Soluble guanylate cyclase stimulation reduces oxidative stress in experimental Chronic Obstructive Pulmonary Disease.

Tanja Paul,Esther Barreiro,Anna Salazar-Degracia,Isabel Blanco,Joan A Barberà,Olga Tura-Ceide,Victor I Peinado

doi:10.1371/journal.pone.0190628

Abstract

ObjectiveSoluble guanylate cyclase (sGC) is a key enzyme of the nitric oxide–cyclic guanosine 3′,5′-monophosphate (NO–cGMP) signaling pathway, and its pharmacological stimulation has been shown to prevent the development of emphysema and pulmonary vascular remodeling in animal models of chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the effects of sGC stimulation on oxidative stress in the plasma of guinea pigs chronically exposed to cigarette smoke (CS).Methods and resultsGuinea pigs were exposed to CS or sham for three months, and received either the sGC stimulator BAY 41–2272 or vehicle. Body weight was measured weekly; and markers of oxidative stress in plasma, and airspace size and inflammatory cell infiltrate in lung tissue were analyzed at the end of the study. Compared to sham-exposed guinea pigs, CS-exposed animals gained less body weight and showed higher plasma levels of nitrated tyrosine residues (3-NT), 4-hydroxynonenal (4-HNE), and 8-hydroxydeoxyguanosine (8-OHdG). Treatment with the sGC stimulator led to a body weight gain in the CS-exposed guinea pigs similar to non-exposed and attenuated the increase in 3-NT and 4-HNE. Plasma levels of 3-NT correlated with the severity of inflammatory cell infiltrate in the lung.ConclusionStimulation of sGC prevents oxidative stress induced by CS exposure and is associated with an attenuated inflammatory response in the lung.

Highlights

Chronic obstructive pulmonary disease (COPD), which is a consequence of cigarette smoking, is one of the most common causes of chronic morbidity and death in the world [1]
Stimulation of Soluble guanylate cyclase (sGC) prevents oxidative stress induced by Cigarette smoke (CS) exposure and is associated with an attenuated inflammatory response in the lung
The present study aimed to evaluate extrapulmonary effects of sGC stimulation in guinea pigs chronically exposed to CS, a well-established experimental model of COPD [22], preventing systemic oxidative stress

Summary

Introduction

Chronic obstructive pulmonary disease (COPD), which is a consequence of cigarette smoking, is one of the most common causes of chronic morbidity and death in the world [1] It affects the respiratory system and increases the risk of systemic manifestations and serious comorbidities, such as cardiovascular disease, skeletal muscle dysfunction and cachexia [2,3]. Levels of ROS-modified proteins, lipid peroxidation, and oxidatively damaged DNA were shown to be elevated in the blood plasma of smokers and patients with COPD [12,13,14] These are biomarkers of oxidative damage to skeletal muscle proteins and organs in smokers [15]

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Conclusion