Cardioprotective Effect of Enalapril and Hesperidin against 5-Fluoro Uracil Induced Myocardial Toxicity in Rats
DOI:
https://doi.org/10.47957/ijciar.v8i2.199Keywords:
Myocardial toxicity, C-reactive protein, Flavonoid, Cardiac troponin, Oxidative stressAbstract
Various solid malignancies, especially those affecting the gastrointestinal tract and carcinoma of the breast, receive a wide use of the drug 5-fluorouracil in their treatment as an element of oncological practice. The secondary commonest adverse outcome linked to the cytostatic agents is cardiotoxicity and 5-fluorouracil is involved in about 7 percent of the cases. This paper explores the protective effects of the angiotensin-converting-enzyme inhibitor enalapril, in addition to arteriolar relaxation drug hedperidin against 5-fluorouracil triggered myocardial damage in Wistar rats. Thirty adult rats were randomly divided to five sets and used as a control group (Group I) that received normal saline (10 mg/kg), 5-fluorouracil-only group (Group II), enalapril-only group (Group III), hesperidin-only group (Group IV) and a combination of enalapril and hesperidin group (Group V). 5-fluorouracil administration started at Day 10 of the protocol, and except the control group, all others received 5-fluorouracil treatment on consecutive days At day 14, every cohort was sacrificed and blood specimens as well as the heart tissues were collected to be tested biochemically. Myocardial Toxicity depicted itself through increase of cardiac enzymes (cardiac troponin, creatine kinase-MB, lactate dehydrogenase) and increase of nitric oxide, endothelin-1 and cytokines interleukin-1, interleukin-8 and tumour necrosis factor-alpha. In connection with these alterations, there were augmented levels of serum lipid parameters, such as triglycerides, total cholesterol, low-density lipoprotein, and very-low-density lipoprotein than the base rates, and low levels of high-density lipoprotein. In parallel to the changes in metabolism were reduced antioxidant defences as suggested by reduced superoxide dismutase, catalase and glutathione peroxidase, activities whereas the levels of malondialdehyde increased. Monotherapy with enalapril and hesperidin did not affect mortality or biomarkers, but when used together they were able to alleviate 5-fluorouracil-induced cardiotoxicity, especially by preventing oxidative stress, myocardial necrosis, lipid peroxidation and cytokine production as well as enhancing antioxidant activity. Concisely, the findings indicate that the combination of enalapril and hesperidin has a synergistic protective mechanism on 5-fluorouracil cardiotoxicity.
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