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Antisclerothic effect of tibolone by reducing proinflammatory cytokines expression, ROS production and LDL-ox uptake in THP-1 macrophages.

Authors
  • Aguayo-Cerón, Karla A1
  • Gutiérrez-Iglesias, Gisela1
  • Parra-Barrera, Alberto1
  • Ocharan-Hernández, María E1
  • Romero-Nava, Rodrigo2
  • Jiménez-Zamarripa, Carlos A3
  • Calzada-Mendoza, Claudia C4
  • 1 Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional-Escuela Superior de Medicina, Ciudad de México, Mexico. , (Mexico)
  • 2 Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional-Escuela Superior de Medicina, Ciudad de México, Mexico; Hospital Infantil de México Federico Gómez, Laboratorio de Investigación en Farmacología, Ciudad de México, Mexico. , (Mexico)
  • 3 Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional-Escuela Superior de Medicina, Ciudad de México, Mexico; Hospital Psiquiátrico "Dr. Samuel Ramírez Moreno", Secretaria de Salud, Ciudad de México, Mexico. , (Mexico)
  • 4 Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional-Escuela Superior de Medicina, Ciudad de México, Mexico. Electronic address: [email protected] , (Mexico)
Type
Published Article
Journal
Steroids
Publication Date
Mar 01, 2021
Volume
167
Pages
108779–108779
Identifiers
DOI: 10.1016/j.steroids.2020.108779
PMID: 33383063
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Cardiovascular disease is more frequent in menopausal women, which has been related to factor such as weight gain, altered fat distribution, and increased inflammation markers including adipokines (MCP-1, TNF-α, IL-6) and cytokines (IL-1, IL-6, TNF-α) produced by macrophages. In addition to their phagocytic activity, macrophages secrete cytokines and chemokines that induces cell recruitment, which is a process related to vascular damage that favors the formation of atheromatous plaques. Tibolone (Tb) therapy is used to reduce the symptoms of menopause as well as osteoporosis and it has been shown to decreases the risk of fractures. To investigate the effect of tibolone in macrophage enzymatic activity, gene expression of cytokines, and its effect on foam cells formation. We use phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 cells. The cells were incubated 24 h and 48 h using pre and post-treatment schemes. We evaluated total ROS determination by NBT assay, expression of cytokines (IL-1β, IL-6, TNF-α, NOS2, ARG1, TGFβ) by RT-qPCR and foam cell formation in THP-1 differentiated macrophages stimulated with PMA. It was observed that the minor levels of total ROS determination were obtained with tibolone at 48 h in post-treatment scheme. Also, in a long term we found decrease the proinflammatory cytokines (IL-1β, IL-6 and TNF-α). Finally, with treatment for 24 h with P4 y Tb we observed fewer LDL vesicles into macrophages cytoplasm. These results suggest that tibolone reduces the inflammatory process, also inhibits the foam cells formation; suggesting a possible role in reducing cardiovascular risk. Copyright © 2020. Published by Elsevier Inc.

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