Disodium disuccinate astaxanthin has potent cardioprotective effects in animals, with demonstrated preclinical efficacy in the rat, rabbit, and canine models of experimental
infarction. It has been effective in subchronic and acute dosing regimens after parenteral administration, and recently published data in rats demonstrate that oral cardioprotection is also readily achieved. Myocardial salvage in the canine can reach 100% with a 4-day subchronic dosing regimen; single-dose I.V. cardioprotection, when given 2 hours before experimental
coronary occlusion, is on average two-thirds of that achieved with the subchronic regimen in dogs. In conscious animals, no effects on hemodynamic parameters have been observed. Recently, the beneficial properties of this prototypical
astaxanthin conjugate have been extended to include second- and third-generation compounds with improved pharmacokinetic and/or potency profiles. The primary mechanism of cardioprotection appears to be
antioxidant activity: potent direct scavenging of the lynchpin radical in
ischemia-reperfusion injury,
superoxide anion, has been documented in appropriate model systems. In addition, modulation of serum
complement activity, reduction of the levels of deposition of
C-reactive protein (CRP) and the
membrane attack complex (MAC) in infarcted tissue, and reduction in oxidative stress markers from the
arachidonic acid and
linoleic acid pathways also suggest a significant anti-inflammatory component to the mechanism of cardioprotection. Favorable
plasma protein binding has been demonstrated in vitro for several
astaxanthin conjugates; this binding capacity overcomes the supramolecular assembly of the compounds that occurs in aqueous
solution, which in itself improves the stability and shelf-life of aqueous formulations.
Astaxanthin readily populates cardiac tissue after metabolic hydrolysis of both oral and parenteral administration of the
astaxanthin ester derivates, providing a reservoir of
cardioprotective agent with a significant half-life due to favorable ADME in mammals. Due to the well-documented safety profile of
astaxanthin in humans,
disodium disuccinate astaxanthin may well find clinical utility in cardiovascular applications in humans following successful completion of preclinical and clinical pharmacology and toxicology studies in animals and humans, respectively.