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藏红花素对亚慢性暴露敌敌畏诱导大鼠心脏毒性的保护作用。

Protective effect of crocin on diazinon induced cardiotoxicity in rats in subchronic exposure.

机构信息

Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Chem Biol Interact. 2013 May 25;203(3):547-55. doi: 10.1016/j.cbi.2013.03.010. Epub 2013 Mar 21.

Abstract

UNLABELLED

This study was designed to evaluate the effectiveness of crocin, main component of Crocus sativus L. (Saffron) against subchronic diazinon (DZN) induced cardiotoxicity in rats.

METHODS

Rats were divided into 7 groups; control (corn oil, gavage), DZN (15 mg/kg/day, gavage,), crocin (12.5, 25 or 50 mg/kg/day, i.p) plus DZN, vitamin E (200 IU/kg, i.p, three times per week) plus DZN and crocin (50 mg/kg/day, i.p) groups. Treatments were continued for 4 weeks. Creatine phosphokinase MB (CK-MB), malondealdehyde (MDA) and glutathione (GSH) levels were evaluated in heart tissue at the end of treatments. Levels of apoptotic proteins (Bax, Bcl2, caspase 3) and cytosolic cytochrome c were analyzed by Western blotting. Transcript levels of Bax and Bcl2 were also determined using qRT PCR.

RESULTS

DZN induced histophatological damages and elevated the level of cardiac marker CK-MB. These effects were associated with increased MDA level, lower level of reduced GSH and induction of apoptosis through elevation of Bax/Bcl2 ratio (both protein and mRNA levels), cytochrome c release to the cytosol and activation caspase 3 in cardiac tissue. Crocin (25 and 50 mg/kg) or vitamin E improved histopathological damages, decreased MDA and CK-MB, increased GSH content and attenuated the increase of Bax/Bcl2 ratio, activation of caspase 3 and release of cytochrome c to the cytosol induced by DZN. In summary, DZN induced mitochondrial-mediated apoptosis in heart tissue of rat following subchronic exposure. Crocin, as an antioxidant, showed protective effects against DZN cardiotoxicity by reducing lipid peroxidation and alleviating apoptosis.

摘要

目的

本研究旨在评估藏红花主要成分西红花苷(藏红花)对大鼠亚慢性敌敌畏(DZN)诱导的心脏毒性的有效性。

方法

将大鼠分为 7 组:对照组(玉米油,灌胃)、DZN 组(15mg/kg/天,灌胃)、西红花苷组(12.5、25 或 50mg/kg/天,腹腔注射)加 DZN、维生素 E 组(200IU/kg,腹腔注射,每周 3 次)加 DZN 和西红花苷组(50mg/kg/天,腹腔注射)。治疗持续 4 周。在治疗结束时评估心脏组织中肌酸磷酸激酶 MB(CK-MB)、丙二醛(MDA)和谷胱甘肽(GSH)的水平。通过 Western 印迹分析凋亡蛋白(Bax、Bcl2、caspase 3)和胞质细胞色素 c 的水平。还使用 qRT-PCR 测定 Bax 和 Bcl2 的转录水平。

结果

DZN 诱导组织病理学损伤并升高心脏标志物 CK-MB 的水平。这些影响与 MDA 水平升高、还原 GSH 水平降低以及通过增加 Bax/Bcl2 比值(蛋白和 mRNA 水平)、细胞色素 c 向细胞质释放和激活 caspase 3 诱导凋亡有关。西红花苷(25 和 50mg/kg)或维生素 E 可改善组织病理学损伤,降低 MDA 和 CK-MB,增加 GSH 含量,并减弱 DZN 诱导的 Bax/Bcl2 比值增加、caspase 3 激活和细胞色素 c 向细胞质释放。总之,DZN 在大鼠亚慢性暴露后诱导心脏组织中线粒体介导的细胞凋亡。西红花苷作为一种抗氧化剂,通过减少脂质过氧化和缓解凋亡来显示对 DZN 心脏毒性的保护作用。

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