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芹菜素对乙基多杀菌素诱导的人外周血淋巴细胞氧化应激、DNA 损伤和凋亡细胞死亡的缓解作用。

Mitigating effects of apigenin on edifenphos-induced oxidative stress, DNA damage and apoptotic cell death in human peripheral blood lymphocytes.

机构信息

Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, 202002, Uttar Pradesh, India.

Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, 202002, Uttar Pradesh, India.

出版信息

Food Chem Toxicol. 2019 May;127:218-227. doi: 10.1016/j.fct.2019.03.034. Epub 2019 Mar 22.

DOI:10.1016/j.fct.2019.03.034
PMID:30910686
Abstract

Edifenphos (EDF) is an Organophosphorus pesticide and used in agriculture for pest control. However, EDF has been shown to accumulate in agricultural products and causes hazards to human health. Although reports are available regarding environmental impact of EDF, toxic effects of EDF on human cellular system especially immune cells have not been elucidated. In this study, genotoxicity and cytotoxicity of EDF on human peripheral blood lymphocytes and its amelioration by apigenin (dietary flavonoid) was investigated. We demonstrated that EDF inhibited cell viability, and induced oxidative stress and DNA damage in lymphocytes. In addition, results indicate that EDF induced apoptosis in lymphocytes concurrent with ROS generation, loss of mitochondrial membrane potential, up-regulation of Bax and caspase-9/-3 activation. Mechanistically, incubation of lymphocytes with N-acetylcysteine (ROS scavenger) abrogated the ROS generation and apoptosis caused by EDF. These findings suggest that ROS generation by EDF acts as an upstream signal leading to DNA damage and apoptosis in lymphocytes. This study also showed that apigenin could potentially attenuate EDF-induced oxidative stress, DNA damage and apoptosis in lymphocytes. Collectively, these results suggest that EDF exerts cytotoxicity and DNA damage in lymphocytes, and apigenin could be a potent dietary anti-oxidant regimen against EDF-induced toxicity on human health.

摘要

敌敌畏(EDF)是一种有机磷农药,用于农业害虫防治。然而,已经证明 EDF 会在农产品中积累,对人类健康造成危害。尽管有关于 EDF 对环境影响的报告,但 EDF 对人体细胞系统特别是免疫细胞的毒性作用尚未阐明。在这项研究中,研究了 EDF 对人外周血淋巴细胞的遗传毒性和细胞毒性及其通过芹菜素(膳食类黄酮)的改善作用。我们证明 EDF 抑制细胞活力,并在淋巴细胞中诱导氧化应激和 DNA 损伤。此外,结果表明 EDF 诱导淋巴细胞凋亡伴随着 ROS 的产生、线粒体膜电位的丧失、Bax 的上调和 caspase-9/-3 的激活。在机制上,用 N-乙酰半胱氨酸(ROS 清除剂)孵育淋巴细胞可消除 EDF 引起的 ROS 产生和凋亡。这些发现表明,EDF 产生的 ROS 作为一种上游信号,导致淋巴细胞中的 DNA 损伤和凋亡。这项研究还表明,芹菜素可能潜在地减轻 EDF 诱导的淋巴细胞中的氧化应激、DNA 损伤和凋亡。总之,这些结果表明 EDF 在淋巴细胞中具有细胞毒性和 DNA 损伤作用,而芹菜素可能是一种有效的膳食抗氧化剂方案,可对抗 EDF 对人类健康的毒性。

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