Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
J Biochem Mol Toxicol. 2020 Jul;34(7):e22492. doi: 10.1002/jbt.22492. Epub 2020 Mar 15.
The use of the cytotoxic antibiotic doxorubicin (DOXR) is limited by its dose-dependent cardiotoxicity. The aim of this study was to evaluate the cardioprotective effect of the combination of carvedilol (CARD) and liposomal resveratrol (LIPO RESV) against DOXR-induced cardiomyopathy in rats. The results of the present study showed that DOXR administration significantly increased heart weight/body weight ratio by 35.6%, creatine kinase-MB (CK-MB) by 40.6%, troponin-I levels by 85%, and decreased reduced glutathione level and superoxide dismutase activity by 47% and 52%, respectively compared to the control group. Moreover, cardiac caspase-3 protein expression was upregulated by 51.6% vs the control group. In contrast, treatment of DOXR-administered rats with CARD, RESV, or LIPO RESV and their combination for 6 weeks improved all the above-mentioned measured parameters. In conclusion, concomitant administration of CARD and LIPO RESV exerted additive pharmacological effects in some measured parameters against DOXR-induced cardiomyopathy and this may be a useful cardioprotective strategy.
阿霉素(DOXR)的细胞毒性抗生素的使用受到其剂量依赖性心脏毒性的限制。本研究旨在评估卡维地洛(CARD)和脂质体白藜芦醇(LIPO RESV)联合使用对 DOXR 诱导的大鼠心肌病的心脏保护作用。本研究结果表明,与对照组相比,DOXR 给药使心脏重量/体重比增加了 35.6%,肌酸激酶-MB(CK-MB)增加了 40.6%,肌钙蛋白-I 水平增加了 85%,还原型谷胱甘肽水平和超氧化物歧化酶活性分别降低了 47%和 52%。此外,心脏半胱天冬酶-3 蛋白表达上调了 51.6%。相比之下,6 周时用 CARD、RESV、LIPO RESV 或它们的组合治疗 DOXR 给药大鼠改善了上述所有测量参数。总之,CARD 和 LIPO RESV 的同时给药对 DOXR 诱导的心肌病在一些测量参数上表现出相加的药理作用,这可能是一种有用的心脏保护策略。