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 -