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迷迭香酸对阿霉素诱导的心脏毒性的体内和体外保护作用

In Vivo and In Vitro Protective Effects of Rosmarinic Acid against Doxorubicin-Induced Cardiotoxicity.

作者信息

Rahbardar Mahboobeh Ghasemzadeh, Eisvand Farhad, Rameshrad Maryam, Razavi Bibi Marjan, Hosseinzadeh Hossein

机构信息

Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Nutr Cancer. 2022;74(2):747-760. doi: 10.1080/01635581.2021.1931362. Epub 2021 Jun 4.

Abstract

Doxorubicin (DOX) is an anticancer medicine that may trigger cardiomyopathy. Rosmarinic acid (RA) has shown antioxidant, anti-inflammatory, and anticancer effects. This investigation assessed the cardioprotective effect of RA on DOX-induced-toxicity in both in vivo and in vitro experiments. Male rats were randomized on 7 groups: (1) control, (2) DOX (2 mg/kg, per 48 h, 12d, i.p), (3) RA (40 mg/kg, 12d, i.p.), (4-6) RA (10, 20, 40 mg/kg, 16d, i.p.)+ DOX, (7) Vitamin E (200 mg/kg, per 48 h, 16d, i.p.) + DOX and then indices of cardiac function were estimated. Also, DOX and rosmarinic acid effects were examined on MCF7 cells (breast cancer cells line) to clarify that both cardiotoxicity and anticancer effects were analyzed. DOX increased heart to body weight ratio, RRI, QA, STI, QRS duration and voltage, attenuated HR, blood pressure, Max dP/dt, Min dP/dt, LVDP, enhanced MDA, declined GSH amount, and caused fibrosis and necrosis in cardiac tissue. Administration of RA ameliorated the toxic effects of DOX. In vitro studies showed that RA did not affect the cytotoxic effect of DOX. RA as an antioxidant, anti-inflammatory, and cardioprotective compound could be a promising compound to help minimize DOX-induced cardiotoxicity.

摘要

阿霉素(DOX)是一种可能引发心肌病的抗癌药物。迷迭香酸(RA)已显示出抗氧化、抗炎和抗癌作用。本研究在体内和体外实验中评估了RA对DOX诱导毒性的心脏保护作用。将雄性大鼠随机分为7组:(1)对照组,(2)DOX组(2毫克/千克,每48小时一次,共12天,腹腔注射),(3)RA组(40毫克/千克,共12天,腹腔注射),(4 - 6)RA组(10、20、40毫克/千克,共16天,腹腔注射)+ DOX组,(7)维生素E组(200毫克/千克,每48小时一次,共16天,腹腔注射)+ DOX组,然后评估心脏功能指标。此外,还检测了DOX和迷迭香酸对MCF7细胞(乳腺癌细胞系)的作用,以明确对心脏毒性和抗癌作用均进行了分析。DOX增加了心脏与体重比、RRI、QA、STI、QRS波时限和电压,降低了心率、血压、最大dP/dt、最小dP/dt、左心室舒张压,增加了丙二醛含量,降低了谷胱甘肽含量,并导致心脏组织纤维化和坏死。给予RA可改善DOX的毒性作用。体外研究表明,RA不影响DOX的细胞毒性作用。RA作为一种抗氧化、抗炎和心脏保护化合物,可能是一种有前途的化合物,有助于将DOX诱导的心脏毒性降至最低。

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