en Cardiovascular Physiology/Pharmacology Cardiovascular Physiology/Pharmacology Experimental research article Experimental research article <p><span style="font-size:12px;"><span style="font-family:Arial;"><strong>Introduction: </strong>5-fluorouracil is commonly used for solid cancers, with cardiotoxicity being the main side effect. S-adenosylmethionine (SAMe) is known to have therapeutic benefits in several human diseases, including cancer, osteoarthritis, Alzheimer&rsquo;s disease, depression, and chronic liver diseases. SAMe also possesses cytoprotective and antioxidant properties. The present investigation aims to evaluate the effects of SAMe on 5-Fluorouracil-induced cardiotoxicity in rats by comparing it with a typical medication, Silymarin (SIL).<br /> <strong>Methods: </strong>Forty male albino rats were divided into five groups as follows: Control (D.W. only), 5-Fluorouracil (100 mg/kg), SAMe (100 mg/kg), 5-Fluorouracil 100 mg/kg+SAMe100 mg/kg, and 5-Fluorouracil 100 mg/kg+200 mg/kg SIL. Cardiotoxicity was induced with an intraperitoneal injection of a single dose of 5-Fluorouracil (100 mg/kg). Serum was collected, and histological analysis of the heart was performed to evaluate the rat model-5-FU&rsquo;s toxicity alone and in combination with SAMe and SIL. In addition to a heart histology examination, serum cardiac enzyme testing, pro-oxidant/antioxidant status, and cyclooxygenase-2 expression in cardiac tissue were examined.<br /> <strong>Results: </strong>5-Fluorouracil induced severe cardiotoxicity, as evidenced by increased histological deterioration, cardiac enzymes, cyclooxygenase-2 expression, and malondialdehyde concentrations. The overall antioxidant capacity was likewise reduced by 5-FU treatment. While oxidative stress, cardiac enzymes, histological degenerations, and cyclooxygenase-2 expression in cardiac tissue were reduced, total antioxidant capacity was improved by SAMe or SIL treatment.<br /> <strong>Conclusion: </strong>The cardiotoxicity induced by 5-fluorouracil in rats was ameliorated by SAMe or SIL therapy confirmed by reserved histological and biochemical analysis.</span></span></p> Antioxidant effect, Cardiotoxicity, Chemotherapy 315 322 http://ppj.phypha.ir/browse.php?a_code=A-10-2428-1&slc_lang=en&sid=1 Doha I. Alrawi doha.23php13@student.uomosul.edu.iq 3200319475328460038024 3200319475328460038024 No College of Pharmacy, University of Mosul, Mosul, Iraq Musab M. Khalaf musabph74@uomosul.edu.iq 3200319475328460038025 3200319475328460038025 No College of Pharmacy, University of Mosul, Mosul, Iraq Mohammed KJ. Alnori alnorimkj@uomosul.edu.iq 3200319475328460038026 000000018099054X Yes College of Pharmacy, University of Mosul, Mosul, Iraq