Abstract
Doxorubicin-induced cardiotoxicity is the leading cause of morbidity and mortality among cancer survivors. The present study was aimed to investigate the cardioprotective potential of methyl gallate; an active polyphenolic nutraceutical, against doxorubicin-induced cardiotoxicity in Wistar rats. Twenty-four female Wistar rats (150–200 g) were divided into four groups (n = 6) which consist of normal control (group I), doxorubicin control (group II), test-A (group III), and test-B (group IV). Group III and group IV animals were prophylactically treated with methyl gallate 150 mg/kg/day and 300 mg/kg/day orally, respectively, for seven days. Doxorubicin (25 mg/kg; single dose) was administered through an intraperitoneal route to group II, III, and IV animals on the seventh day to induce acute cardiotoxicity. On the 8th day, besides ECG analysis, serum CK, CK-MB, LDH, AST, MDA, and GSH were assayed. Following gross examination of isolated hearts, histopathological evaluation was performed by light microscopy. A significant (p < 0.05) cardiac injury, as well as oxidative stress, was observed in doxorubicin control rats in comparison to normal control rats. Methyl gallate at both the doses significantly (p < 0.05) reduced doxorubicin-induced ECG changes, dyslipidaemia, and elevation of CK, CK-MB, LDH, AST, MDA and increased GSH level. Methyl gallate reversed the doxorubicin-induced histopathological changes in the heart. The present study revealed that methyl gallate exerts cardioprotection against doxorubicin-induced cardiotoxicity in female Wistar rats by suppressing oxidative stress. Our study opens the perspective to clinical studies for consideration of methyl gallate as a potential chemoprotectant nutraceutical in the combination chemotherapy with doxorubicin to limit its cardiotoxicity.
Highlights
Cancer survival rates are significantly improving mainly due to the reflection over the past several decades of improved screening, diagnostic imaging, and improvement of therapeutic modalities in oncology
After randomization into different experimental groups, the rats were acclimatized to the laboratory conditions for one week before beginning the experiment. e experimental protocol was approved by the Institutional Animal Ethics Committee (IAEC/KMC/113/2019), and experiments were conducted in accordance with the ethical standards approved by the Ministry of Social Justice and Empowerment (Government of India) and the guidelines of Committee for the Purpose of Control and Supervision on Experiments on Animals (CPCSEA)
A significant increase was observed for creatine kinase-MB (CK-MB) (p < 0.001), creatine kinase (CK) (p < 0.001), lactate dehydrogenase (LDH) (p < 0.001), and AST (p < 0.001) in the DOX control group in comparison with normal control
Summary
Cancer survival rates are significantly improving mainly due to the reflection over the past several decades of improved screening, diagnostic imaging, and improvement of therapeutic modalities in oncology. This improved cancer survival rate is associated with treatment-related toxicities that may significantly affect the patient’s health and quality of life [1]. Cardiotoxicity is the prime cause of morbidity and mortality due to DOX treatment among cancer survivors. DOX-induced cardiotoxicity limits its therapeutic application to some extent [8]. E incidence of DOX-induced cardiotoxicity is highly variable amongst studies due to the different definitions of cardiotoxicity and the wide variety of pathology caused by DOX [1, 10,11,12] Dose-dependent cardiotoxicity caused by DOX may occur early at the onset of treatment and even up to many years after completion of treatment [9]. e incidence of DOX-induced cardiotoxicity is highly variable amongst studies due to the different definitions of cardiotoxicity and the wide variety of pathology caused by DOX [1, 10,11,12]
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