Folic acid ameliorates celecoxib cardiotoxicity in a doxorubicin heart failure rat model
Folic acid ameliorates celecoxib cardiotoxicity in a doxorubicin heart failure rat model
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DOI：
10.1080/13880209.2017.1299768
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发表时间：
2017-01-01
影响因子：
3.8
通讯作者：
Dubey, Kiran
中科院分区：
文献类型：
--
作者：
Ahmad, Shafique;Panda, Bibhu Prasad;Dubey, Kiran
背景：选择性环加氧酶 2 抑制剂的心脏毒性作用是众所周知的。虽然罗非考昔和伐地考昔已被撤回，但塞来昔布仍在市场上。叶酸是一种天然存在的维生素，已被证明可以减轻大鼠心肌缺血和再灌注后损伤。目的：本研究检测塞来昔布和叶酸对阿霉素诱导的大鼠心肌病的心脏作用。材料和方法：雄性 Wistar 大鼠腹腔注射 6 次 2.5 剂量诱导心肌病。 mg/kg 阿霉素，持续两周。根据血清乳酸脱氢酶（LDH）、肌酸激酶（CK-MB）、肌钙蛋白-T（Tn-T）、肿瘤坏死因子α（TNF-α）、 心脏硫代巴比妥酸反应物 (TBARS) 和谷胱甘肽 (GSH) 水平以及收缩压 (SBP)、心率 (HR) 和超微结构研究。 结果：塞来昔布心脏毒性表现为 LDH、Tn-T、TNF-α、CK-MB、SBP、HR 显着增加 (p< 0.001) 和 单独使用或与阿霉素一起使用时，TBARS (p < 0.01) 水平和 GSH (p < 0.05) 水平显着降低。然而，叶酸与塞来昔布的组合引起了这些参数的显着逆转，并减少了塞来昔布因阿霉素而加剧的心脏毒性。超微结构研究还揭示了这种组合对心肌的保护作用。讨论和结论：叶酸可以防止塞来考昔的心脏毒性作用，这种作用在阿霉素存在时会加剧。对于服用塞来昔布的患者来说，叶酸可能是一种有用的辅助药物。
Context: The cardiotoxic effect of selective cyclo-oxygenase-2 inhibitors is well known. While rofecoxib and valdecoxib have been withdrawn, celecoxib remains on the market. Folic acid, a naturally occurring vitamin, has been shown to reduce myocardial ischemia and post-reperfusion injury in rats.Objective: This study examined the cardiac effects of celecoxib and folic acid on doxorubicin-induced cardiomyopathy in rats.Materials and methods: Cardiomyopathy was induced in male Wistar rats with six intraperitoneal injections of 2.5 mg/kg doxorubicin over a period of two weeks. The effect of 28 days of celecoxib (100 mg/kg/day) and its combination with folic acid (10mg/kg/day) was studied on doxorubicin-induced cardiomyopathy according to serum lactate dehydrogenase (LDH), creatine kinase (CK-MB), troponin-T (Tn-T), tumor necrosis factor alpha (TNF-alpha), cardiac thiobarbituric acid reactive substance (TBARS), and glutathione (GSH) levels as well as systolic blood pressure (SBP), heart rate (HR) and ultrastructural studies.Results: Celecoxib cardiotoxicity was manifested by significant increases in the LDH, Tn-T, TNF-alpha, CK-MB, SBP, HR (p< 0.001) and TBARS (p< 0.01) levels and a significant decrease in the GSH (p< 0.05) level when used alone or administered with doxorubicin. However, the combination of folic acid with celecoxib caused a significant reversal of these parameters and reduced the cardiotoxicity of celecoxib that was aggravated by doxorubicin. The ultrastructural study also revealed myocardial protection with this combination.Discussion and conclusion: Folic acid protects against the cardiotoxic effects of celecoxib, which are aggravated in the presence of doxorubicin. Folic acid may act as a useful adjunct in patients who are taking celecoxib.