The role of sodium thiocyanate supplementation during dextran sodium sulphate-stimulated experimental colitis

Ulcerative colitis is a condition characterised by the infiltration of leukocytes into the gastrointestinal wall. Leukocyte-MPO catalyses hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN) formation from chloride (Cl - ) and thiocyanous (SCN - ) anions, respectively. While HOCl indiscriminately oxidises biomolecules, HOSCN primarily targets low-molecular weight protein thiols. Oxidative damage mediated by HOSCN may be reversible, potentially decreasing MPO-associated host tissue destruction. This study investigated the effect of SCN - supplementation in a model of acute colitis. Female mice were supplemented dextran sodium sulphate (DSS, 3% w/v) in the presence of 10 mM Cl - or SCN - in drinking water ad libitum , or with salts (NaCl and NaSCN only) or water only (controls). Behavioural studies showed mice tolerated NaSCN and NaCl-treated water with water-seeking frequency. Ion-exchange chromatography showed increased fecal and plasma SCN - levels in thiocyanate supplemented mice; plasma SCN - reached similar fold-increase for smokers. Overall there was no difference in weight loss and clinical score, mucin levels, crypt integrity and extent of cellular infiltration between DSS/SCN - and DSS/Cl - groups. Neutrophil recruitment remained unchanged in DSS-treated mice, as assessed by fecal calprotectin levels. Total thiol and tyrosine phosphatase activity remained unchanged between DSS/Cl - and DSS/SCN - groups, however, colonic tissue showed a trend in decreased 3-chlorotyrosine (1.5-fold reduction, p <0.051) and marked increase in colonic GCLC, the rate-limiting enzyme in glutathione synthesis. These data suggest that SCN - administration can modulate MPO activity towards a HOSCN-specific pathway, however, this does not alter the development of colitis within a DSS murine model. Highlights Sodium thiocyanate (SCN - ) supplementation increased plasma and fecal SCN - level. Thiocyanate supplementation diverted HOCl-mediated oxidative damage in mice colon. Thiocyanate supplementation stimulated thiol synthesis in the DSS colitis model. Thiocyanate provides no protection in an acute experimental model of UC.