Catechins protect against acrylamide- and glycidamide-induced cellular toxicity via rescuing cellular apoptosis and DNA damage.
Catechins protect against acrylamide- and glycidamide-induced cellular toxicity via rescuing cellular apoptosis and DNA damage.
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DOI：
10.1016/j.fct.2022.113253
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发表时间：
2022-06
期刊：
影响因子：
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通讯作者：
Anli Wang;Xinyu Chen;Lai Wang;Wei Jia;Xuzhi Wan;J. Jiao;Weixuan Yao;Yu Zhang
中科院分区：
文献类型：
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作者：
Anli Wang;Xinyu Chen;Lai Wang;Wei Jia;Xuzhi Wan;J. Jiao;Weixuan Yao;Yu Zhang
丙烯酰胺（AA）存在于各种环境和饮食来源中，并作为一种可能的致癌物质引起了广泛关注。甘氨酰脲（GA）是通过P450 2 E1（CYP 2 E1）的主要遗传毒性代谢产物。在本研究中，我们研究了（-）-表没食子儿茶素没食子酸酯（EGCG）和（-）-表儿茶素（EC）对AA和GA诱导的HepG 2细胞肝毒性的保护作用。结果表明，EC和EGCG抑制AA和GA诱导的细胞毒作用和EPA介导的细胞凋亡。此外，AA（100 μg/mL）和GA（50 μg/mL）暴露引起细胞周期停滞和DNA损伤，而EC和EGCG在12.5 - 50 μg/mL范围内挽救细胞周期停滞并抑制DNA损伤。EC和EGCG对AA（100 μg/mL）和GA（50 μg/mL）处理HepG 2细胞24 h后Bax和Caspase 3蛋白表达的影响均显著低于对照组。EC或EGCG的干预可上调DNA修复相关蛋白PARP的表达，下调Cleaved-PARP的表达。此外，EC对AA和GA诱导的HepG 2细胞毒性的保护作用优于EGCG。总之，EC和EGCG可通过挽救细胞凋亡和DNA损伤，以及促进细胞周期进程，有效地保护AA和GA诱导的HepG 2细胞肝毒性。
Acrylamide (AA) occurs in both various environmental and dietary sources and has raised widespread concern as a probable carcinogen. Glycidamide (GA) is the main genotoxic metabolite through P450 2E1 (CYP2E1). In the present study, we investigated the protective effect of (−)-epigallocatechin gallate (EGCG) and (−)-epicatechin (EC) against AA- and GA-induced hepatotoxicity in HepG2 cells. The results demonstrated that EC and EGCG inhibited AA- and GA-induced cytotoxicity and mitochondria-mediated cellular apoptosis. Moreover, exposure to AA (100 μg/mL) and GA (50 μg/mL) caused cell cycle arrest and DNA damage, while EC and EGCG ranging from 12.5 to 50 μg/mL rescued cell cycle arrest and inhibited DNA damage. Furthermore, EC and EGCG down-regulated pro-apoptotic protein Bax and Caspase 3 after a 24-h treatment in HepG2 cells exposed to AA (100 μg/mL) or GA (50 μg/mL). Also, the intervention with EC or EGCG up-regulated the expression of DNA repair related protein PARP and down-regulated the expression of Cleaved-PARP. Besides, EC exerted better protective effect than EGCG against AA- and GA-induced cytotoxicity in HepG2 cells. Altogether, EC and EGCG were effective in protecting AA- and GA-induced hepatotoxicity via rescuing cellular apoptosis and DNA damage, as well as promoting cell cycle progression in HepG2 cells.