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辅酶 Q10 和赖诺普利对阿霉素诱导的大鼠心脏毒性的保护作用:体视学和心电图研究。

The Protective Effects of Coenzyme Q10 and Lisinopril Against Doxorubicin-Induced Cardiotoxicity in Rats: A Stereological and Electrocardiogram Study.

机构信息

Department of Biology, Islamic Azad University, Shiraz Branch, Shiraz, Iran.

Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Zand Ave., 71348-45794, Shiraz, Iran.

出版信息

Cardiovasc Toxicol. 2021 Nov;21(11):936-946. doi: 10.1007/s12012-021-09685-8. Epub 2021 Aug 2.

Abstract

Doxorubicin (DOX) is used as an anticancer drug despite its several side effects, especially its irreversible impacts on cardiotoxicity. Coenzyme Q10 (Q10) as a powerful antioxidant and lisinopril (LIS) as an angiotensin-converting enzyme inhibitor seem to provide protection against DOX-induced cardiotoxicity. Therefore, this study aimed to assess the cardioprotective effects of Q10 and LIS against DOX-induced cardiotoxicity in rats. Adult male Sprague-Dawley rats were randomly assigned into the control, LIS, Q10, DOX, DOX + LIS, and DOX + Q10 groups. On day 21, ECG was recorded and the right ventricle was dissected for evaluation of catalase activity and malondialdehyde (MDA) concentration. Additionally, the left ventricle and the sinoatrial (SA) node were dissected to assess the stereological parameters. The results of ECG indicated bradycardia and increase in QRS duration and QT interval in the DOX group compared to the control group. Meanwhile, the total volumes of the left ventricle, myocytes, and microvessels and the number of cardiomyocyte nuclei decreased, whereas the total volume of the connective tissue and the mean volume of cardiomyocytes increased in the DOX group. On the other hand, the SA node and the connective tissue were enlarged, while the volume of the SA node nuclei was reduced in the DOX group. Besides, catalase activity was lower and MDA concentration was higher in the DOX-treated group. Q10 could recover most stereological parameters, catalase activity, and MDA concentration. LIS also prevented some stereological parameters and ECG changes and improved catalase activity and MDA concentration in the DOX group. The findings suggested that Q10 and LIS exerted cardioprotective effects against DOX-induced cardiac toxicity.

摘要

多柔比星(DOX)是一种抗癌药物,尽管它有许多副作用,特别是对心脏毒性的不可逆影响。辅酶 Q10(Q10)作为一种强大的抗氧化剂和赖诺普利(LIS)作为血管紧张素转换酶抑制剂,似乎对 DOX 诱导的心脏毒性具有保护作用。因此,本研究旨在评估 Q10 和 LIS 对 DOX 诱导的大鼠心脏毒性的心脏保护作用。成年雄性 Sprague-Dawley 大鼠被随机分为对照组、LIS 组、Q10 组、DOX 组、DOX+LIS 组和 DOX+Q10 组。第 21 天,记录心电图,并解剖右心室以评估过氧化氢酶活性和丙二醛(MDA)浓度。此外,解剖左心室和窦房结(SA)以评估体视学参数。心电图结果表明,与对照组相比,DOX 组出现心动过缓以及 QRS 持续时间和 QT 间期增加。同时,左心室、心肌细胞和微血管的总容积以及心肌细胞核的数量减少,而 DOX 组的结缔组织总容积和心肌细胞的平均容积增加。另一方面,SA 节点和结缔组织增大,而 DOX 组的 SA 节点核体积减小。此外,DOX 处理组过氧化氢酶活性降低,MDA 浓度升高。Q10 可以恢复大多数体视学参数、过氧化氢酶活性和 MDA 浓度。LIS 还可以预防一些体视学参数和心电图变化,并改善 DOX 组的过氧化氢酶活性和 MDA 浓度。研究结果表明,Q10 和 LIS 对 DOX 诱导的心脏毒性具有心脏保护作用。

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