Cancer Research and Molecular Biology Laboratories, University of Ibadan, Ibadan, Nigeria.
Nutrition and Industrial Biochemistry Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, University of Ibadan, Ibadan, Nigeria.
Toxicol Appl Pharmacol. 2021 Jan 15;411:115380. doi: 10.1016/j.taap.2020.115380. Epub 2020 Dec 24.
Doxorubicin (DOX), is a drug against lung malignancies with undesirable side effect including oxidative, inflammatory and apoptotic effects. Luteolin (LUT), present in fruits and vegetables is pharmacologically active against oxido-inflammatory and apoptotic responses. The present study examined the effect of LUT on DOX-induced lungs and blood dysfunction in Wistars rat (sex: male; 10 weeks old, 160 ± 5 g). Randomly grouped (n = 10) rats were treated as follows: control, LUT alone (100 mg/kg; per os), DOX (2 mg/kg; i. p), and co-treated rats with LUT (50 or 100 mg/kg) and DOX for two consecutive weeks. DOX alone adversely altered the final body and relative organ weights, red and white blood cell and platelet counts. DOX significantly (p > 0.05) reduced lungs antioxidant capacity, and anti-inflammatory cytokines; increased biomarkers of oxidative stress, caspase-3 activity, and pro-inflammatory cytokine. Morphological damages accompanied these biochemical alterations in the lung of experimental rats. Co-treatment with LUT, dose-dependently reversed DOX-mediated changes in rats' survival, toxic responses, and diminished oxidative stress in rat's lungs. Furthermore, co-treatment with LUT resulted in the reduction of pro-inflammatory cytokines and apoptotic biomarkers, increased red and white blood cell, platelet counts and abated pathological injuries in rat lungs treated with DOX alone. In essence, our findings indicate that LUT dose-dependently mitigated DOX-induced toxicities in the lungs and haematopoietic systems. Supplementation of patients on DOX-chemotherapy with phytochemicals exhibiting antioxidant activities, specifically LUT, could circumvent the onset of unintended toxic responses in the lungs and haematopoietic system exposed to DOX.
多柔比星（DOX）是一种治疗肺癌的药物，但具有氧化、炎症和凋亡等不良副作用。木樨草素（LUT）存在于水果和蔬菜中，具有对抗氧化炎症和凋亡反应的药理作用。本研究探讨了 LUT 对 Wistar 大鼠（性别：雄性；10 周龄，160±5g）多柔比星诱导的肺部和血液功能障碍的影响。将随机分组（n=10）的大鼠分别给予以下处理：对照组、LUT 单独（100mg/kg；口服）、DOX（2mg/kg；腹腔注射）以及 LUT（50 或 100mg/kg）和 DOX 连续两周联合治疗组。DOX 单独给药会导致终末体重和相对器官重量、红细胞和血小板计数降低。DOX 显著（p>0.05）降低了肺部抗氧化能力和抗炎细胞因子；增加了氧化应激标志物、caspase-3 活性和促炎细胞因子。形态学损伤伴随着这些生化改变发生在实验大鼠的肺部。LUT 联合治疗以剂量依赖性的方式逆转了 DOX 介导的大鼠存活、毒性反应的变化，并减轻了 DOX 对大鼠肺部的氧化应激。此外，LUT 联合治疗导致促炎细胞因子和凋亡生物标志物减少，红细胞和血小板计数增加，并减轻了单独用 DOX 处理大鼠肺部的病理损伤。总之，我们的研究结果表明，LUT 以剂量依赖的方式减轻了 DOX 对肺部和造血系统的毒性作用。在接受 DOX 化疗的患者中补充具有抗氧化活性的植物化学物质，特别是 LUT，可能会避免因 DOX 引起的肺部和造血系统的意外毒性反应的发生。
