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枸杞对阿霉素诱导的心脏毒性的保护作用。

Protective effect of Lycium barbarum on doxorubicin-induced cardiotoxicity.

作者信息

Xin Yan-Fei, Zhou Guo-Liang, Deng Zu-Yue, Chen Yun-Xiang, Wu Yue-Guo, Xu Pan-Sheng, Xuan Yao-Xian

机构信息

State Key Laboratory of Safety Evaluation for New Drug, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, China.

出版信息

Phytother Res. 2007 Nov;21(11):1020-4. doi: 10.1002/ptr.2186.

Abstract

The objective of this work was to explore the hypothesis that Lycium barbarum (LB) may be protective against doxorubicin (DOX)-induced cardiotoxicity through antioxidant-mediated mechanisms. Male SD rats were treated with distilled water or a water extract of LB (25 mg/kg, p.o.) daily and saline or DOX (5 mg/kg, i.v.) weekly for 3 weeks. Mortality, general condition and body weight were observed during the experiment. DOX-induced cardiotoxicity was assessed by electrocardiograph, heart antioxidant activity, serum levels of creatine kinase (CK) and aspartate aminotransferase (AST) and histopathological change. The DOX group showed higher mortality (38%) and worse physical characterization. Moreover, DOX caused myocardial injury manifested by arrhythmias and conduction abnormalities in ECG (increased QT and ST intervals and ST elevation), a decrease of heart antioxidant activity, an increase of serum CK and AST, as well as myocardial lesions. Pretreatment with LB significantly prevented the loss of myofibrils and improved the heart function of the DOX-treated rats as evidenced from lower mortality (13%), normalization of antioxidative activity and serum AST and CK, as well as improving arrhythmias and conduction abnormalities. These results suggested that LB elicited a typical cardioprotective effect on DOX-related oxidative stress. Furthermore, in vitro cytotoxic study showed the antitumor activity of DOX was not compromised by LB. It is possible that LB could be used as a useful adjunct in combination with DOX chemotherapy.

摘要

本研究的目的是探讨枸杞(LB)可能通过抗氧化介导机制预防阿霉素(DOX)诱导的心脏毒性这一假说。雄性SD大鼠每天接受蒸馏水或枸杞水提取物(25mg/kg,口服)处理,每周接受生理盐水或阿霉素(5mg/kg,静脉注射)处理,持续3周。实验期间观察死亡率、一般状况和体重。通过心电图、心脏抗氧化活性、血清肌酸激酶(CK)和天冬氨酸转氨酶(AST)水平以及组织病理学变化评估阿霉素诱导的心脏毒性。阿霉素组显示出较高的死亡率(38%)和较差的身体特征。此外,阿霉素导致心肌损伤,表现为心电图中的心律失常和传导异常(QT和ST间期延长以及ST段抬高)、心脏抗氧化活性降低、血清CK和AST升高以及心肌病变。枸杞预处理显著预防了肌原纤维的损失,并改善了阿霉素处理大鼠的心脏功能,较低的死亡率(13%)、抗氧化活性以及血清AST和CK的正常化以及心律失常和传导异常的改善证明了这一点。这些结果表明,枸杞对阿霉素相关的氧化应激具有典型的心脏保护作用。此外,体外细胞毒性研究表明,枸杞不会损害阿霉素的抗肿瘤活性。枸杞有可能作为阿霉素化疗有用的辅助药物。

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