Biochemical mechanisms and therapeutic potential of pseudohalide thiocyanate in human health

Abstract

Thiocyanate (SCN⁻) is a ubiquitous molecule in mammalian biology, reaching up to mM concentrations in extracellular fluids. Two- electron oxidation of SCN⁻ by H₂O₂ produces hypothiocyanous acid (HOSCN), a potent anti-microbial species. This reaction is catalyzed by chordate peroxidases (e.g., myeloperoxidase and lactoperoxidase), occurring in human secretory mucosa, including the oral cavity, airway, and alimentary tract, and regulates resident and transient flora as part of innate immunity. Increasing SCN⁻ levels limits the concentrations of a family of 2-electron oxidants (H₂O₂, hypohalous acids, and haloamines) in favor of HOSCN formation, altering the oxidative impact on host tissue by substitution of repairable thiol and selenol oxidations instead of biomolecule degradation. This fine-tuning of inflammatory oxidation paradoxically associates with maintained host defense and decreased host injury during infections, due in part to phylogenetic differences in the thioredoxin reductase system between mammals and their pathogens. These differences could be exploited by pharmacologic use of SCN⁻. Recent preclinical studies have identified anti-microbial and anti-inflammatory effects of SCN⁻ in pulmonary and cardiovascular animal models, with implications for treatment of infectious lung disease and atherogenesis. Further research is merited to expand on these findings and identify other diseases where SCN⁻ may be of use. High oral bioavailability and an increased knowledge of the biochemical effects of SCN⁻ on a subset of pro-inflammatory reactions suggest clinical utility.

Keywords::

• hypothiocyanous acid
• hypochlorous acid
• peroxidases
• cystic fibrosis
• redox regulation

Acknowledgements

Cystic Fibrosis Foundation Research Grant and NIH grant HL084469 to BJD.

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.