Protective Effect Of Resveratrol Against Zearalenone-induced Damage In HEK293 Cells

Zearalenone is one of the secondary metabolites produced by Fusarium fungi which are widely distributed in cereals and animal feeds. The structure of ZEA is similar to 17β-Estradiol(one of the main estrogen in human), and it can induce reproductive system disorders among animals and humans. Moreover, ZEA has also been shown to be hepatotoxic, nephrotoxic, haematoxic, immunotoxic and neurotoxic. Thus, it’s urgent to find an effective way to inhibit the toxicity of zearalenone. Resveratrol, a non-flavonoid phenolic, is widely present in grape skins, peanuts and many other plants. Literature reports have proven the beneficial physiological activities of resveratrol in many vivo and vitro research. However, no study on applying it for the prevention of ZEA-induced damage is found in literature. In this study, HEK293 cell line was chosen as the cell model to study the protective effect of resveratrol on ZEA-induced kidney damage, and to elucidate the related mechanism. The main studies and results are as follows:The inhibition rate of cell proliferation was determined after the treatment of ZEA/RSV/LA for 24 hours. And the IC50 value for ZEA was approximately 80 μmol/L,the no-observed-adverse-effect level of RSV was below 10 μmol/L. The cells were pretreated with RSV/LA for 24 hours, and then exposed to ZEA for 24 hours, four indicators were measured: the cell viability, the ROS level, the MDA content and the activity of SOD/Mn-SOD. Fromthe experimental results, we found that the pretreatment of RSV can effectively improve the inhibition of cell proliferation and oxidative damage induced by ZEA, also the same protective effects of LA as a positive control were shown.To further confirm the effects of RSV on ZEA-induced apoptosis, the morphological changes of cell nucleus, mitochondrial membrane potential(MMP), cell cycle distribution and apoptosis rate were analyzed. Pretreatment of RSV showed significant protective effects by reducing the nuclear damages, the loss of MMP, cell cycle arrest and the apoptosis rate. Meanwhile, the up-regulated Bax gene expression, as well as the acetylation of FOXO3 a in ZEA-treated cells were also markedly suppressed by RSV through the up-regulation of SIRT1 and Bcl-2 expression.All these above results demonstrate that RSV can exhibit significant preventive effects on ZEA-induced cell damages, and the effects may be attributed to the up-regulation of SIRT1, which enhances the deacetylation of FOXO3 a and then strengthens the resistance of cells to oxidative stress and apoptosis induced by ZEA exposure.