Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, İbrahim Çeçen University of Ağrı, Ağrı, Turkey.
Department of Biochemistry, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey.
Biomed Pharmacother. 2018 Oct;106:443-453. doi: 10.1016/j.biopha.2018.06.161. Epub 2018 Jul 11.
Doxorubicin (DOX) is an effective antineoplastic agent of the anthracycline group. However, as with most anticancer drugs, they cause some toxic effects, including major cardiotoxicity and cognitive impairment. In this study, protective effects of morin against DOX-induced cardiotoxicity and neurotoxicity in rats were investigated. Morin was orally administered to rats at a dose of 50 and 100 mg/kg body weight for 10 days. DOX was administered 40 mg/kg body weight by single dose intraperitoneal injection on the 8th day of the study. Both the levels of glutathione (GSH) and malondialdehyde (MDA) were assessed and enzyme activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were assessed to determine the protective effect of morin against oxidative stress. To determine the anti-inflammatory effect, the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), nuclear factor kappa B (NF-κB) were assessed in the heart and brain tissues. Lactate dehydrogenase (LDH) and creatine kinase isoenzyme-MB (CKMB) activities, which are cardiac function markers, and cardiac troponin-I (cTn-I) levels were also determined. Anti-apoptotic effect was determined by anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) and pro-apoptotic protein cysteine aspartate specific protease-3 (caspase-3) changes. The regulatory role of morin in signal transduction in the brain tissue was assigned with the determination of amount of acetylcholinesterase (AChE), and its healing effect on the central nervous system was determined with imuinohistochemical detection of glial fibrillar acidic protein (GFAP) level. Histopathological evaluation of heart and brain tissues was performed in all groups.
多柔比星（DOX）是蒽环类抗肿瘤药物中的一种有效药物。然而，与大多数抗癌药物一样，它们会引起一些毒性作用，包括严重的心脏毒性和认知障碍。在这项研究中，研究了桑色素对大鼠多柔比星诱导的心脏毒性和神经毒性的保护作用。桑色素以 50 和 100mg/kg 体重的剂量口服给予大鼠，连续 10 天。在研究的第 8 天，通过单次腹腔注射给予 DOX，剂量为 40mg/kg 体重。评估谷胱甘肽（GSH）和丙二醛（MDA）的水平，并评估超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx）的酶活性，以确定桑色素对氧化应激的保护作用。为了确定抗炎作用，评估心脏和脑组织中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、核因子 kappa B（NF-κB）的水平。还测定了乳酸脱氢酶（LDH）和肌酸激酶同工酶-MB（CKMB）的活性，这些是心脏功能标志物，以及心肌肌钙蛋白-I（cTn-I）的水平。通过 B 细胞淋巴瘤-2（Bcl-2）和半胱天冬氨酸特异性蛋白酶-3（caspase-3）变化来确定抗凋亡作用。通过测定乙酰胆碱酯酶（AChE）的量来确定桑色素在脑组织信号转导中的调节作用，并通过胶质纤维酸性蛋白（GFAP）水平的免疫组织化学检测来确定其对中枢神经系统的治疗作用。对所有组的心脏和脑组织进行组织病理学评估。
