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通过槲皮素干预减轻阿霉素诱导的心脏毒性:大鼠实验研究

Mitigating Doxorubicin-Induced Cardiotoxicity through Quercetin Intervention: An Experimental Study in Rats.

作者信息

Dulf Patricia Lorena, Coadă Camelia Alexandra, Florea Adrian, Moldovan Remus, Baldea Ioana, Dulf Daniel Vasile, Blendea Dan, Filip Adriana Gabriela

机构信息

Faculty of Medicine, Iuliu Haţieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.

Department of Molecular Sciences, Iuliu Haţieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.

出版信息

Antioxidants (Basel). 2024 Aug 31;13(9):1068. doi: 10.3390/antiox13091068.

DOI:10.3390/antiox13091068
PMID:39334727
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11429272/
Abstract

Doxorubicin (DOX) is an effective anticancer drug, but its use is limited by dose-dependent heart toxicity. Quercetin is a natural antioxidant frequently studied for its beneficial properties. Moreover, a wide range of dietary supplements are available for human use. This in vivo study aimed to explore the potential cardioprotective effects of quercetin in chronic DOX treatment. A total of 32 Wistar rats were randomly divided into four groups: control, DOX, DOX/Q-50, and DOX/Q-100, treated with saline, 2.5 mg/kg body-weight DOX, 2.5 mg/kg body-weight DOX + 50 mg quercetin, and 2.5 mg/kg body-weight DOX + 100 mg quercetin, respectively, for two weeks. Rats were monitored using cardiac ultrasound (US) and markers for cardiac injury. Oxidative damage and ultrastructural changes in the heart were investigated. Chronic DOX treatment led to a decline in cardiac function and elevated values of NT pro-BNP, troponin I, and CK-MB. Quercetin treatment slightly improved certain US parameters, and normalized serum NT pro-BNP levels. Furthermore, DOX-induced SOD1 depletion with consequent Nrf2 activation and DNA damage as shown by an increase in γH2AX and 8HOdG. Quercetin treatment alleviated these alterations. Oral administration of quercetin alleviated serum markers associated with DOX-induced cardiotoxicity. Furthermore, it exhibited a favorable impact on the cardiac US parameters. This suggests that quercetin may have potential cardioprotective properties.

摘要

阿霉素(DOX)是一种有效的抗癌药物,但其使用受到剂量依赖性心脏毒性的限制。槲皮素是一种因其有益特性而经常被研究的天然抗氧化剂。此外,有多种膳食补充剂可供人类使用。本体内研究旨在探讨槲皮素在慢性DOX治疗中的潜在心脏保护作用。总共32只Wistar大鼠被随机分为四组:对照组、DOX组、DOX/Q - 50组和DOX/Q - 100组,分别用生理盐水、2.5毫克/千克体重的DOX、2.5毫克/千克体重的DOX + 50毫克槲皮素以及2.5毫克/千克体重的DOX + 100毫克槲皮素处理两周。使用心脏超声(US)和心脏损伤标志物对大鼠进行监测。研究了心脏的氧化损伤和超微结构变化。慢性DOX治疗导致心脏功能下降以及NT pro - BNP、肌钙蛋白I和CK - MB值升高。槲皮素治疗略微改善了某些US参数,并使血清NT pro - BNP水平恢复正常。此外,DOX诱导SOD1耗竭,随后Nrf2激活以及DNA损伤,表现为γH2AX和8 - OHdG增加。槲皮素治疗减轻了这些改变。口服槲皮素减轻了与DOX诱导的心脏毒性相关的血清标志物。此外,它对心脏US参数产生了有利影响。这表明槲皮素可能具有潜在的心脏保护特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e970/11429272/63788bb18159/antioxidants-13-01068-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e970/11429272/ad4beb4e3bd1/antioxidants-13-01068-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e970/11429272/9759485f52c3/antioxidants-13-01068-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e970/11429272/3ade20f02501/antioxidants-13-01068-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e970/11429272/8d1679811188/antioxidants-13-01068-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e970/11429272/ce82aadcc4f1/antioxidants-13-01068-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e970/11429272/dc36959723bb/antioxidants-13-01068-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e970/11429272/63788bb18159/antioxidants-13-01068-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e970/11429272/ad4beb4e3bd1/antioxidants-13-01068-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e970/11429272/9759485f52c3/antioxidants-13-01068-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e970/11429272/3ade20f02501/antioxidants-13-01068-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e970/11429272/8d1679811188/antioxidants-13-01068-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e970/11429272/ce82aadcc4f1/antioxidants-13-01068-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e970/11429272/dc36959723bb/antioxidants-13-01068-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e970/11429272/63788bb18159/antioxidants-13-01068-g007.jpg

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