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Abstract
5-Fluorouracil (5-FU) is one of the most common chemotherapeutic agents used in treating solid tumors, and the 5-FU-induced cardiotoxicity is the second cause of cardiotoxicity induced by chemotherapeutic drugs. Propolis (Pro) has vigorous anti-inflammatory activity. Its cardio-protective characteristic against doxorubicin-induced cardiotoxicity was previously proven. The current study aimed to appraise the effect of Pro on 5-FU-induced cardiotoxicity in rats. Twenty-four male Wistar rats were divided into four groups: Control, 5-FU, 5-FU + Pro 250 mg/kg, and 5-FU + Colchicine (CLC) 5 mg/kg. Different hematological, serological, biochemical, histopathological, and molecular assays were performed to assess the study’s aim. Moreover, a rat myocardium (H9C2(2–1)) cell line was also used to assess this protective effect in-vitro. 5-FU resulted in significant cardiotoxicity represented by an increase in malondialdehyde (MDA) levels, cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) expression, cardiac enzyme levels, and histopathological degenerations. 5-FU treatment also decreased bodyweight, total anti-oxidant capacity (TAC), catalase (CAT) levels, blood cell counts, and hemoglobin (Hb) levels. In addition, 5-FU disrupted ECG parameters, including increased elevation in the ST-segment and increased QRS complex and QTc duration. Treating with Pro reduced oxidative stress, cardiac enzymes, histopathological degenerations, and COX-2 expression in cardiac tissue alleviated ECG disturbances and increased the number of blood cells and TAC levels. Moreover, 5-FU-induced bodyweight loss was ameliorated after treatment with Pro. Our results demonstrated that treatment with Pro significantly improved cardiotoxicity induced by 5-FU in rats.
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1 Shahid Beheshti University of Medical Sciences, Student Research Committee, Virtual School of Medical Education and Management, Tehran, Iran (GRID:grid.411600.2); Tehran University of Medical Sciences, Students’ Scientific Research Center (SSRC), Tehran, Iran (GRID:grid.411705.6) (ISNI:0000 0001 0166 0922); Babol University of Medical Sciences, Student Research Committee, Babol, Iran (GRID:grid.411495.c) (ISNI:0000 0004 0421 4102)
2 Babol University of Medical Sciences, Student Research Committee, Babol, Iran (GRID:grid.411495.c) (ISNI:0000 0004 0421 4102)
3 Babol University of Medical Sciences, Cellular and Molecular Biology Research Center, Health Research Center, Babol, Iran (GRID:grid.411495.c) (ISNI:0000 0004 0421 4102)
4 University of Michigan, Division of Cardiovascular Medicine, Cardiac Arrhythmia Service, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370)
5 Mayo Clinic, Department of Radiation Oncology, Phoenix, USA (GRID:grid.470142.4) (ISNI:0000 0004 0443 9766)
6 Islamic Azad University, Department of Veterinary Parasitology, Babol-Branch, Babol, Iran (GRID:grid.467532.1) (ISNI:0000 0004 4912 2930)