Cardioprotection and myocardial salvage by a disodium disuccinate astaxanthin derivative (Cardax™)
Cardioprotection and myocardial salvage by a disodium disuccinate astaxanthin derivative (Cardax™)
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DOI：
10.1016/j.lfs.2003.12.006
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发表时间：
2004-05-28
期刊：
影响因子：
6.1
通讯作者：
Lockwood, SF
中科院分区：
文献类型：
--
作者：
Gross, GJ;Lockwood, SF
从观察和流行病学研究中已经推断出类胡萝卜素对人类的心脏保护作用，然而，缺乏类胡萝卜素对心脏保护和心肌挽救的直接研究。在本研究中，静脉内（I. V.）在Sprague-Dawley大鼠梗塞模型中评价用新的类胡萝卜素衍生物（二琥珀酸酯虾青素二钠; CardaxTM）预处理作为心肌挽救剂。在第5天进行梗死研究之前，以3种剂量（25、50和75 mg/kg）之一每天一次通过尾静脉注射对动物给药，持续4天。将结果与用盐水溶剂处理的对照动物进行比较。在处死前，左前降支（LAD）冠状动脉闭塞30分钟，然后再灌注2小时，该方案导致平均梗死面积（IS）占风险面积（AAR）的百分比（%）为59 +/-3%。通过专利蓝染料注射定量危险区域，并通过氯化三苯基四唑（TTC）染色测定梗死面积（IS）。Cardax（TM）50和75 mg/kg给药4天，IS/AAR平均值分别显著降低至35 +/- 3%（41%挽救）和26 +/- 2%（56%挽救）。心肌梗死面积和心肌挽救率与再灌注结束时血浆非酯化游离虾青素水平呈显著线性相关。这些结果表明，非肠道Cardax（TM）可能会发现在这些临床应用中的效用，在心肌梗死的风险进行预治疗的患者。(C)2004年爱思唯尔公司All rights reserved.
Cardioprotection in humans by carotenoids has been inferred from observational and epidemiologic studies, however, direct studies of cardioprotection and myocardial salvage by carotenoids are lacking. In the current study, intravenous (I.V.) pre-treatment with a novel carotenoid derivative (disodium disuccinate astaxanthin; Cardax(TM)) was evaluated as a myocardial salvage agent in a Sprague-Dawley rat infarct model. Animals were dosed once per day I.V. by tail vein injection for 4 days at one of 3 doses (25, 50, and 75 mg/kg) prior to the infarct study carried out on day 5. The results were compared with control animals treated with saline vehicle. Thirty (30) minutes of occlusion of the left anterior descending (LAD) coronary artery was followed by 2 hours of reperfusion prior to sacrifice, a regimen which resulted in a mean infarct size (IS) as a percent (%) of the area at risk (AAR) of 59 +/- 3%. Area at risk was quantified by Patent blue dye injection, and infarct size (IS) was determined by triphenyltetrazolium chloride (TTC) staining. Cardax(TM) at 50 and 75 mg/kg for 4 days resulted in a significant mean reduction in IS/AAR to 35 +/- 3% (41% salvage) and 26 +/- 2% (56% salvage), respectively. Infarct size and myocardial salvage were significantly, and linearly, correlated with plasma levels of non-esterified, free astaxanthin at the end of reperfusion. These results suggest that parenteral Cardax(TM) may find utility in those clinical applications where pre-treatment of patients at risk for myocardial infarction is performed. (C) 2004 Elsevier Inc. All rights reserved.