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Raloxifene is a better antioxidant of low-density lipoprotein than estradiol or tamoxifen in postmenopausal women in vitro.
Menopause. 2003 Mar-Apr; 10(2):142-6.M

Abstract

OBJECTIVE

The oxidation of low-density lipoprotein (LDL) is an important factor in the development of atherosclerosis. The antioxidant activity of some compounds buffers the free radicals generated either endogenously or exogenously, thus decreasing the potential damage mediated by oxidation. Estrogens are potent antioxidants of LDL, in vitro and in vivo, a mechanism that could probably influence the cardioprotection associated with hormone replacement therapy in postmenopause. We conducted an in vitro study of the antioxidant effect on LDL of two selective estrogen receptor modulators, raloxifene (RLX) and tamoxifen (TMX), comparing them with the known antioxidant effect of estradiol (E2).

DESIGN

LDL was isolated by ultracentrifugation from plasma obtained from 12 healthy, untreated, postmenopausal women. Aliquots containing 0.5 mg of LDL protein were incubated for 4 h with CuSO4 (15 micro M) to induce oxidative stress and with one of the three compounds studied: RLX, TMX, or E2 at doses of 0, 1, 2, 3, 5, 15, 50, and 500 micro M, and 1 and 2 mM. Malonaldehyde (MDA, nmol/mg protein) was measured as a marker of LDL oxidation.

RESULTS

E2 induced a dose-dependent decrease in MDA concentration. MDA values decreased significantly, as compared with baseline, starting at a concentration of 2 micro M for RLX and 3 micro M for both, TMX, or E2. The dose necessary to reduce the generation of MDA by 50% was significantly lower for RLX (3.3 micro M, < 0.001) than for E2 (24.6 micro M) or TMX (35.3 micro M). The area under the curve also showed a higher antioxidant activity for RLX compared with TMX or E2 (< 0.001).

CONCLUSIONS

The in vitro antioxidant activity of RLX is substantially more potent than TMX or E2. This finding, added to the other beneficial effects of the drug in the cardiovascular system, could imply some cardioprotector effect.

Authors+Show Affiliations

Department of Endocrinology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago Chile. arteaga@med.puc.clNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12627039

Citation

Arteaga, Eugenio, et al. "Raloxifene Is a Better Antioxidant of Low-density Lipoprotein Than Estradiol or Tamoxifen in Postmenopausal Women in Vitro." Menopause (New York, N.Y.), vol. 10, no. 2, 2003, pp. 142-6.
Arteaga E, Villaseca P, Bianchi M, et al. Raloxifene is a better antioxidant of low-density lipoprotein than estradiol or tamoxifen in postmenopausal women in vitro. Menopause. 2003;10(2):142-6.
Arteaga, E., Villaseca, P., Bianchi, M., Rojas, A., & Marshall, G. (2003). Raloxifene is a better antioxidant of low-density lipoprotein than estradiol or tamoxifen in postmenopausal women in vitro. Menopause (New York, N.Y.), 10(2), 142-6.
Arteaga E, et al. Raloxifene Is a Better Antioxidant of Low-density Lipoprotein Than Estradiol or Tamoxifen in Postmenopausal Women in Vitro. Menopause. 2003 Mar-Apr;10(2):142-6. PubMed PMID: 12627039.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Raloxifene is a better antioxidant of low-density lipoprotein than estradiol or tamoxifen in postmenopausal women in vitro. AU - Arteaga,Eugenio, AU - Villaseca,Paulina, AU - Bianchi,Marcelo, AU - Rojas,Auristela, AU - Marshall,Guillermo, PY - 2003/3/11/pubmed PY - 2003/6/21/medline PY - 2003/3/11/entrez SP - 142 EP - 6 JF - Menopause (New York, N.Y.) JO - Menopause VL - 10 IS - 2 N2 - OBJECTIVE: The oxidation of low-density lipoprotein (LDL) is an important factor in the development of atherosclerosis. The antioxidant activity of some compounds buffers the free radicals generated either endogenously or exogenously, thus decreasing the potential damage mediated by oxidation. Estrogens are potent antioxidants of LDL, in vitro and in vivo, a mechanism that could probably influence the cardioprotection associated with hormone replacement therapy in postmenopause. We conducted an in vitro study of the antioxidant effect on LDL of two selective estrogen receptor modulators, raloxifene (RLX) and tamoxifen (TMX), comparing them with the known antioxidant effect of estradiol (E2). DESIGN: LDL was isolated by ultracentrifugation from plasma obtained from 12 healthy, untreated, postmenopausal women. Aliquots containing 0.5 mg of LDL protein were incubated for 4 h with CuSO4 (15 micro M) to induce oxidative stress and with one of the three compounds studied: RLX, TMX, or E2 at doses of 0, 1, 2, 3, 5, 15, 50, and 500 micro M, and 1 and 2 mM. Malonaldehyde (MDA, nmol/mg protein) was measured as a marker of LDL oxidation. RESULTS: E2 induced a dose-dependent decrease in MDA concentration. MDA values decreased significantly, as compared with baseline, starting at a concentration of 2 micro M for RLX and 3 micro M for both, TMX, or E2. The dose necessary to reduce the generation of MDA by 50% was significantly lower for RLX (3.3 micro M, < 0.001) than for E2 (24.6 micro M) or TMX (35.3 micro M). The area under the curve also showed a higher antioxidant activity for RLX compared with TMX or E2 (< 0.001). CONCLUSIONS: The in vitro antioxidant activity of RLX is substantially more potent than TMX or E2. This finding, added to the other beneficial effects of the drug in the cardiovascular system, could imply some cardioprotector effect. SN - 1072-3714 UR - https://www.unboundmedicine.com/medline/citation/12627039/Raloxifene_is_a_better_antioxidant_of_low_density_lipoprotein_than_estradiol_or_tamoxifen_in_postmenopausal_women_in_vitro_ L2 - https://doi.org/10.1097/00042192-200310020-00005 DB - PRIME DP - Unbound Medicine ER -