title: Seven day oral supplementation with Cardax (disodium disuccinate astaxanthin) provides significant cardioprotection and reduces oxidative stress in rats.
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.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, 53226, USA.
authors.forename: Garrett J
authors.initials: GJ
authors.lastname: Gross
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hazen
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Lockwood
mesh_terms: D000284:Administration, Oral; D000821:Animal Feed; D000818:Animals; D001682:Biological Availability; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D003331:Coronary Vessels / Q000187:drug effects; D019587:Dietary Supplements; D015227:Lipid Peroxidation / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D015425:Myocardial Reperfusion; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013386:Succinates / Q000627:therapeutic use*; D024341:Xanthophylls; D019207:beta Carotene / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D002316:Cardiotonic Agents; D013386:Succinates; D024341:Xanthophylls; C476770:succinic acid mono-(4-(18-(4-(3-carboxypropionyloxy)-2,6,6-trimethyl-3-oxocyclohex-1-enyl)-3,7,12,16-tetramethyloctadeca-1,3,5,7,9,11,13,15,17-nonaenyl)-3,5,5-trimethyl-2-oxocyclohex-3-enyl) ester; D019207:beta Carotene; C005948:astaxanthine