Abstract
BACKGROUND: Doxorubicin (DOX) is used to treat various types of cancers. However, its use is restricted by cardiotoxicity, a leading cause of morbidity and mortality. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) may be associated with cardioprotective properties. PURPOSE: This study aims to determine the protective effects of different semaglutide (SEM) doses on DOX-induced cardiotoxicity in a rat model. METHODOLOGY: Thirty-five female Wistar rats were divided into five groups. The first group received distilled water as a negative control (NC); the positive control (PC) group received distilled water plus DOX; the third group (SL) received a low dose of SEM (0.06 mg/kg) plus DOX; the fourth group (SM) received a moderate dose of SEM (0.12 mg/kg) plus DOX; and the fifth group (SH) received a high dose of SEM (0.24 mg/kg) plus DOX. Blood samples were collected on day 8 to assess serum troponin, lactate dehydrogenase (LDH), creatine phosphokinase (CPK), total lipid profile, and vascular cell adhesion molecule 1 (VCAM-1). Cardiac tissue was sent for histopathological analysis. RESULTS: DOX increased the total cholesterol (TC), low-density lipoprotein (LDL), triglyceride (TG), LDH, and CKP levels. Moderate and high doses of semaglutide significantly reduced serum cholesterol levels (*p = 0.0199), (**p = 0.0077), respectively. A significant reduction (***p = 0.0013) in total body weight after treatment with SEM was observed in the SL group and a highly significant reduction (****p < 0.0001) was observed in the SM and SH groups. SEM at all doses reduced CPK levels. The SL group showed a significant reduction in troponin level (*p=0.0344). Serum LDH levels were reduced by all three SEM doses. The histopathological findings support the biochemical results. CONCLUSION: Semaglutide may possess cardioprotective properties against DOX-induced cardiotoxicity in a rat model by decreasing serum biochemical markers of cardiotoxicity.