Ameliorative effects of betaine on cisplatin-induced cardiotoxicity in rats through anti-inflammatory pathways

Cisplatin (CS) is a broad-spectrum chemotherapeutic agent that causes serious adverse effects, such as cardiotoxicity, despite its potent anti-tumor efficacy. This study aimed to evaluate the cardioprotective effects of betaine in rats exposed to repeated low-dose CS administration using histopathological and immunohistochemical methods. Forty female Wistar albino rats were divided into four groups, including control, betaine, CS, and CS + betaine. Betaine (250 mg kg^-1) was administered orally on a daily basis for four weeks, while CS (8.00 mg kg^-1) was administered intraperitoneally once a week for the same duration. Cardiomyocytes were then examined using histopathological and immunohistochemical methods. The data were analyzed using one-way analysis of variance and Tukey tests. Histopathological analysis revealed cardiomyocyte disorganization, myofibril loss, and increased eosinophilia in the CS group. Betaine treatment partially prevented CS-induced histological damage, contributing to the cardiac muscle structure preservation. Immunohistochemical analyses demonstrated a significant increase in transforming growth factor-beta and interferon gamma expressions in the CS group, whereas betaine administration reduced transforming growth factor-beta levels. Interleukin 6 expression was lower in the CS + betaine group compared to the CS group. No significant differences were observed between groups regarding Interleukin-1β expression. These findings suggest that betaine may have protective effects against CS-induced cardiotoxicity. Its anti-inflammatory properties appear to mitigate cardiomyocyte damage.