Dose-Dependent Cardiovascular Effects of Semaglutide in a Rat Model of Doxorubicin-Induced Cardiac Injury: An Integrated Experimental and Computational Study
Abstract
Background: Doxorubicin is a widely used anthracycline, but dose-dependent cardiotoxicity limits its clinical use, and few preventive options exist. Semaglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, shows cardiovascular benefits in clinical and preclinical studies, yet its effect on doxorubicin-induced cardiac injury is not fully defined.
Objectives: To evaluate the cardiovascular safety and protective potential of semaglutide against doxorubicin-induced cardiotoxicity in Wistar albino rats.
Methodology: Male Wistar albino rats are randomly allocated to five groups (n = 6): negative control; positive control (single intraperitoneal doxorubicin dose of 12 mg/kg on day 7); and three groups receiving semaglutide at 0.06, 0.12, or 0.24 mg/kg for 7 days before doxorubicin. On day 8, cardiac injury is assessed by serum troponin, creatine kinase-MB and lactate dehydrogenase; oxidative-stress markers (malondialdehyde, glutathione, superoxide dismutase, catalase); inflammatory markers (tumor necrosis factor-α, interleukin-6); lipid profile; relative heart weight; electrocardiography; and cardiac histopathology. In-silico docking and ADMET screening complement the in-vivo work.
Results: At the end of the experimental period, the cardiovascular safety profile of semaglutide will be evaluated by assessment of general clinical observations, body weight, cardiovascular parameters, serum cardiac biomarkers, lipid profile, oxidative stress and inflammatory markers, relative heart weight, and cardiac histopathology. Serum troponin, CK-MB, and LDH will be used as important biochemical indicators of myocardial injury. Histopathological examination of cardiac tissue will be performed to identify myocardial degeneration, necrosis, inflammatory infiltration, edema, and vascular changes. The findings obtained from biochemical, functional, and histopathological investigations will be correlated to determine whether semaglutide produces any significant cardiovascular toxicity in Wistar rats.
Conclusions: Integrating biochemical, functional, structural, and computational evidence gives a comprehensive assessment of whether semaglutide protects against, or contributes to, cardiac injury under the experimental conditions used.
