Comparative Evaluation of the Preventive Effects of Citral, Silymarin, Thymoquinone, and Curcumin on 5-Fluorouracil-Induced Cardiac and Pulmonary Toxicity in Rats.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: 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.