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辣木叶乙醇提取物影响 DNA 损伤信号通路,以保护肝脏组织免受钴诱导的大鼠细胞凋亡。

Moringa oleifera leaves ethanolic extract influences DNA damage signaling pathways to protect liver tissue from cobalt -triggered apoptosis in rats.

机构信息

Forensic Medicine and Toxicology Department, Faculty of Veterinary Medicine, Zagazig University, Egypt.

Forensic Medicine and Toxicology Department, Faculty of Veterinary Medicine, Zagazig University, Egypt.

出版信息

Ecotoxicol Environ Saf. 2020 Sep 1;200:110716. doi: 10.1016/j.ecoenv.2020.110716. Epub 2020 May 22.

DOI:10.1016/j.ecoenv.2020.110716
PMID:32450433
Abstract

This study assessed the potential of Moringa oleifera leaves ethanol extract (MLEE) in attenuating the detrimental effects of cobalt dichloride (CoCl) on rat liver. Forty rats were assigned to five equal groups: control group, MLEE-treated group, CoCl-treated group, prophylaxis co-treated group, and therapeutic co-treated group. The levels of Co, hepatic injury markers, total antioxidant capacity (TAC), and oxidative stress biomarkers (reactive oxygen species [ROS] and protein carbonyl [PC]) were evaluated. Comet assay was used to evaluate the extent of DNA damage. Further, the expression profile of DNA-damage effector genes was assayed by real-time quantitative polymerase chain reaction (qRT-PCR) analysis. Immunohistochemical analysis of heat shock protein (HSP-70) in hepatocytes was conducted. The results showed that the exposure of CoCl to rats resulted in declined TAC, elevated oxidative injury, and induced DNA damage markers. Upregulation of mRNA expression of tumor suppressor protein (P53), apoptosis inducing factor (AIF), and apoptotic peptidase activating factor 1 (Apaf-1) was observed. The immunostaining density of HSP-70 expression was found to be elevated. Thus, MLEE reduced the CoCl-induced genotoxicity by preventing CoCl-induced generation of ROS, and protected against ROS mediated-oxidative injury and DNA damage. Moreover, the expression of DNA damage effector genes was affected. Based on these results, we conclude that MLEE is more effective when administered as a prophylactic regimen with the exposure to CoCl.

摘要

本研究评估了辣木叶乙醇提取物(MLEE)减轻氯化钴(CoCl)对大鼠肝脏的有害影响的潜力。将 40 只大鼠分为五组:对照组、MLEE 处理组、CoCl 处理组、预防 Co 共处理组和治疗 Co 共处理组。评估了 Co 的水平、肝损伤标志物、总抗氧化能力(TAC)和氧化应激生物标志物(活性氧 [ROS]和蛋白质羰基 [PC])。彗星试验用于评估 DNA 损伤程度。此外,通过实时定量聚合酶链反应(qRT-PCR)分析测定 DNA 损伤效应基因的表达谱。通过免疫组织化学分析肝细胞中的热休克蛋白(HSP-70)。结果表明,CoCl 暴露于大鼠导致 TAC 下降,氧化损伤增加,并诱导 DNA 损伤标志物。观察到肿瘤抑制蛋白(P53)、凋亡诱导因子(AIF)和凋亡蛋白酶激活因子 1(Apaf-1)的 mRNA 表达上调。HSP-70 表达的免疫染色密度升高。因此,MLEE 通过防止 CoCl 诱导的 ROS 生成,减轻 CoCl 诱导的遗传毒性,防止 ROS 介导的氧化损伤和 DNA 损伤。此外,DNA 损伤效应基因的表达受到影响。基于这些结果,我们得出结论,MLEE 在接触 CoCl 时作为预防方案给药更有效。

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