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

Luke Hall, Chaouri Guo, Sarah Tandy, Kathryn Broadhouse, Anthony C. Dona, Ernst Malle, Emil D. Bartels, Christina Christoffersen, Stuart M. Grieve, Gemma Figtree, Clare L. Hawkins, Michael J. Davies*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

10 Citations (Scopus)
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Abstract

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.

Original languageEnglish
Article number12712
JournalScientific Reports
Volume11
Issue number1
Number of pages18
ISSN2045-2322
DOIs
Publication statusPublished - 2021

Keywords

  • MYELOPEROXIDASE-DERIVED OXIDANTS
  • ABSOLUTE RATE CONSTANTS
  • C-REACTIVE PROTEIN
  • HYPOCHLOROUS ACID
  • HYPOTHIOCYANOUS ACID
  • AMINO-ACIDS
  • ATHEROSCLEROTIC PLAQUE
  • COLLAGEN DEPOSITION
  • CARDIAC METABOLISM
  • THIOL OXIDATION

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