Inhibition of low-density lipoprotein and high-density lipoprotein oxidation by raloxifene.
BACKGROUND
Raloxifene (RX), a selective estrogen receptor modulator (SERM), has demonstrated hypolipidemic and in vitro antioxidant properties. In the pathogenesis of atherosclerosis, the oxidative modification of low-density lipoprotein (LDL) is implicated to play a crucial role.


METHODS
In this study, we investigated the antioxidant properties of RX during in vitro LDL and high-density lipoprotein (HDL) oxidation. The concentrations of RX, chosen ranged from 5.1 to 5100 nM. Isolated lipoproteins were supplemented with RX, and copper-mediated oxidation was monitored via the formation of conjugated dienes (CD), and oxidation resistance (lag time) was calculated. The formation of thiobarbituric acid-reactive substances (TBARS) was measured after 90, 120, 210, and 300 minutes of oxidation.


RESULTS
We found a dose-dependent inhibition of LDL and HDL oxidation in terms of both increased lag time and decreased formation of TBARS. Differences in lag time became significant at 51 nM RX added to LDL and HDL, respectively. TBARS formation in LDL was significantly reduced after 120 minutes incubation with 510 and 5100 nM RX and also after 300 minutes with 51 nM RX added. In HDL, significant reduction in TBARS formation was observed after 90 minutes by the addition of 51, 510, and 5100 nM RX.


CONCLUSIONS
These results confirm data from previous studies concerning inhibition of in vitro oxidation of LDL by RX and additionally show that RX efficiently inhibits in vitro oxidation of HDL in a broad concentration range.
Resch
Ulrike
U
Wilhelm Auerswald Atherosclerosis Research Group, Vienna, Austria.
Mellauner
Viktoria
V
Budinsky
Alexandra
A
Sinzinger
Helmut
H
D000328:Adult; D000975:Antioxidants / Q000494:pharmacology; D008076:Cholesterol, HDL / Q000187:drug effects / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects*; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013997:Time Factors
D000975:Antioxidants; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride