Oxidative Stress and Inflammatory Mediators in Exhaled Breath Condensate of Patients with Pulmonary Tuberculosis. A Pilot Study with a Biomarker Perspective.

Silvia Guzmán-Beltrán,Claudia Carranza,Martha Torres,Esmeralda Juárez,Laura Elena Carreto-Binaghi,Yolanda Gonzalez,Marcela Muñoz-Torrico

doi:10.3390/antiox10101572

Abstract

Tuberculosis (TB) is one of the highest infectious burdens worldwide. An excess of inflammation and inadequate antioxidant defense mechanisms are believed to lead to chronic inflammation and lung damage in tuberculosis (TB). However, circulating metabolites do not always replicate lung-associated biomarkers that define the pathobiology of the disease. The objective of this study was to determine the utility of exhaled breath condensate (EBC), a non-invasive and straightforward sample, to evaluate alveolar space-derived metabolites of redox state and inflammation. We assessed the levels of exhaled oxidant/antioxidant parameters (8-isoprostane, MDA, GSH), inflammatory markers, such as nucleosomes, cytokines (IL-2, IL-4, IL-6 and IL-8, IL-10, GM-CSF, TNF-α, and IFN-γ) and lipid mediators (PGE2, LTB4, RvD1, and Mar1), in patients with recently diagnosed pulmonary TB and healthy controls’ EBC and serum. The TB patients showed 36% lower GSH levels, and 2-, 1.4-, 1.1-, and 50-fold higher levels of 8-isoprostanes, nucleosomes, IL-6, and LTB4, respectively, in EBC. There was no correlation between EBC and serum, highlighting the importance of measuring local biomarkers. Quantitation of local inflammatory molecules and redox states in EBC would help find biomarkers useful for pharmacological and follow-up studies in pulmonary tuberculosis.

Highlights

Tuberculosis (TB) is one of the highest infectious burdens worldwide (Global TB report2020)
Because eicosanoid effects may depend on their relative contribution rather than absolute levels [17], we investigated the following pro-inflammatory/pro-resolving eicosanoid ratios: prostaglandin E2 (PGE2)/RvD1, PGE2/Mar, Leukotriene B4 (LTB4)/RvD1, and LTB4/Mar1
We found that none of the eicosanoid ratios in exhaled breath condensate (EBC) distinguished the patients from the healthy subjects (Figure 4c)

Summary

Introduction

Tuberculosis (TB) is one of the highest infectious burdens worldwide (Global TB report2020). Pulmonary fibrosis and dysfunction in TB result from chronic inflammation in the lung, and inflammatory mediators such as oxygen radicals, cytokines, and eicosanoids released by immune and nonimmune cells are critical for sustaining inflammation [1,2,3,4,5]. Constant oxidative stress may contribute to the development of lung dysfunction because patients with pulmonary TB have increased circulating markers of free radical activity, some of which remain elevated even after the conclusion of antimycobacterial chemotherapy [6]. Patients with TB have elevated plasma levels of oxidative stress markers such as malondialdehyde (MDA) and conjugated dienes and decreased antioxidant effectors such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) and glutathione (GSH) [7]. Patients with TB have elevated plasma levels of oxidative stress markers such as malondialdehyde (MDA) and conjugated dienes and decreased antioxidant effectors such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) and glutathione (GSH) [7]. 4.0/).

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