Sandamali Jayasinghe A N, Hewawasam Ruwani P, Jayatilaka Kamani A P W, Mudduwa Lakmini K B
Department of Medical Laboratory Science, Faculty of Allied Health Sciences, University of Ruhuna, Galle 80000, Sri Lanka.
Department of Biochemistry, Faculty of Medicine, University of Ruhuna, Galle 80000, Sri Lanka.
Evid Based Complement Alternat Med. 2020 Apr 5;2020:6023737. doi: 10.1155/2020/6023737. eCollection 2020.
Dose-dependent cardiotoxicity of doxorubicin may lead to irreversible congestive heart failure. Although multiple mechanisms are involved, generation of free radicals is the most commonly postulated mechanism. Therefore, free radical scavengers are considered as potential therapeutic agents. As leaves are a rich source of flavonoids and phenols, they have the ability to scavenge free radicals effectively. Therefore, the objective of this study was to investigate the cardioprotective potential of leaf extract against doxorubicin-induced cardiotoxicity in rats. Rats were randomly divided into five groups with 10 animals in each group. Doxorubicin was administered intraperitonially at 18 mg/kg while lyophilized plant extract was administered orally at 2 g/kg. Dexrazoxane, at 180 mg/kg, was used as the positive control. Cardiac damage of doxorubicin control was evident with a significant increase ( < 0.05) in cardiac troponin I, NT-pro BNP, AST, and LDH compared to the normal control. Plant-treated group showed cardioprotective effect by significantly reducing ( < 0.05) all of the above parameters compared to doxorubicin control ( < 0.05). Increased oxidative stress in doxorubicin control was evident with a significant reduction in reduced glutathione, glutathione reductase, glutathione peroxidase, total antioxidant capacity, superoxide dismutase, and catalase activity and a significant increase in lipid peroxidation compared to the control. Interestingly, treatment with leaf extract showed a significant increase in all of the above antioxidant parameters and a significant reduction in lipid peroxidation by showing an antioxidant effect. A significant increase in myeloperoxidase activity confirmed the increased inflammatory activity in doxorubicin control group whereas plant-treated group showed a significant reduction ( < 0.05) which expressed the anti-inflammatory effect of leaf extract. Doxorubicin-treated group showed histological evidence of extensive damage to the myocardium while plant-treated group showed a preserved myocardium with lesser degree of damage. Pretreatment with leaf extract may replenish cardiomyocytes with antioxidants and promote the defense against doxorubicin-induced cardiotoxicity.
阿霉素的剂量依赖性心脏毒性可能导致不可逆的充血性心力衰竭。虽然涉及多种机制，但自由基的产生是最常被假定的机制。因此，自由基清除剂被认为是潜在的治疗药物。由于[植物名称]叶富含黄酮类化合物和酚类，它们具有有效清除自由基的能力。因此，本研究的目的是探讨[植物名称]叶提取物对阿霉素诱导的大鼠心脏毒性的心脏保护潜力。大鼠随机分为五组，每组10只动物。阿霉素腹腔注射剂量为18mg/kg，冻干植物提取物口服剂量为2g/kg。180mg/kg的右丙亚胺用作阳性对照。与正常对照组相比，阿霉素对照组的心脏损伤明显，心肌肌钙蛋白I、N末端脑钠肽前体、谷草转氨酶和乳酸脱氢酶显著升高（P<0.05）。与阿霉素对照组相比，植物治疗组通过显著降低（P<0.05）上述所有参数显示出心脏保护作用（P<0.05）。与对照组相比，阿霉素对照组氧化应激增加，还原型谷胱甘肽、谷胱甘肽还原酶、谷胱甘肽过氧化物酶、总抗氧化能力、超氧化物歧化酶和过氧化氢酶活性显著降低，脂质过氧化显著增加。有趣的是，[植物名称]叶提取物处理显示上述所有抗氧化参数显著增加，脂质过氧化显著降低，表现出抗氧化作用。髓过氧化物酶活性显著增加证实了阿霉素对照组炎症活性增加，而植物治疗组显著降低（P<0.05），这表明了[植物名称]叶提取物的抗炎作用。阿霉素治疗组显示出心肌广泛损伤的组织学证据，而植物治疗组显示心肌保存，损伤程度较轻。[植物名称]叶提取物预处理可能用抗氧化剂补充心肌细胞，并促进对阿霉素诱导的心脏毒性的防御。
