Ahmed Akheruz Zaman, Satyam Shakta Mani, Shetty Prakashchandra, D'Souza Melanie Rose
Department of Anatomy, Melaka Manipal Medical College (Manipal Campus), Manipal Academy of Higher Education, Manipal-576104, Karnataka, India.
Department of Pharmacology, Melaka Manipal Medical College (Manipal Campus), Manipal Academy of Higher Education, Manipal-576104, Karnataka, India.
Scientifica (Cairo). 2021 Jan 13;2021:6694340. doi: 10.1155/2021/6694340. eCollection 2021.
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 ( = 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 8 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 ( < 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 ( < 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.
阿霉素诱导的心脏毒性是癌症幸存者发病和死亡的主要原因。本研究旨在探讨棓酸甲酯(一种活性多酚类营养保健品)对阿霉素诱导的Wistar大鼠心脏毒性的心脏保护潜力。将24只雌性Wistar大鼠(150 - 200克)分为四组(每组 = 6只),分别为正常对照组(I组)、阿霉素对照组(II组)、试验A组(III组)和试验B组(IV组)。III组和IV组动物分别口服150毫克/千克/天和300毫克/千克/天的棓酸甲酯进行预防性治疗,持续7天。在第7天,通过腹腔注射途径给II组、III组和IV组动物注射阿霉素(25毫克/千克;单次剂量)以诱导急性心脏毒性。在第8天,除了进行心电图分析外,还检测了血清肌酸激酶(CK)、肌酸激酶同工酶(CK - MB)、乳酸脱氢酶(LDH)、天冬氨酸转氨酶(AST)、丙二醛(MDA)和谷胱甘肽(GSH)。在对离体心脏进行大体检查后,通过光学显微镜进行组织病理学评估。与正常对照组大鼠相比,在阿霉素对照组大鼠中观察到了显著(P < 0.05)的心脏损伤以及氧化应激。两种剂量的棓酸甲酯均显著(P < 0.05)降低了阿霉素诱导的心电图变化、血脂异常以及CK、CK - MB、LDH、AST、MDA的升高,并提高了GSH水平。棓酸甲酯逆转了阿霉素诱导的心脏组织病理学变化。本研究表明,棓酸甲酯通过抑制氧化应激对阿霉素诱导的雌性Wistar大鼠心脏毒性发挥心脏保护作用。我们的研究为临床研究开辟了前景,考虑将棓酸甲酯作为一种潜在的化学保护营养保健品,用于与阿霉素联合化疗以限制其心脏毒性。