Potential Cardioprotective effect of Scopoletin on Dox-triggered Cardiotoxic effect in Rodents

Abstract

Doxorubicin is a chemotherapeutic drug commonly employed in cancer treatment., renowned for its efficacy in destroying cancer cells. However, it is also associated with cardiotoxicity, which leads to damage in heart muscle cells (cardiomyocytes). A total of fifty-five adult rats were utilized and categorized divided into four separate groups for the study: To evaluate the overall health and potential cardiac impacts, we measured BW, heart weight, and Electrocardiogram (ECG) measurements. Serum levels of cardiac troponin-I were assessed to gauge heart muscle damage and cardiotoxicity. Additionally, serum malondialdehyde (MDA) levels were analyzed to determine lipid peroxidation, a sign of oxidative stress. Total serum antioxidant capacity (TAC) was also measured to assess the body's overall antioxidant defense. Furthermore, histopathological examination of heart tissue samples was conducted under a microscope to identify any structural or cellular damage resulting from the treatments. In the DOX group, notable alterations in ECG parameters were observed, signaling cardiac impairment. Additionally, there was a noteworthy rise in serum cardiac troponin-I level (P < 0.001), indicating damage to heart muscle. Serum malondialdehyde (MDA) levels, a marker of oxidative stress, also increased markedly (P < 0.001). In contrast, TAC showed a noteworthy decline (P < 0.001), suggesting diminished antioxidant defenses. Histopathological examination with haematoxylin and eosin staining revealed signs of cardiomyopathy, including structural abnormalities in the heart tissue. Furthermore, the apoptotic index, assessed through caspase-3 staining, was significantly higher (P < 0.001), reflecting increased cell death in the heart comparingwith the control group. Conversely, the animal group pre-treatment with scopoletin (SPT) exhibited noteworthy improvements. ECG parameters showed reduced signs of cardiac dysfunction, suggesting enhanced cardiac health. Levels of serum trponin (P < 0.001) and malondialdehyde (P < 0.001) were notably lower, indicating decreased heart muscle damage and oxidative stress. The TAC levels increased significantly (P < 0.001), reflecting improved antioxidant defenses. Histopathological analysis revealed better preservation of heart tissue structure with fewer abnormalities. Additionally, the apoptotic index was significantly lower (P < 0.001), suggesting reduced cell death in cardiac tissue comparing to doxorubicin group.