Hydrogen sulfide attenuates cigarette smoke-induced oxidative stress and inflammation in human primary bronchial epithelial cells and experimental COPD

Abstract

<b>Background:</b> Cigarette smoke (CS), the predominant cause of chronic obstructive pulmonary disease (COPD), induces oxidative stress (OS) and inflammation that are crucial for COPD pathogenesis. Thus, preventing CS-induced lung damage provides a novel treatment strategy against COPD. Hydrogen sulfide (H₂S), an endogenous antioxidant and anti-inflammatory molecule is reduced in the lungs of COPD patients. Inhibiting endogenous H₂S synthesis enhances inflammation, suggesting the crucial role of H₂S in lung protection. <b>Aims:</b> To investigate the potential of mitochondria targeted hydrogen sulfide donors (mtH₂SDs) in mitigating CS-induced OS and inflammation in human primary bronchial epithelial cells (hpBECs) and experimental model of COPD. <b>Methods:</b> Healthy hpBECs differentiated at the air-liquid interface were exposed to cigarette smoke extract (CSE; 10%) and treated with or without mtH₂SDs (1µM), and determined the levels of OS and proinflammatory cytokines. BALB/c mice were exposed to CS (12 cigarettes, twice/day, 5 days/week) or air for 10 weeks and treated throughout CS exposure with mtH₂SDs (1.0 mg/kg/day (intranasal)). Bronchoalveolar lavage fluid of mice was examined to determine the numbers of immune cells and levels of proinflammatory cytokines, and interstitial macrophages (IMs) were studied in lungs using flowcytometry. <b>Results:</b> MtH₂SDs significantly prevented CSE-induced increases in OS marker 4-HNE and interleukin (IL)-8 release in hpBECs, and mitigated CS-induced increases in total leukocytes, macrophages, neutrophils, tumor necrosis factor, IL-6, and IMs in mice. <b>Conclusion:</b> MtH₂SDs may be clinically useful treatment for COPD.