Efeito do galato de octila e da sinvastatina em modelos experimentais inflamatórios pulmonar e hepático: um estudo in vitro e in vivo

Abstract

Chronic inflammation is considered one of the most common reactions of the organism and occurs as a consequence of the pathogenic agent permanence which was not eliminated by acute inflammation mechanism. The uncontrollable inflammatory response of the individual can lead to sepsis. Sepsis is a complex inflammatory syndrome and it represents a grave epidemiologic problem to health systems in the whole world. The lung is the one of the main organs affected in septic patients that shows organic disorder functions. Therefore, the lung becomes an essential target to search novel therapies. The aim of this study was to evaluate the octyl gallate (OG) effect and its possible action mechanism in the sepsis treatment and acute lung injury (ALI) and the protective effect of simvastatin (SV) in mice with ALI and in cirrhotic rats submitted to the LPS action. Firstly, our “in vitro” results demonstrated that GO inhibits the release of reactive oxygen species (ROS), the neutrophil extracellular traps formation and reduces the LPS effects on apoptosis of human neutrophils. However, when we evaluated its action in an in vivo model of sepsis in mice, the treatment did not reduce the mortality caused by sepsis. Our second study showed that GO has an anti-inflammatory action in an “in vitro” model using LPS-activated RAW 264.7 alveolar macrophages. Treatment decreased the expression of inflammatory markers such as nitric oxide synthase (iNOS), interleukin-6 (IL-6) and interleukin-1β (IL-1β). When assessing GO action in mice with ALI, the treatment decreased the migration of inflammatory cells, the inflammatory cytokines production and protected the tissue against oxidative stress. When we evaluated the SV action, we observed that the drug decreased inflammatory markers, such as iNOS, IL-1β, and IL-6 in alveolar macrophages activated with LPS. The SV treatment reduced the lung injury, the migration of inflammatory cells, and the inflammatory cytokines expression in mice with ALI. SV also protected the liver from systemic inflammation caused by LPS. LPS caused dysfunction of hepatic microvasculature and decreased survival of cirrhotic animals and, SV prevented these changes probably by reducing oxidative stress.