Regulation of lung oxidative damage by endogenous superoxide dismutase in sepsis.

Larissa Constantino,Maurício Reis Bogo,Christiane Fernandes,Cristiane Ritter,Renata Casagrande Gonçalves,Giovanna Medeiros Tavares De Oliveira,Matheus Augusto De Bittencourt Pasquali,Thais Mauad,Luiza Wilges Kist,Vinícius Renê Giombelli,Adolfo Horn,Karen V Melo,José Cláudio Fonseca Moreira,Cristiane Damiani Tomasi,Felipe Dal-Pizzol,Francieli Vuolo

doi:10.1186/2197-425x-2-17

Abstract

BackgroundThe purpose of this research is to study the relationship between superoxide dismutase (SOD) and lung redox state in an animal model of sepsis.MethodsSepsis was induced in rats by the cecal ligation and perforation model (CLP). After 3, 6, and 12 h, CLP protein content and expression of SOD1, SOD2, and SOD3 were evaluated, and SOD activity was assessed. Oxidative damage was determined by quantifying nitrotyrosine content. Lung localization of SOD3 was performed by immunohistochemistry. The protective effect of a SOD mimetic on oxidative damage, inflammation, and lung permeability was assessed 12 and 24 h after sepsis induction.ResultsLung levels of SOD1 decreased 3 and 12 h after sepsis, but SOD2 and SOD3 increased, as well as SOD activity. These alterations were not associated with changes in sod gene expression. Nitrotyrosine levels increased 3 and 12 h after sepsis. The administration of a SOD mimetic decreased nitrotyrosine and proinflammatory cytokine levels and improved lung permeability.ConclusionsSOD2 and SOD3 increased after sepsis induction, but this was insufficient to protect the lung. Treatments based on SOD mimetics could have a role in lung injury associated with sepsis.

Highlights

The purpose of this research is to study the relationship between superoxide dismutase (SOD) and lung redox state in an animal model of sepsis
Three SODs are found in mammals and regulate the concentration of superoxide: a cytosolic (SOD1), a mitochondrial (SOD2), and an extracellular (SOD3), which bind to both cell surfaces and extracellular matrices [7]. sod3 gene is highly expressed in the lung, where it plays a major protective role by controlling oxidative stress and inflammation and regulating redox homeostasis of the airways [8]
An increase in the immunocontent of SOD2 was observed at all times (Figure 2A,B,C), and there was an increase in the immunocontent of SOD3 at 6 and 12 h after sepsis induction (Figure 3A,B,C)

Summary

Introduction

The purpose of this research is to study the relationship between superoxide dismutase (SOD) and lung redox state in an animal model of sepsis. Main sources of ROS in the lung during sepsis are inflammatory cells and mitochondria [2,3]. Production of ROS leads to lipid, protein, and extracellular matrix damage, which increases pulmonary inflammation [4,5]. Sod gene is highly expressed in the lung, where it plays a major protective role by controlling oxidative stress and inflammation and regulating redox homeostasis of the airways [8]. Localization of SOD3 in the lung depends on its ability to bind to the extracellular matrix by a heparan sulfate domain, which can be fragmented by oxidative damage [5,9]. Extracellular matrix fragments stimulate inflammatory cell migration, which is of concern since matrix components are widely distributed throughout the interstitium [9]. Proteolytic cleavage of SOD3's anchorage domain alters its tissue distribution and, the oxidant/antioxidant balance [10]

Objectives

Methods

Results

Discussion

Conclusion