cardiotoxicity COX-selective inhibitors & Astaxanthin supplement

I like the Swanson brand because it passes the "smell test" and the price of
$7.79 for 60 4 mg caps seems to be a good buy. I found the Vitamin Shoppe
and Twin Labs to smell a bit too fishy for my taste although the label says
it is made from "marine algae".



jack n dalton - jackD





1: J Cardiovasc Pharmacol. 2006;47 Suppl 1:S7-14.



Rofecoxib increases susceptibility of human LDL and membrane lipids to
oxidative

damage: a mechanism of cardiotoxicity.



Mason RP, Walter MF, McNulty HP, Lockwood SF, Byun J, Day CA, Jacob RF.



Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical
School,

Boston, MA, USA. rpmason@elucidaresearch.com



Clinical investigations have demonstrated a relationship between the
extended

use of rofecoxib and the increased risk for atherothrombotic events. This
has

led to the removal of rofecoxib from the market and concern over the

cardiovascular safety of other cyclooxygenase (COX)-2 selective agents.

Experimental findings from independent laboratories now indicate that the

cardiotoxicity of rofecoxib may not be a class effect but because of its

intrinsic chemical properties. Specifically, rofecoxib has been shown to

increase the susceptibility of human low-density lipoprotein and cellular

membrane lipids to oxidative modification, a contributing factor to plaque

instability and thrombus formation. Independently of COX-2 inhibition,
rofecoxib

also promoted the nonenzymatic formation of isoprostanes and reactive
aldehydes

from biologic lipids. The basis for these observations is that rofecoxib
alters

lipid structure and readily forms a reactive maleic anhydride in the
presence of

oxygen. By contrast, other selective (celecoxib, valdecoxib) and
nonselective

(naproxen, diclofenac) inhibitors did not influence rates of low-density

lipoprotein and membrane lipid oxidation. We have now further confirmed
these

findings by demonstrating that the prooxidant activity of rofecoxib can be

blocked by the potent antioxidant astaxanthin in homochiral form (all-trans
3S,

3'S). These findings provide a mechanistic rationale for differences in

cardiovascular risk among COX-selective inhibitors because of their
intrinsic

physicochemical properties.



PMID: 16785833 [PubMed - indexed for MEDLINE]





1: Invest Ophthalmol Vis Sci. 2003 Jun;44(6):2694-701.



Effects of astaxanthin on lipopolysaccharide-induced inflammation in vitro
and in vivo.

Ohgami K, Shiratori K, Kotake S, Nishida T, Mizuki N, Yazawa K, Ohno S.

Department of Ophthalmology and Visual Sciences, Hokkaido University
Graduate

School of Medicine, Sapporo, Japan.



PURPOSE: Astaxanthin (AST) is a carotenoid that is found in marine animals
and vegetables. Several previous studies have demonstrated that AST exhibits
a wide variety of biological activities including antioxidant, antitumor,
and anti-Helicobacter pylori effects. In this study, attention was focused
on the antioxidant effect of AST. The object of the present study was to
investigate the efficacy of AST in endotoxin-induced uveitis (EIU) in rats.
In addition, the effect of AST on endotoxin-induced nitric oxide (NO),
prostaglandin E2 (PGE2), and tumor necrosis factor (TNF)-alpha production in
a mouse macrophage cell line (RAW 264.7) was studied in vitro. METHODS: EIU
was induced in male Lewis rats by a footpad injection of lipopolysaccharide
(LPS). AST or prednisolone was administered intravenously at 30 minutes
before, at the same time as, or at 30 minutes after LPS treatment. The
number of infiltrating cells and protein concentration in the aqueous humor
collected at 24 hours after LPS treatment was determined. RAW 264.7 cells
were pretreated with various concentrations of AST for 24 hours and
subsequently stimulated with 10 microg/mL of LPS for 24 hours. The levels
of PGE2, TNF-alpha, and NO production were determined in vivo and in vitro.



RESULTS: AST suppressed the development of EIU in a dose-dependent fashion.
The anti-inflammatory effect of 100 mg/kg AST was as strong as that of 10
mg/kg prednisolone. AST also decreased production of NO, activity of
inducible nitric oxide synthase (NOS), and production of PGE2 and TNF-alpha
in RAW264.7 cells in vitro in a dose-dependent manner. CONCLUSIONS: This
study suggests that AST has a dose-dependent ocular anti-inflammatory
effect, by the suppression of NO, PGE2, and TNF-alpha production, through
directly blocking NOS enzyme activity.

PMID: 12766075 [PubMed - indexed for MEDLINE]