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连续七天口服Cardax(二琥珀酸虾青素二钠)可对大鼠起到显著的心脏保护作用,并减轻其氧化应激反应。

Seven day oral supplementation with Cardax (disodium disuccinate astaxanthin) provides significant cardioprotection and reduces oxidative stress in rats.

作者信息

Gross Garrett J, Hazen Stanley L, Lockwood Samuel F

机构信息

Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, 53226, USA.

出版信息

Mol Cell Biochem. 2006 Feb;283(1-2):23-30. doi: 10.1007/s11010-006-2217-6.

Abstract

In the current study, the improved oral bioavailability of a synthetic astaxanthin derivative (Cardax; disodium disuccinate astaxanthin) was utilized to evaluate its potential effects as a cardioprotective agent after 7-day subchronic oral administration as a feed supplement to Sprague-Dawley rats. Animals received one of two concentrations of Cardax in feed (0.1 and 0.4%; approximately 125 and 500 mg/kg/day, respectively) or control feed without drug for 7 days prior to the infarct study carried out on day 8. Thirty minutes of occlusion of the left anterior descending (LAD) coronary artery was followed by 2 h of reperfusion prior to sacrifice, a regimen which resulted in a mean infarct size (IS) as a percentage (%) of the area at risk (AAR; IS/AAR,%) of 61 +/- 1.8%. The AAR was quantified by Patent blue dye injection, and IS was determined by triphenyltetrazolium chloride (TTC) staining. Cardax at 0.1 and 0.4% in feed for 7 days resulted in a significant mean reduction in IS/AAR,% to 45 +/- 2.0% (26% salvage) and 39 +/- 1.5% (36% salvage), respectively. Myocardial levels of free astaxanthin achieved after 7-day supplementation at each of the two concentrations (400 +/- 65 nM and 1634 +/- 90 nM, respectively) demonstrated excellent solid-tissue target organ loading after oral supplementation. Parallel trends in reduction of plasma levels of multiple lipid peroxidation products with disodium disuccinate astaxanthin supplementation were observed, consistent with the documented in vitro antioxidant mechanism of action. These results extend the potential utility of this compound for cardioprotection to the elective human cardiovascular patient population, for which 7-day oral pre-treatment (as with statins) provides significant reductions in induced periprocedural infarct size.

摘要

在本研究中,利用合成虾青素衍生物(Cardax;虾青素二琥珀酸钠)口服生物利用度的提高,在对Sprague-Dawley大鼠进行为期7天的亚慢性口服给药作为饲料补充剂后,评估其作为心脏保护剂的潜在作用。在第8天进行梗死研究前7天,动物接受饲料中两种浓度之一的Cardax(0.1%和0.4%;分别约为125和500mg/kg/天)或不含药物的对照饲料。在处死前,左前降支(LAD)冠状动脉闭塞30分钟,随后再灌注2小时,该方案导致平均梗死面积(IS)占危险面积(AAR;IS/AAR,%)的百分比为61±1.8%。通过专利蓝染料注射对AAR进行定量,通过氯化三苯基四氮唑(TTC)染色确定IS。饲料中0.1%和0.4%的Cardax喂养7天,导致IS/AAR,%显著平均降低至45±2.0%(挽救26%)和39±1.5%(挽救36%)。在两种浓度下进行7天补充后,心肌中游离虾青素水平(分别为400±65nM和1634±90nM)显示口服补充后具有优异的实体组织靶器官负载。观察到补充虾青素二琥珀酸钠后多种脂质过氧化产物血浆水平降低的平行趋势,这与已记录的体外抗氧化作用机制一致。这些结果将该化合物对心脏保护的潜在用途扩展到选择性的人类心血管疾病患者群体,对于该群体,7天口服预处理(与他汀类药物一样)可显著降低诱导的围手术期梗死面积。

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