Crocin protects against doxorubicin-induced myocardial toxicity in rats through down-regulation of inflammatory and apoptic pathways
Crocin protects against doxorubicin-induced myocardial toxicity in rats through down-regulation of inflammatory and apoptic pathways
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DOI：
10.1016/j.cbi.2016.01.014
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发表时间：
2016-03-05
影响因子：
5.1
通讯作者：
Al-Gayyar, Mohammed M. H.
中科院分区：
文献类型：
--
作者：
Elsherbiny, Nehal M.;Salama, Mohamed F.;Al-Gayyar, Mohammed M. H.
目的：探讨化疗药物的临床应用；阿霉素（DOX）由于其对几个身体器官的毒性作用而受到限制。目前的研究是为了评估藏红花中主要的生物活性成分藏红花素对dox诱导的心肌毒性的心脏保护作用。方法：成年雄性Sprague Dawley大鼠给予DOX （3.5 mg/kg，每周2次）治疗3周，同时给予或不给予每日藏红花素（10和20 mg/kg，口服）治疗3周。结果：DOX注射液显著升高血清天冬氨酸转氨酶（AST）、心肌特异性肌酸激酶（CK-MB）、心肌肌钙蛋白T和乳酸脱氢酶（LDH）水平，并伴有心电图（ECG）损伤，提示DOX诱导心肌毒性。此外，心脏标本检查显示心肌炎症浸润伴多灶性心肌变性/坏死。DOX显著增加抗cd68阳性染色细胞的数量，并显著诱导心肌凋亡。最后，心肌tnf - α、IL-1 β和caspase-3表达显著升高，IL-10显著降低。藏红花素对dox诱导的心肌毒性有明显的剂量依赖性衰减。它改善了心电图谱，恢复了正常的心脏结构。此外，藏红花素还能降低氧化应激，增强宿主抗氧化防御能力，减少细胞凋亡。此外，藏红花素恢复了促炎性和抗炎性细胞因子之间的平衡。在组织病理标本中，生化指标的改善伴随着心肌的显著改善。结论：藏红花素对dox诱导的心肌病有保护作用。藏红花素的抗炎、抗氧化和抗凋亡特性被认为参与了观察到的心脏保护作用。2016爱思唯尔爱尔兰有限公司版权所有。
Aim: The clinical application of the chemotherapeutic agent; Doxorubicin (DOX) is limited by its toxic effects on several body organs. The current study was conducted to evaluate the cardiao-protective effects of crocin, a predominant bioactive constituent of Saffron against DOX-induced myocardial toxicity.Methods: Adult male Sprague Dawley rats received DOX (3.5 mg/kg twice weekly) for 3 weeks with and without daily crocin (10 and 20 mg/kg, orally) for 3 weeks.Results: DOX injection significantly elevated serum levels of aspartate aminotransferase (AST), cardiac specific-creatine kinase (CK-MB), cardiac Troponin T and lactate dehydrogenase (LDH) with impaired electrocardiogram (ECG) profile, indicating DOX-induced myocardial toxicity. Moreover, cardiac specimen examination revealed myocardial inflammatory infiltration with multifocal areas of myocardial degeneration/necrosis. DOX injection significantly increased numbers of active anti-Cd 68 positivity stained cells and significantly-induced myocardial apoptosis. Finally, there was a significant increase in cardiac TNF-alpha, IL-1 beta and caspase-3 expression associated with significant decrease in IL-10. Crocin treatment resulted in a significant dose dependent attenuation of DOX-induced myocardial toxicity. It improved ECG profile and restored normal cardiac architecture. Furthermore, crocin reduced oxidative stress, enhanced host anti-oxidant defenses and decreased apoptosis as well. Additionally, crocin restored the balance between pro-and anti-inflammatory cytokines. The improvement in biochemical parameters was accompanied by significant myocardial improvement as seen in histopathological specimen.Conclusion: Crocin has a cardioprotective effect against DOX-induced cardiomayopathy. Antiinflammatory, antioxidant and antiapoptic properties of crocin are thought to be involved in the observed cardioprotective effect. (C) 2016 Elsevier Ireland Ltd. All rights reserved.