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没食子酸甲酯通过抑制氧化应激减轻阿霉素诱导的大鼠心脏毒性。

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

作者信息

Ahmed Akheruz Zaman, Satyam Shakta Mani, Shetty Prakashchandra, D'Souza Melanie Rose

机构信息

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.

出版信息

Scientifica (Cairo). 2021 Jan 13;2021:6694340. doi: 10.1155/2021/6694340. eCollection 2021.

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 ( = 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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e844/7822703/4a279cc275d2/SCIENTIFICA2021-6694340.001.jpg

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