title: Disodium Disuccinate Astaxanthin (Cardax) attenuates complement activation and reduces myocardial injury following ischemia/reperfusion.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Michigan Medical School, 1301C MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA.
authors.forename: D Adam
authors.initials: DA
authors.lastname: Lauver
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Lockwood
authors.forename: Benedict R
authors.initials: BR
authors.lastname: Lucchesi
mesh_terms: D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism; D003167:Complement Activation / Q000187:drug effects*; D003169:Complement Inactivator Proteins; D015938:Complement Membrane Attack Complex / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D006439:Hemodynamics / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D011817:Rabbits; D013778:Tetrazolium Salts; D013844:Thiazoles; D014018:Tissue Distribution; D019210:Troponin I / Q000097:blood / Q000378:metabolism; D024341:Xanthophylls; D019207:beta Carotene / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D003169:Complement Inactivator Proteins; D015938:Complement Membrane Attack Complex; D013778:Tetrazolium Salts; D013844:Thiazoles; D019210:Troponin I; D024341:Xanthophylls; D019207:beta Carotene; C005948:astaxanthine; D002097:C-Reactive Protein; C022616:thiazolyl blue