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Disodium Disuccinate Astaxanthin (Cardax) Attenuates Complement Activation and Reduces Myocardial Injury following Ischemia/Reperfusion
Carotenoids are a naturally occurring group of compounds that possess antioxidant properties. Most natural carotenoids display poor aqueous solubility and tend to form aggregates in solution. Disodium disuccinate astaxanthin (DDA; Cardax) is a water-dispersible synthetic carotenoid that rapidly and...
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Published in: | The Journal of pharmacology and experimental therapeutics 2005-08, Vol.314 (2), p.686-692 |
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Main Authors: | , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Carotenoids are a naturally occurring group of compounds that possess antioxidant properties. Most natural carotenoids display
poor aqueous solubility and tend to form aggregates in solution. Disodium disuccinate astaxanthin (DDA; Cardax) is a water-dispersible
synthetic carotenoid that rapidly and preferentially associates with serum albumin, thereby preventing the formation of supramolecular
complexes and facilitating its efficacy after parenteral administration. This study investigated the ability of DDA to reduce
inflammation and myocardial injury in a rabbit model of ischemia/reperfusion. DDA (50 mg/kg/day) or saline was administered
i.v. for 4 consecutive days before the initiation of the protocol for induction of myocardial ischemia/reperfusion. On the
5th day, rabbits underwent 30 min of coronary artery occlusion, followed by a 3-h reperfusion period. Myocardial infarct size,
as a percentage of the area at risk, was calculated for both groups. Infarct size was 52.5 ± 7.5% in the vehicle-treated ( n = 9) and 25.8 ± 4.7% in the DDA-treated ( n = 9) animals ( p < 0.01 versus vehicle; mean myocardial salvage = 51%). To evaluate the anti-inflammatory effects of DDA, complement activity
was assessed at the end of reperfusion using a red blood cell lysis assay. DDA administration significantly reduced ( p < 0.01) the activation of the complement system in the serum. The current results, coupled with the well established antioxidant
ability of carotenoids, suggest that the mechanism(s) of action by which DDA reduces the tissue damage associated with reperfusion
injury may include both antioxidant and anticomplement components. |
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ISSN: | 0022-3565 1521-0103 |
DOI: | 10.1124/jpet.105.087114 |