Methyl Gallate Attenuates Doxorubicin-Induced Cardiotoxicity in Rats by Suppressing Oxidative Stress

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.

An in vivo and in vitro model on the protective effect of corilagin on doxorubicin‐induced cardiotoxicity via regulation of apoptosis and PI3‐K/AKT signaling pathways

“…DOX (25 mg/kg bw; single dose) was intraperitoneally administered to group III, and IV animals to induce acute cardiotoxicity. [ 11 ] At the final stage of the experiment, all experimental rats were ethically anesthetized by xylazine/ketamine (24 mg/kg/day). Then, animals were sacrificed by cervical decapitation.…”

Plicosepalus acacia Extract and Its Major Constituents, Methyl Gallate and Quercetin, Potentiate Therapeutic Angiogenesis in Diabetic Hind Limb Ischemia: HPTLC Quantification and LC-MS/MS Metabolic Profiling

“…Methyl gallate was reported to be a potent antioxidant that inhibits oxidative stress in human adipocytes [ 80 ]. The antioxidant capabilities of methyl gallate also helped to attenuate doxorubicin-induced cardiotoxicity in rats [ 81 ].…”

“…adipocytes [80]. The antioxidant capabilities of methyl gallate also helped to attenuate doxorubicin-induced cardiotoxicity in rats [81].…”

Anticancer Drug-Induced Cardiotoxicity: Insights and Pharmacogenetics

“…CHF, restrictive cardiomyopathy, coronary artery disease, valvular heart disease, constrictive pericarditis, and pericardial effusion are all conditions that affect the heart [ 156 ]. However, the chances of cardiac toxicity are found to be higher in patients undergoing radiation therapy along with the contemporary administration of chemotherapeutic agents [ 157 ]. Radiation therapy is used to treat diseases such as lymphoma, breast cancer, thymoma, high and low respiratory tracts, and esophageal and gastric lesions, among others.…”