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Comparative effects of estrogen, raloxifene and tamoxifen on endothelial dysfunction, inflammatory markers and oxidative stress in ovariectomized rats.
Life Sci. 2015 Mar 01; 124:101-9.LS

Abstract

AIM

Endothelial dysfunction is considered a premature indication of atherosclerosis and vessel damage and is present in the postmenopausal period. This study compares the influence of estrogen, raloxifene and tamoxifen on factors that affect endothelial function in ovariectomized (OVX) rats.

MAIN METHODS

The rats were divided into: SHAM; OVX; OVX+estrogen (0.5 μg/kg/day); OVX+raloxifene (2 mg/kg/day) and OVX+tamoxifen (1 mg/kg/day) groups. The acetylcholine vasorelaxation response was evaluated in the mesenteric vascular bed. The vascular oxidative stress and serum inflammatory cytokine levels were monitored, and analyses of eNOS and iNOS were performed.

KEY FINDINGS

The acetylcholine-induced responses obtained in the OVX were lower than those obtained in the SHAM, and all treatments restored this response. l-NAME reduced and equalized the acetylcholine-induced response in all groups. The attenuation of the acetylcholine-induced responses by aminoguanidine was greater in the OVX. Endothelial dysfunction in OVX was associated with oxidative stress and an increase in iNOS and decrease in eNOS expression. Except for the production of reactive oxidative species (ROS) in the OVX+tamoxifen, treatments improved the nitric oxide component of the relaxation response and normalized both the oxidative stress and the expression of those signaling pathway enzymes. Serum levels of TNF-α and IL-6 were increased in OVX, and treatments normalized these levels.

SIGNIFICANCE

Raloxifene and tamoxifen have similar anti-inflammatory effects that may be important in improving vascular dysfunction. Tamoxifen did not affect the ROS but improved endothelial dysfunction. The protective effect on endothelial function by these treatments provides evidence of their potential cardiovascular benefits in the postmenopausal period.

Authors+Show Affiliations

Department of Physiological Sciences, Center for Health Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.Department of Physiological Sciences, Center for Health Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.Department of Physiological Sciences, Center for Health Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.Department of Physiological Sciences, Center for Health Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.Department of Physiological Sciences, Center for Health Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.Nucleus of Infectious Diseases, Center for Health Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.Department of Physiological Sciences, Center for Health Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.Department of Physiological Sciences, Center for Health Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil. Electronic address: nazarebissoli@gmail.com.

Pub Type(s)

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

Language

eng

PubMed ID

25623855

Citation

Lamas, Aline Zandonadi, et al. "Comparative Effects of Estrogen, Raloxifene and Tamoxifen On Endothelial Dysfunction, Inflammatory Markers and Oxidative Stress in Ovariectomized Rats." Life Sciences, vol. 124, 2015, pp. 101-9.
Lamas AZ, Caliman IF, Dalpiaz PL, et al. Comparative effects of estrogen, raloxifene and tamoxifen on endothelial dysfunction, inflammatory markers and oxidative stress in ovariectomized rats. Life Sci. 2015;124:101-9.
Lamas, A. Z., Caliman, I. F., Dalpiaz, P. L., de Melo, A. F., Abreu, G. R., Lemos, E. M., Gouvea, S. A., & Bissoli, N. S. (2015). Comparative effects of estrogen, raloxifene and tamoxifen on endothelial dysfunction, inflammatory markers and oxidative stress in ovariectomized rats. Life Sciences, 124, 101-9. https://doi.org/10.1016/j.lfs.2015.01.004
Lamas AZ, et al. Comparative Effects of Estrogen, Raloxifene and Tamoxifen On Endothelial Dysfunction, Inflammatory Markers and Oxidative Stress in Ovariectomized Rats. Life Sci. 2015 Mar 1;124:101-9. PubMed PMID: 25623855.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative effects of estrogen, raloxifene and tamoxifen on endothelial dysfunction, inflammatory markers and oxidative stress in ovariectomized rats. AU - Lamas,Aline Zandonadi, AU - Caliman,Izabela Facco, AU - Dalpiaz,Polyana Lima Meireles, AU - de Melo,Antônio Ferreira,Jr AU - Abreu,Glaucia Rodrigues, AU - Lemos,Elenice Moreira, AU - Gouvea,Sonia Alves, AU - Bissoli,Nazaré Souza, Y1 - 2015/01/24/ PY - 2014/07/03/received PY - 2014/12/15/revised PY - 2015/01/08/accepted PY - 2015/1/28/entrez PY - 2015/1/28/pubmed PY - 2015/5/20/medline KW - Cytokines KW - Ovariectomy KW - Raloxifene KW - Tamoxifen KW - Vascular reactivity SP - 101 EP - 9 JF - Life sciences JO - Life Sci VL - 124 N2 - AIM: Endothelial dysfunction is considered a premature indication of atherosclerosis and vessel damage and is present in the postmenopausal period. This study compares the influence of estrogen, raloxifene and tamoxifen on factors that affect endothelial function in ovariectomized (OVX) rats. MAIN METHODS: The rats were divided into: SHAM; OVX; OVX+estrogen (0.5 μg/kg/day); OVX+raloxifene (2 mg/kg/day) and OVX+tamoxifen (1 mg/kg/day) groups. The acetylcholine vasorelaxation response was evaluated in the mesenteric vascular bed. The vascular oxidative stress and serum inflammatory cytokine levels were monitored, and analyses of eNOS and iNOS were performed. KEY FINDINGS: The acetylcholine-induced responses obtained in the OVX were lower than those obtained in the SHAM, and all treatments restored this response. l-NAME reduced and equalized the acetylcholine-induced response in all groups. The attenuation of the acetylcholine-induced responses by aminoguanidine was greater in the OVX. Endothelial dysfunction in OVX was associated with oxidative stress and an increase in iNOS and decrease in eNOS expression. Except for the production of reactive oxidative species (ROS) in the OVX+tamoxifen, treatments improved the nitric oxide component of the relaxation response and normalized both the oxidative stress and the expression of those signaling pathway enzymes. Serum levels of TNF-α and IL-6 were increased in OVX, and treatments normalized these levels. SIGNIFICANCE: Raloxifene and tamoxifen have similar anti-inflammatory effects that may be important in improving vascular dysfunction. Tamoxifen did not affect the ROS but improved endothelial dysfunction. The protective effect on endothelial function by these treatments provides evidence of their potential cardiovascular benefits in the postmenopausal period. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/25623855/Comparative_effects_of_estrogen_raloxifene_and_tamoxifen_on_endothelial_dysfunction_inflammatory_markers_and_oxidative_stress_in_ovariectomized_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(15)00041-7 DB - PRIME DP - Unbound Medicine ER -