The Role of Thiocyanate in Modulating Myeloperoxidase Activity during Disease

Abstract

Thiocyanate (SCN−) is a pseudohalide anion omnipresent across mammals and is particularly concentrated in secretions within the oral cavity, digestive tract and airway. Thiocyanate can outcompete chlorine anions and other halides (F−, Br−, I−) as substrates for myeloperoxidase by undergoing two-electron oxidation with hydrogen peroxide. This forms their respective hypohalous acids (HOX where X− = halides) and in the case of thiocyanate, hypothiocyanous acid (HOSCN), which is also a bactericidal oxidative species involved in the regulation of commensal and pathogenic microflora. Disease may dysregulate redox processes and cause imbalances in the oxidative profile, where typically favoured oxidative species, such as hypochlorous acid (HOCl), result in an overabundance of chlorinated protein residues. As such, the pharmacological capacity of thiocyanate has been recently investigated for its ability to modulate myeloperoxidase activity for HOSCN, a less potent species relative to HOCl, although outcomes vary significantly across different disease models. To date, most studies have focused on therapeutic effects in respiratory and cardiovascular animal models. However, we note other conditions such as rheumatic arthritis where SCN− administration may worsen patient outcomes. Here, we discuss the pathophysiological role of SCN− in diseases where MPO is implicated.

Escherichia coli RclA is a highly active hypothiocyanite reductase

“…SCN − , the precursor of HOSCN, is found in many human secretions, with the highest reported concentrations (from 0.01 to 2 mM) in the lungs and oral cavity ( 13 ). The levels of SCN − in human fluids are dependent on diet and can be increased by consuming brassica vegetables such as broccoli or Brussels sprouts ( 14 ), as well as being present in much higher concentrations in the plasma of smokers (up to 3 mM) ( 13 , 15 ). In mammalian tissues, accumulation of SCN − acts as a chemical shield against damaging hypohalous acids ( 16 ).…”

Heme Peroxidases at Unperturbed and Inflamed Mucous Surfaces

“…Secretion of SCN − (and also I − ) from epithelial cells at the apical site occurs through several mechanisms [ 82 ]. The main focus is usually directed on two anion channels, cystic fibrosis trans-membrane conductance regulator (CFTR) and pendrin.…”

The Promising Role of Antioxidant Phytochemicals in the Prevention and Treatment of Periodontal Disease via the Inhibition of Oxidative Stress Pathways: Updated Insights

“…There is significant variation in terms of SCN − levels amongst such fluids. In a recent review, saliva was reported to exhibit the highest SCN − levels, with a range from 0.5 up to 2 mM, whereas plasma or urine SCN − concentrations were detected at the µM degree [41]. The remarkable difference of SCN − levels in saliva from those in others may be due to the presence of LPO along with other antimicrobial defenses in saliva [42].…”