Seven day oral supplementation with Cardax™ (disodium disuccinate astaxanthin) provides significant cardioprotection and reduces oxidative stress in rats
Seven day oral supplementation with Cardax™ (disodium disuccinate astaxanthin) provides significant cardioprotection and reduces oxidative stress in rats
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DOI：
10.1007/s11010-006-2217-6
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发表时间：
2006-02-01
影响因子：
4.3
通讯作者：
Lockwood, SF
中科院分区：
文献类型：
--
作者：
Gross, GJ;Hazen, SL;Lockwood, SF
在当前的研究中，合成的虾青素衍生物（CardaxTM;二琥珀酸酯虾青素二钠）的改善的口服生物利用度被用于评价其作为饲料补充剂亚慢性口服给药Sprague-Dawley大鼠7天后作为心脏保护剂的潜在作用。在第8天进行梗塞研究之前，动物在饲料中接受两种浓度之一的CardaxTM（0.1%和0.4%;分别类似于125和500 mg/kg/天）或对照饲料而不给药7天。左前降支（LAD）冠状动脉闭塞30分钟后，处死前再灌注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定量AAR，通过氯化三苯基四唑（TTC）染色测定IS。在饲料中以0.1%和0.4%的Cardax（TM）持续7天导致IS/AAR的显著平均降低，分别为45 +/- 2.0%（26%挽救）和39 +/- 1.5%（36%挽救）。在两种浓度（分别为400 +/- 65 nM和1634 +/- 90 nM）的每种浓度下补充7天后获得的游离虾青素的心肌水平证明了口服补充后优异的固体组织靶器官负荷。观察到补充二琥珀酸二钠虾青素的多种脂质过氧化产物的血浆水平降低的平行趋势，与记录的体外抗氧化作用机制一致。这些结果将该化合物用于心脏保护的潜在效用扩展至择期人类心血管患者群体，对于该人群，7天口服预处理（与他汀类药物一样）提供了诱导的围手术期梗死面积的显著减少。
In the current study, the improved oral bioavailability of a synthetic astaxanthin derivative ( Cardax(TM); 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(TM) in feed (0.1 and 0.4%; similar to 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(TM) 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.