We found that ISP-1 could alleviate the cytotoxicity induced by FBs in GES-1 cell and even enable to recover it to the same level as the control group in the FB2 treated group
Summary
As akin natural contaminators produced by Fusarium, Fusarium mycotoxins are not necessary for fungal growth, while they can fertilize the process of crop infection and cause plant diseases [1–3]. We assessed the combined toxicity of the fumonisin mixtures and the remission effect of myriocin (ISP-1) These data provide a new reference for establishing and optimizing the law and regulation regarding the safety of mycotoxins and a novel channel to block FBs toxicity. CCoommbbiinneeddTTooxxiicciittyy ooff FFBB11,, FFBB22 aanndd FFBB33 iinn GGEESS--11 CCeellllss TThhee cceellll vviiaabbiilliittyy ooff tthhee ddoossee––eeffffeecctt rreellaattiioonnsshhiipp ccuurrvvee ffoorr tthhee ttooxxiicciittyy ooff tthhee tteesstteedd mmiixxttuurree wwaass sshhoowwnn iinn FFiigguurree 55. IInntteerraaccttiivveeeeffffeeccttss ooff FFBB11,, FFBB22 aanndd FFBB33 oonn tthhee GGEESS--11 cceellll vviiaabbiilliittyy.. The results showed that the mixtures of FB1 + FB2 and FB1 + FB3 almost produced synergistic cytotoxicity against GES-1 cells at any level (IC10–IC75). At the low cell inhibition level (IC10–IC25), the FB1 + FB2 + FB3 combination produced a synergistic effect and an antagonistic effect at the high cytotoxicity level.
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