The Role of Hydrogen Sulfide in Respiratory Diseases

Abstract

Respiratory diseases are leading causes of death and disability around the globe, with a diverse range of health problems. Treatment of respiratory diseases and infections has been verified to be thought-provoking because of the increasing incidence and mortality rate. Hydrogen sulfide (H₂S) is one of the recognized gaseous transmitters involved in an extensive range of cellular functions, and physiological and pathological processes in a variety of diseases, including respiratory diseases. Recently, the therapeutic potential of H₂S for respiratory diseases has been widely investigated. H₂S plays a vital therapeutic role in obstructive respiratory disease, pulmonary fibrosis, emphysema, pancreatic inflammatory/respiratory lung injury, pulmonary inflammation, bronchial asthma and bronchiectasis. Although the therapeutic role of H₂S has been extensively studied in various respiratory diseases, a concrete literature review will have an extraordinary impact on future therapeutics. This review provides a comprehensive overview of the effective role of H₂S in respiratory diseases. Besides, we also summarized H₂S production in the lung and its metabolism processes in respiratory diseases.

Keywords: hydrogen sulfide; metabolism processes; respiratory diseases; signaling pathways.

Figure 1

A schematic diagram showing the roles of H₂S in human physiology and pathology. H₂S is formed throughout the body and moderates signaling processes in various tissues, including neuromodulation, blood pressure, injury, inflammation, anti-angiogenesis, pro-angiogenesis and sulfhydration apoptosis repair processes of the human body (H₂S: hydrogen sulfide).

Figure 2

Illustration of vascular synthesis of H₂S formed by a catalytic process in several enzymes (CSE, CBS, and 3-MSPT) in the lung. Cysteine is generated from homocysteine through transculturation pathways intervened by CBS and CSE. H₂S forms from homocysteine and cysteine via CBS and CSE. 3-MSPT forms 3-MST-cysteine persulfide (MST-SSH) using mercapto pyruvate, which is formed from cysteine via CAT. H₂S is formed from MST-SSH via a non-enzymatic reaction. H₂S is oxidized via sulfide oxidation to form thiosulfate and sulfate. H₂S is produced from thiosulfate through a non-enzymatic reaction through reductants via the catalytic activity of thiosulfate sulfurtransferase or 3-MST. H₂S: hydrogen sulfide; SQR: sulfide-quinone reductase; CBS: cystathionine beta-synthase; CSE: cystathionine γ-lyase; 3-MPST: 3-mercaptopyravute sulfurtransferase; TST: thiosulfate sulfurtransferase; CAT: cysteine aminotransferase; GSSH: glutathione.

Figure 3

The roles of H₂S in human respiratory diseases, including COPD, ALI, asthma, lung cancer, pneumonia, pulmonary edema, bronchiectasis, pulmonary fibrosis, sepsis, SAS, ARDS, lung transplantation, pulmonary hypertension and bronchopulmonary dysplasia. COPD: chronic obstructive pulmonary disease; ALI: acute lung injury; ARDS: acute respiratory distress syndrome; SAS: sleep apnea syndrome; BPD: bronchopulmonary dysplasia.

Figure 4

The signaling pathways underlying H₂S regulation of inflammation, fibrosis, apoptosis, autophagy, antioxidant activity and bronchodilation. H₂S has an anti-inflammatory outcome with diverse biological results, directly and indirectly decreasing activities such as Nrf2 activation. Abbreviations: ROS: reactive oxygen species, NF-ҝβ: nuclear factor-kappa B; Nrf2: nuclear factor erythroid-2 related factor 2; HO-1: heme oxygenase-1; PI3K: phosphoinositide 3-kinase; AMPK: AMP-activated protein kinase; ERK: extracellular signal-regulated kinase; TNF-α: tumor necrosis factor; TGF-β1: transforming growth factor-beta 1; Keap1: Kelch-like-ECH-associated protein; IL: interleukin; IKK: IҝB kinase.