Ali Yasmine A, Ahmed Osama M, Soliman Hanan A, Abdel-Gabbar Mohamed, Al-Dossari M, El-Gawaad N S Abd, El-Nahass El-Shaymaa, Ahmed Noha A
Biochemistry Department, Faculty of Science, Beni-Sued University, P.O. Box 62521, Beni-Suef, Egypt.
Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, P.O. Box 62521, Beni-Suef, Egypt.
Evid Based Complement Alternat Med. 2023 Feb 22;2023:5068304. doi: 10.1155/2023/5068304. eCollection 2023.
Paclitaxel is a primary chemotherapy agent that displays antitumor activity against a variety of solid tumors. However, the clinical effectiveness of the drug is hampered by its nephrotoxic and cardiotoxic side effects. Thus, this investigation aimed at assessing the protective effects of rutin, hesperidin, and their combination to alleviate nephrotoxicity caused by paclitaxel (Taxol), cardiotoxicity in male Wistar rats, as well as oxidative stress. Rutin (10 mg/kg body weight), hesperidin (10 mg/kg body weight), and their mixture were given orally every other day for six weeks. Rats received intraperitoneal injections of paclitaxel twice weekly, on the second and fifth days of the week, at a dose of 2 mg/kg body weight. In paclitaxel-treated rats, the treatment of rutin and hesperidin decreased the elevated serum levels of creatinine, urea, and uric acid, indicating a recovery of kidney functions. The cardiac dysfunction in paclitaxel-treated rats that got rutin and hesperidin treatment also diminished, as shown by a substantial reduction in elevated CK-MB and LDH activity. Following paclitaxel administration, the severity of the kidney and the heart's histopathological findings and lesion scores were markedly decreased by rutin and hesperidin administration. Moreover, these treatments significantly reduced renal and cardiac lipid peroxidation while markedly increased GSH content and SOD and GPx activities. Thus, paclitaxel likely induces toxicity in the kidney and the heart by producing oxidative stress. The treatments likely countered renal and cardiac dysfunction and histopathological changes by suppressing oxidative stress and augmenting the antioxidant defenses. Rutin and hesperidin combination was most efficacious in rescuing renal and cardiac function as well as histological integrity in paclitaxel-administered rats.
紫杉醇是一种主要的化疗药物，对多种实体瘤具有抗肿瘤活性。然而，该药物的临床疗效受到其肾毒性和心脏毒性副作用的阻碍。因此，本研究旨在评估芦丁、橙皮苷及其组合对减轻紫杉醇（泰素）引起的肾毒性、雄性Wistar大鼠心脏毒性以及氧化应激的保护作用。芦丁（10毫克/千克体重）、橙皮苷（10毫克/千克体重）及其混合物每隔一天口服给药六周。大鼠每周在第二和第五天接受两次腹腔注射紫杉醇，剂量为2毫克/千克体重。在接受紫杉醇治疗的大鼠中，芦丁和橙皮苷治疗降低了血清肌酐、尿素和尿酸水平的升高，表明肾功能有所恢复。接受芦丁和橙皮苷治疗的紫杉醇处理大鼠的心脏功能障碍也有所减轻，表现为CK-MB和LDH活性升高的显著降低。给予紫杉醇后，芦丁和橙皮苷给药显著降低了肾脏和心脏组织病理学发现的严重程度以及病变评分。此外，这些治疗显著降低了肾脏和心脏的脂质过氧化，同时显著增加了谷胱甘肽含量以及超氧化物歧化酶和谷胱甘肽过氧化物酶的活性。因此，紫杉醇可能通过产生氧化应激在肾脏和心脏中诱导毒性。这些治疗可能通过抑制氧化应激和增强抗氧化防御来对抗肾脏和心脏功能障碍以及组织病理学变化。芦丁和橙皮苷组合在挽救接受紫杉醇治疗大鼠的肾脏和心脏功能以及组织学完整性方面最为有效。
