Sherif Iman O
Emergency Hospital, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
J Biochem Mol Toxicol. 2021 Apr;35(4):e22714. doi: 10.1002/jbt.22714. Epub 2021 Jan 25.
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.
将化疗药物的不良反应降至最低仍然是一项治疗挑战。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，本研究旨在突出阿朱诺酸（Arj）在CP诱导的肝毒性大鼠模型中可能的肝保护作用。实验纳入了四组大鼠；正常对照组、Arj对照组、腹腔注射7.5mg/kg CP以诱导肝毒性的CP组，以及治疗组（Arj+CP），该组在第5天给予CP肝毒性剂量的同时口服20mg/kg Arj，持续10天。在研究结束时采集血液和肝脏组织进行分析。与CP组相比，Arj预处理在肝功能以及组织病理学方面均表现出显著改善。此外，与注射CP的大鼠相比，Arj通过显著降低丙二醛和一氧化氮含量以及显著提高超氧化物歧化酶、过氧化氢酶和还原型谷胱甘肽水平，抑制了肝组织中的氧化应激。与CP组相比，Arj治疗还通过显著降低促炎细胞因子肿瘤坏死因子α水平以及凋亡标志物半胱天冬酶-3蛋白表达，减轻了肝脏炎症和凋亡。本研究首次探讨了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。
