Effect of ß-estradiol on hemodynamic parameters and inflammatory response during experimental sepses

• Grant number: 10/51161-6
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2010
• End date: January 31, 2013
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Angelita Maria Stabile
• Grantee: Angelita Maria Stabile
• Host Institution: Escola de Enfermagem de Ribeirão Preto (EERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Septic patients develop hypotension, which does not respond to vasopressor agents, and is usually associated with high mortality. The lipopolysaccharide (LPS) is recognized as the main trigger of this immunological response because it stimulates the production of cytokines and nitric oxide. NF-κB is a cellular transcription factor that regulates genes involved in the immunological response to LPS as the production of cytokines and NO. The activation of NF-κB is regulated by kinesis, including mitogenic activated protein kinesis (MAPKs) and AKT. The improper regulation of NF-κB is directly involved in a number of inflammatory pathologies; therefore, inhibitory agents of NF-κB activity may have relevant anti-inflammatory actions. The hormone estrogen (E2) influences the course of many inflammatory processes, affecting directly the immune system activity; however, the mechanisms underlying these effects are not entirely clear. Our hypothesis is that E2 has antiinflammatory effects during the experimental septic shock inhibiting the production of cytokines and NO by the inhibition of AKT and MAPKs pathways and, consequently, the translocation of NF-κB. Therefore, the aim of this study will be to investigate the effect of E2 on hemodynamic parameters and cytokines and NO production in vivo and in vitro, as well as the cellular pathways modulated by E2 involved in the macrophage response to LPS. We will also compare the results obtained in males and females. This study will be conducted in ovariectomized female rats and in males, treated or not acutely with LPS and in macrophage culture. (AU)