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bioRxiv · 10.1101/2020.05.27.117994

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

Chami, B.·Liu, Y. A.·Burton, T.·Rayner, B. S.·Gabriel, P. S.·Shi, H.·El-Kazzi, M.·Dennis, J.·Ahmad, G.·Witting, P. K.
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Abstract

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.HighlightsSodium 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.Competing Interest StatementThe authors have declared no competing interest.AbbreviationsCDCrohn’s Disease3-Cl-Tyr3-chlorotyrosineDSSDextran Sodium SulphateGAPDHGlyceraldehyde 3-phosphate dehydrogenaseGCLCGlutamate-Cysteine Ligase Catalytic SubunitGIGastrointestinalGSHGlutathioneGSSGGlutathione DisulfideHOBrHypobromous AcidHOClHypochlorous AcidHCN-Hydrogen; CyanideHOSCNHypothiocyanous AcidIBDInflammatory Bowel DiseaseMPOMyeloperoxidaseNrf2Nuclear factor erythroid 2-related Factor 2PMNsPolymorphonuclear NeutrophilsPTPProtein Tyrosine PhosphatasesROSReactive Oxygen SpeciesSCN-ThiocyanateUCUlcerative ColitisView Full Text

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Chami, B., Liu, Y. A., Burton, T., Rayner, B. S., Gabriel, P. S., Shi, H., El-Kazzi, M., Dennis, J., Ahmad, G., Witting, P. K.. 2020-05-30. The role of sodium thiocyanate supplementation during dextran sodium sulphate-stimulated experimental colitis. https://doi.org/10.1101/2020.05.27.117994

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