Ameliorative effect of Silybin on bisphenol A induced oxidative stress, cell proliferation and steroid hormones oxidation in HepG2 cell cultures
Ameliorative effect of Silybin on bisphenol A induced oxidative stress, cell proliferation and steroid hormones oxidation in HepG2 cell cultures
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DOI：
10.1038/s41598-019-40105-8
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发表时间：
2019-03-01
影响因子：
4.6
通讯作者：
Stiuso, Paola
中科院分区：
文献类型：
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作者：
Lama, Stefania;Vanacore, Daniela;Stiuso, Paola
双酚A （BPA）和水飞蓟宾被认为是异种雌激素，可以干扰内源性激素的作用。与脂肪变性（NAFL）患者相比，非酒精性脂肪性肝炎（NASH）患者血浆中BPA水平较高。我们研究了双酚a和水飞蓟宾单独或联合作用对高浓度葡萄糖培养基（H-HepG2）中HepG2细胞增殖、氧化应激和类固醇代谢的影响。加入3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑（MTT）评估细胞活力。用分光光度法定量TBARS。Western blot检测双酚a、水飞蓟宾及其联合使用对磷酸化细胞外信号调节激酶（ERK）、ERK和Caspase 3表达的影响。脂质和类固醇激素的鉴定采用质谱法。BPA引发H-HepG2氧化应激和类固醇激素氧化，形成具有雌激素和遗传毒性的代谢物。水飞蓟宾改善了有害的bpa诱导作用，降低了葡萄糖摄取和脂质过氧化。水飞蓟宾还能激活维生素D3代谢产物的合成，防止类固醇激素氧化。BPA可能是NAFLD恶化和发展的重要危险因素。同时，水飞蓟宾可能是一种有效的支持，以抵消NASH患者的这些影响。
Bisphenol A (BPA) and silybin are considered xenoestrogens and could interfere with the action of endogenous hormones. It was demonstrated a higher level of BPA in plasma of nonalcoholic steatohepatitis (NASH) patients, compared to those with steatosis (NAFL). We investigated the effect of BPA and silybin, alone or in combination, on proliferation, oxidative stress and steroid metabolism in HepG2 grown in high glucose concentration medium (H-HepG2). Cell viability was assessed by adding 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). TBARS were quantified by spectrophotometry. The effect of BPA, silybin and their combination on the expression of phosphorilized extracellular signal-regulated kinase (ERK), ERK and Caspase 3 was determined by Western blot analysis. The identifications of lipids and steroid hormones was performed by mass spectrometry. BPA elicited in H-HepG2 oxidative stress and steroid hormones oxidation leading to the formation of metabolite with estrogenic and genotoxic potentials. Silybin ameliorates the harmful BPA-induced effect decreasing glucose uptake and lipid peroxidation. Moreover silybin activates the synthesis of vitamin D3 metabolites and prevent the steroid hormones oxidation. BPA could be considered as an important risk factor in worsening and progression of NAFLD. At the same time silybin could be a valid support to counteract these effects in NASH patients.