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Montelukast ameliorates doxorubicin-induced cardiotoxicity via modulation of p-glycoprotein and inhibition of ROS-mediated TNF-α/NF-κB pathways
Drug and Chemical Toxicology ( IF 2.6 ) Pub Date : 2020-02-27 , DOI: 10.1080/01480545.2020.1730885
Heba M Hafez 1 , Hanaa Hassanein 2
Affiliation  

Abstract

Doxorubicin (DOX) cardiotoxicity remains an obstacle to clinical use. The current study examined the possible role of montelukast (ML), which is a cysteinyl leukotrienes receptor antagonist against DOX-induced cardiotoxicity. Male Wistar rats were divided into five groups. The control group, ML group, DOX-challenged group, and DOX/ML-treated groups received ML10 and 20 mg/kg/day for 14 days. Cardiac enzymes; lactate dehydrogenase (LDH); and creatine kinase MB (CK-MB) isoenzymes in serum were measured. Cardiac oxidative/antioxidative parameters were also measured. Cardiac samples were examined for histological images and immunohistochemical expression of tumor necrosis factor alpha (TNF-α)/survivin. Quantitative real-time-polymerase chain reaction was used to detect levels of interleukin (IL)-1β/caspase-3 mRNA. The levels of P-glycoprotein (P-gp), nuclear factor-kappa B , and reactive oxygen species were estimated by enzyme-linked immunosorbent assay. DOX increased serum cardiac enzymes along with oxidative, inflammatory, and apoptotic markers. Both doses of ML significantly ameliorated cardiac enzymes and attenuated all oxidative stress parameters with the enhancement of P-gp activity. It was concluded that ML may be a valuable cardioprotective adjuvant during DOX use.



中文翻译:

孟鲁司特通过调节 p-糖蛋白和抑制 ROS 介导的 TNF-α/NF-κB 通路改善阿霉素诱导的心脏毒性

摘要

多柔比星 (DOX) 心脏毒性仍然是临床使用的障碍。目前的研究检查了孟鲁司特 (ML) 的可能作用,它是一种半胱氨酰白三烯受体拮抗剂,可对抗 DOX 诱导的心脏毒性。雄性Wistar大鼠分为五组。对照组、ML 组、DOX 攻击组和 DOX/ML 治疗组接受 ML10 和 20 mg/kg/天,持续 14 天。心脏酶; 乳酸脱氢酶 (LDH); 测量了血清中的肌酸激酶 MB (CK-MB) 同工酶。还测量了心脏氧化/抗氧化参数。检查心脏样本的组织学图像和肿瘤坏死因子α(TNF-α)/存活素的免疫组织化学表达。定量实时聚合酶链反应用于检测白细胞介素 (IL)-1β/caspase-3 mRNA 的水平。P-糖蛋白(P-gp)的水平,核因子-kappa B 和活性氧物质通过酶联免疫吸附测定进行估计。DOX 增加血清心肌酶以及氧化、炎症和凋亡标志物。两种剂量的 ML 都显着改善了心肌酶,并随着 P-gp 活性的增强而减弱了所有氧化应激参数。得出的结论是,ML 在 DOX 使用期间可能是一种有价值的心脏保护佐剂。

更新日期:2020-02-27
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