Raloxifene does not prevent fibrinogen oxidation in vitro.
BACKGROUND
Modification of proteins may play a central role in a great variety of pathophysiological processes. It has already been ascertained that raloxifene (LY 139481), a selective estrogen receptor modulator (SERM), is an effective inhibitor of LDL oxidation. Therefore, we examined potential anti-oxidant activity related to the oxidation of the glycoprotein fibrinogen.


METHODS
In this study we investigated whether raloxifene is able to inhibit in vitro iron-mediated oxidation of fibrinogen. We tested three different concentrations of raloxifene (5, 10, and 125 microM) corresponding to the usual dosage in postmenopausal women of between 10 and 300 mg/day, choosing two incubation periods (60 and 120 min).


RESULTS
Our results in the examined dose-range provide no evidence that raloxifene is able to prevent iron-induced fibrinogen oxidation in vitro. Considering the chemical structure of the glycoprotein fibrinogen, it is likely that raloxifene is unable to attack a particle without lipophilic properties, although the site of its action on LDL is still unknown.


CONCLUSIONS
Our data suggest that raloxifene, in contrast to its effect on LDL, lacks the capability to inhibit the oxidation of fibrinogen. The biological relevance of this finding still needs to be assessed in vivo.
Blasbichler
Margit
M
Institute for Diagnosis and Treatment of Atherosclerosis and Lipid Disorders (ATHOS), Vienna, Austria.
Arakil-Aghajanian
Arsineh
A
Sinzinger
Helmut
H
D000975:Antioxidants / Q000737:chemistry*; D005340:Fibrinogen / Q000737:chemistry*; D007501:Iron / Q000737:chemistry; D010084:Oxidation-Reduction; D020849:Raloxifene Hydrochloride / Q000737:chemistry*
D000975:Antioxidants; D020849:Raloxifene Hydrochloride; D005340:Fibrinogen; D007501:Iron