TY - JOUR

T1 - Oral pre-treatment with thiocyanate (SCN-) protects against myocardial ischaemia-reperfusion injury in rats

AU - Hall, Luke

AU - Guo, Chaouri

AU - Tandy, Sarah

AU - Broadhouse, Kathryn

AU - Dona, Anthony C.

AU - Malle, Ernst

AU - Bartels, Emil D.

AU - Christoffersen, Christina

AU - Grieve, Stuart M.

AU - Figtree, Gemma

AU - Hawkins, Clare L.

AU - Davies, Michael J.

PY - 2021

Y1 - 2021

N2 - Despite improvements in revascularization after a myocardial infarction, coronary disease remains a major contributor to global mortality. Neutrophil infiltration and activation contributes to tissue damage, via the release of myeloperoxidase (MPO) and formation of the damaging oxidant hypochlorous acid. We hypothesized that elevation of thiocyanate ions (SCN-), a competitive MPO substrate, would modulate tissue damage. Oral dosing of rats with SCN-, before acute ischemia-reperfusion injury (30 min occlusion, 24 h or 4 week recovery), significantly reduced the infarct size as a percentage of the total reperfused area (54% versus 74%), and increased the salvageable area (46% versus 26%) as determined by MRI imaging. No difference was observed in fractional shortening, but supplementation resulted in both left-ventricle end diastolic and left-ventricle end systolic areas returning to control levels, as determined by echocardiography. Supplementation also decreased antibody recognition of HOCl-damaged myocardial proteins. SCN- supplementation did not modulate serum markers of damage/inflammation (ANP, BNP, galectin-3, CRP), but returned metabolomic abnormalities (reductions in histidine, creatine and leucine by 0.83-, 0.84- and 0.89-fold, respectively), determined by NMR, to control levels. These data indicate that elevated levels of the MPO substrate SCN-, which can be readily modulated by dietary means, can protect against acute ischemia-reperfusion injury.

AB - Despite improvements in revascularization after a myocardial infarction, coronary disease remains a major contributor to global mortality. Neutrophil infiltration and activation contributes to tissue damage, via the release of myeloperoxidase (MPO) and formation of the damaging oxidant hypochlorous acid. We hypothesized that elevation of thiocyanate ions (SCN-), a competitive MPO substrate, would modulate tissue damage. Oral dosing of rats with SCN-, before acute ischemia-reperfusion injury (30 min occlusion, 24 h or 4 week recovery), significantly reduced the infarct size as a percentage of the total reperfused area (54% versus 74%), and increased the salvageable area (46% versus 26%) as determined by MRI imaging. No difference was observed in fractional shortening, but supplementation resulted in both left-ventricle end diastolic and left-ventricle end systolic areas returning to control levels, as determined by echocardiography. Supplementation also decreased antibody recognition of HOCl-damaged myocardial proteins. SCN- supplementation did not modulate serum markers of damage/inflammation (ANP, BNP, galectin-3, CRP), but returned metabolomic abnormalities (reductions in histidine, creatine and leucine by 0.83-, 0.84- and 0.89-fold, respectively), determined by NMR, to control levels. These data indicate that elevated levels of the MPO substrate SCN-, which can be readily modulated by dietary means, can protect against acute ischemia-reperfusion injury.

KW - MYELOPEROXIDASE-DERIVED OXIDANTS

KW - ABSOLUTE RATE CONSTANTS

KW - C-REACTIVE PROTEIN

KW - HYPOCHLOROUS ACID

KW - HYPOTHIOCYANOUS ACID

KW - AMINO-ACIDS

KW - ATHEROSCLEROTIC PLAQUE

KW - COLLAGEN DEPOSITION

KW - CARDIAC METABOLISM

KW - THIOL OXIDATION

U2 - 10.1038/s41598-021-92142-x

DO - 10.1038/s41598-021-92142-x

M3 - Journal article

C2 - 34135432

VL - 11

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 12712

ER -