Zahed Tohid, Ahmadi Nasrollah, Noorbakhsh Mohammad Foad, Saeed Nazifi, Ahmad Oryan
Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.
Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.
J Pharmacopuncture. 2024 Dec 31;27(4):277-286. doi: 10.3831/KPI.2024.27.4.277.
5-fluorouracil chemotherapy is a highly recommended treatment for different types of solid tumors. However, this treatment can have severe side effects on the heart and lungs. In this study, we compared the protective effects of citral, silymarin, thymoquinone, and curcumin against 5-fluorouracil-induced toxicity in the heart and lungs of rats.
56 healthy adult male rats were randomly assigned to seven experimental groups (n = 8), including healthy and carrier (dimethylsulfoxide) groups, 5-fluorouracil, citral group, silymarin group, thymoquinone group, and curcumin group. Blood samples and representative tissue specimens of the heart and lungs were immediately collected at the end of the experiment to measure the biochemical parameters, conduct histopathological studies, and analyze antioxidant activity, respectively.
The intraperitoneal administration of 5-fluorouracil caused cardiotoxicity, as evidenced by elevated serum levels of creatine phosphokinase, creatine kinase-MB (p < 0.05), and lactate dehydrogenase (p < 0.05). Besides, 5-fluorouracil increased malondealdehyde levels, indicating a lipid peroxidation index and a decrease in the total antioxidant capacity index in the cardiac and pulmonary tissues (p < 0.05) of the animals. The preventive and therapeutic use of all the above compounds, in combination with 5-fluorouracil, led to a decrease in the mentioned cardiac serum biomarkers and malondealdehyde in the animals (p < 0.05). In addition, all the therapeutic compounds increased total antioxidant capacity in the heart and lungs (p < 0.05), indicating a high antioxidant capacity of these biological substances in ameliorating the resultant oxidative and histologic damages.
Our study indicated that the natural compounds citral, silymarin, thymoquinone, and curcumin, when combined with 5-fluorouracil, could minimize the histopathological and biochemical changes caused by 5-fluorouracil treatment in the heart and pulmonary tissues likely via antioxidant mechanisms. These products can be useful and effective in chemotherapy patients by reducing the potential adverse effects of 5-fluorouracil administration.
5-氟尿嘧啶化疗是针对不同类型实体瘤的一种高度推荐的治疗方法。然而，这种治疗可能会对心脏和肺部产生严重的副作用。在本研究中，我们比较了柠檬醛、水飞蓟宾、百里醌和姜黄素对5-氟尿嘧啶诱导的大鼠心脏和肺部毒性的保护作用。
56只健康成年雄性大鼠被随机分为7个实验组（n = 8），包括健康组和载体（二甲基亚砜）组、5-氟尿嘧啶组、柠檬醛组、水飞蓟宾组、百里醌组和姜黄素组。在实验结束时立即采集血液样本以及心脏和肺部的代表性组织标本，分别用于测量生化参数、进行组织病理学研究以及分析抗氧化活性。
腹腔注射5-氟尿嘧啶导致心脏毒性，血清肌酸磷酸激酶、肌酸激酶-MB（p < 0.05）和乳酸脱氢酶水平升高（p < 0.05）可证明这一点。此外，5-氟尿嘧啶增加了丙二醛水平，表明脂质过氧化指数升高，并且动物心脏和肺部组织中的总抗氧化能力指数降低（p < 0.05）。上述所有化合物与5-氟尿嘧啶联合进行预防性和治疗性使用，导致动物体内上述心脏血清生物标志物和丙二醛水平降低（p < 0.05）。此外，所有治疗性化合物均增加了心脏和肺部的总抗氧化能力（p < 0.05），表明这些生物物质在改善由此产生的氧化和组织学损伤方面具有高抗氧化能力。
我们的研究表明，天然化合物柠檬醛、水飞蓟宾、百里醌和姜黄素与5-氟尿嘧啶联合使用时，可能通过抗氧化机制将5-氟尿嘧啶治疗引起的心脏和肺部组织的组织病理学和生化变化降至最低。这些产品通过减少5-氟尿嘧啶给药的潜在不良反应，对化疗患者可能是有用且有效的。
