Alsirhani Alaa Muqbil, Abu-Almakarem Amal S, Alwaili Maha Abdullah, Aljohani Salwa, Alali Ibtisam, AlRashidi Aljazi Abdullah, Abuzinadah Najlaa Yousef, Alkhodair Sahar Abdulrahman, Mobasher Maysa A, Alothaim Tahiyat, Eid Thamir M, El-Said Karim Samy
Department of Chemistry, College of Science, Jouf University, Sakaka 72341, Saudi Arabia.
Department of Basic Medical Sciences, Faculty of Applied Medical Sciences, Al-Baha University, Al Baha 65431, Saudi Arabia.
Int J Mol Sci. 2024 Nov 22;25(23):12541. doi: 10.3390/ijms252312541.
Doxorubicin (DOX), an anticancer drug, is used to treat several types of tumors, but it has detrimental side effects that restrict its therapeutic efficacy. One is the iron-dependent form of ferroptosis, which is characterized by elevated ROS production and iron overload. has a diverse range of biological and pharmaceutical actions due to their antioxidant properties. This study investigated the effect of extract (SAE) on hepatotoxicity caused by DOX in rats. Phytochemical analysis was performed to assess compounds in SAE. The ADMETlab 2.0 web server was used to predict the pharmacokinetic properties of the most active components of SAE when DOX was injected into rats. Molecular docking studies were performed using AutoDock Vina. Forty male Sprague Dawley rats were divided into four groups of ten rats each (G1 was a negative control group, G2 was given 1/10 of SAE LD by oral gavage (340 mg/kg), G3 was given 4 mg/kg of DOX intraperitoneally (i.p.) once a week for a month, and G4 was administered DOX as in G3 and SAE as in G2). After a month, biochemical and histopathological investigations were performed. Rats given SAE had promising levels of phytochemicals, which could significantly ameliorate DOX-induced hepatotoxicity by restoring biochemical alterations, mitigating ferroptosis, and upregulating the NRF-2-SLC7A-11-GPX-4 signaling pathway. These findings suggest that SAE could potentially alleviate DOX-induced hepatotoxicity in rats.
阿霉素（DOX）是一种抗癌药物，用于治疗多种类型的肿瘤，但其有害的副作用限制了其治疗效果。其中之一是铁依赖性的铁死亡形式，其特征是活性氧生成增加和铁过载。由于其抗氧化特性，具有多种生物和药理作用。本研究调查了 提取物（SAE）对阿霉素诱导的大鼠肝毒性的影响。进行了植物化学分析以评估SAE中的化合物。当将阿霉素注射到大鼠体内时，使用ADMETlab 2.0网络服务器预测SAE最活跃成分的药代动力学特性。使用AutoDock Vina进行分子对接研究。将40只雄性Sprague Dawley大鼠分为四组，每组10只（G1为阴性对照组，G2通过口服灌胃给予1/10的SAE半数致死量（340mg/kg），G3每周一次腹腔注射（i.p.）4mg/kg阿霉素，持续一个月，G4按G3给予阿霉素，按G2给予SAE）。一个月后，进行了生化和组织病理学检查。给予SAE的大鼠具有良好的植物化学物质水平，通过恢复生化改变、减轻铁死亡和上调NRF-2-SLC7A-11-GPX-4信号通路，可显著改善阿霉素诱导的肝毒性。这些发现表明，SAE可能潜在地减轻大鼠阿霉素诱导的肝毒性。
