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Hepatoprotective effect of arjunolic acid against cisplatin‐induced hepatotoxicity: Targeting oxidative stress, inflammation, and apoptosis
Journal of Biochemical and Molecular Toxicology ( IF 3.2 ) Pub Date : 2021-01-25 , DOI: 10.1002/jbt.22714
Iman O Sherif 1
Affiliation  

Minimizing the adverse effects of chemotherapeutic agents remains a therapeutic challenge. Cisplatin (CP) induces hepatotoxicity through activation of oxidative stress, inflammation, and apoptosis cascades which is considered a significant drawback. Thus, this study aimed to highlight the possible hepatoprotective role of arjunolic acid (Arj) in a rat model of CP‐induced hepatotoxicity. Four groups of rats were included; the normal control group, Arj control group, CP group which was injected with 7.5 mg/kg CP intraperitoneally to induce hepatotoxicity, and the treated group (Arj + CP), which was orally administered 20 mg/kg Arj for 10 days with a CP hepatotoxic dose on day 5. Blood and liver tissues were assembled for analysis at the end of the study. Pretreatment with Arj exhibited a marked improvement in liver function as well as histopathology when compared with the CP group. Moreover, Arj suppressed the oxidative stress in hepatic tissue by significantly decreasing malondialdehyde and nitric oxide contents along with markedly elevating the levels of superoxide dismutase, catalase, and reduced glutathione when compared with CP injected rats. Attenuation of hepatic inflammation and apoptosis was also reported with Arj treatment through the marked reduction in the proinflammatory cytokine tumor necrosis factor α level as well as the apoptotic marker caspase‐3 protein expression in comparison to the CP group. This study explored for the first time the Arj hepatoprotective effect against CP‐induced hepatotoxicity through its antioxidant, anti‐inflammatory, and antiapoptotic activities.

中文翻译:

芥酸对顺铂诱导的肝毒性的肝保护作用:针对氧化应激,炎症和细胞凋亡

使化学治疗剂的副作用最小化仍然是治疗上的挑战。顺铂(CP)通过激活氧化应激,炎症和凋亡级联反应诱导肝毒性,这被认为是一个重大缺陷。因此,本研究旨在强调在CP诱导的肝毒性大鼠模型中,阿魏酸(Arj)可能具有保肝作用。包括四组大鼠。正常对照组,Arj对照组,腹膜内注射7.5 mg / kg CP引起肝毒性的CP组和治疗组(Arj + CP),口服CP口服20 mg / kg Arj 10天在第5天给予肝毒性剂量。在研究结束时,收集血液和肝组织进行分析。与CP组相比,用Arj进行的预处理显示出肝功能和组织病理学的显着改善。此外,与注射CP的大鼠相比,Arj通过显着降低丙二醛和一氧化氮含量以及显着提高超氧化物歧化酶,过氧化氢酶水平和减少谷胱甘肽水平来抑制肝组织的氧化应激。与CP组相比,Arj治疗还报告了肝脏炎症和细胞凋亡的减轻,这是由于促炎性细胞因子肿瘤坏死因子α水平的显着降低以及凋亡标志物caspase-3蛋白表达的降低。这项研究首次探索了Arj通过其抗氧化,抗炎和抗凋亡活性对CP诱导的肝毒性的肝保护作用。
更新日期:2021-01-25
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