Department of Pharmacology and Therapeutics, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Ilorin, Kwara State, Nigeria.
Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Clinical Sciences, Lagos State University College of Medicine, 1-5 Oba Akinjobi Way, G.R.A., Ikeja, Lagos State, Nigeria.
Oxid Med Cell Longev. 2020 Oct 22;2020:1602816. doi: 10.1155/2020/1602816. eCollection 2020.
Cardiotoxicity as an off-target effect of doxorubicin therapy is a major limiting factor for its clinical use as a choice cytotoxic agent. Seeds of have been reported to possess both nutritional and medicinal values which include antidiabetic, weight losing, antihyperlipidemic, and antioxidative effects. Protective effects of ethanol seed extract () was investigated in doxorubicin (DOX)-mediated cardiotoxicity induced with single intraperitoneal injection of 15 mg/kg of DOX following the oral pretreatments of Wistar rats with 100-400 mg/kg/day of for 10 days, using serum cardiac enzyme markers (cardiac troponin I (cTI) and lactate dehydrogenase (LDH)), cardiac tissue oxidative stress markers (catalase (CAT), malonyldialdehyde (MDA), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione peroxidase (GSH-Px), and reduced glutathione (GSH)), and cardiac histopathology endpoints. In addition, both qualitative and quantitative analyses to determine IGESE's secondary metabolites profile and its antioxidant activities were also conducted. Results revealed that serum cTnI and LDH were significantly elevated by the DOX treatment. Similarly, activities of tissue SOD, CAT, GST, and GSH levels were profoundly reduced, while GPx activity and MDA levels were profoundly increased by DOX treatment. These biochemical changes were associated with microthrombi formation in the DOX-treated cardiac tissues on histological examination. However, oral pretreatments with 100-400 mg/kg/day of dissolved in 5% DMSO in distilled water significantly attenuated increases in the serum cTnI and LDH, prevented significant alterations in the serum lipid profile and the tissue activities and levels of oxidative stress markers while improving cardiovascular disease risk indices and DOX-induced histopathological lesions. The antioxidant studies showed to have good antioxidant profile and contained 56 major secondary metabolites prominent among which are -sitosterol, Phytol, neophytadiene, stigmasterol, vitamin E, hexadecanoic acid and its ethyl ester, Phytyl palmitate, campesterol, lupeol, and squalene. Overall, both the and findings indicate that may be a promising prophylactic cardioprotective agent against DOX-induced cardiotoxicity, at least in part mediated via 's antioxidant and free radical scavenging and antithrombotic mechanisms.
多柔比星治疗的心脏毒性是其作为细胞毒药物临床应用的主要限制因素。已经报道称，种子具有营养和药用价值，包括抗糖尿病、减肥、抗高血脂和抗氧化作用。用 15mg/kg 多柔比星（DOX）单次腹腔注射诱导 Wistar 大鼠心肌毒性，用 100-400mg/kg/天的 乙醇种子提取物（）进行口服预处理 10 天，研究 对 DOX 诱导的心脏毒性的保护作用，用血清心脏酶标志物（心肌肌钙蛋白 I（cTI）和乳酸脱氢酶（LDH））、心脏组织氧化应激标志物（过氧化氢酶（CAT）、丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽-S-转移酶（GST）、谷胱甘肽过氧化物酶（GSH-Px）和还原型谷胱甘肽（GSH））和心脏组织病理学终点。此外，还进行了定性和定量分析，以确定 IGESE 的次级代谢产物谱及其抗氧化活性。结果表明，DOX 处理显著升高了血清 cTnI 和 LDH。同样，组织 SOD、CAT、GST 和 GSH 水平的活性显著降低，而 GPx 活性和 MDA 水平显著增加。这些生化变化与 DOX 处理的心脏组织中的微血栓形成有关。然而，用 100-400mg/kg/天溶解在 5% DMSO 中的 预处理显著减轻了血清 cTnI 和 LDH 的升高，防止了血清脂质谱和组织氧化应激标志物的显著改变，同时改善了心血管疾病风险指数和 DOX 诱导的组织病理学损伤。抗氧化研究表明具有良好的抗氧化谱，含有 56 种主要的次级代谢产物，其中突出的是β-谷甾醇、植醇、新 Phytadiene、豆甾醇、生育酚、十六烷酸及其乙酯、叶绿醇棕榈酸酯、菜油甾醇、羽扇豆醇和角鲨烯。总之，和结果表明，可能是一种有前途的预防 DOX 诱导的心脏毒性的心脏保护剂，至少部分通过其抗氧化和自由基清除和抗血栓形成机制介导。
