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Cardioprotective effects of 5-hydroxymethylfurfural mediated by inhibition of L-type Ca2+ currents

G Wölkart1, A Schrammel1, C N Koyani2

  • 1Institute of Pharmaceutical Sciences, Department of Pharmacology and Toxicology, University of Graz, Graz, Austria.

British Journal of Pharmacology
|August 3, 2017
PubMed
Abstract

Insights

The antioxidant 5-hydroxymethylfurfural (5-HMF) shows cardioprotective effects by inhibiting L-type calcium channels, particularly during ischemia/reperfusion injury. This suggests 5-HMF could be a valuable addition to cardioplegic solutions.

Area of Science:

  • Cardiovascular Pharmacology
  • Drug Discovery
  • Biomedical Research

Background:

  • 5-hydroxymethylfurfural (5-HMF) is an antioxidant with demonstrated therapeutic potential in various experimental conditions.
  • 5-HMF is currently under investigation as a potential antisickling agent in clinical trials.
  • Understanding the cardiovascular effects of 5-HMF is crucial for its broader therapeutic applications.

Purpose of the Study:

  • To investigate the cardiovascular effects of 5-hydroxymethylfurfural (5-HMF).
  • To elucidate the underlying mechanism of action for 5-HMF's cardiovascular effects.
  • To assess the cardioprotective potential of 5-HMF in the context of ischemia/reperfusion injury.

Main Methods:

  • Vascular reactivity studies using pre-contracted porcine coronary arteries.
  • Hemodynamic assessments in isolated normoxic-perfused rat hearts.
  • Electrophysiological investigations (patch-clamp) on guinea pig ventricular cardiomyocytes to study action potentials and L-type calcium currents (ICa,L).
  • Evaluation of cardioprotective effects in isolated hearts subjected to ischemia/reperfusion (I/R) injury.

Main Results:

  • 5-HMF induced concentration-dependent relaxation of coronary arteries.
  • In isolated perfused hearts, 5-HMF exhibited negative inotropic, lusitropic, and chronotropic effects.
  • 5-HMF significantly improved the recovery of cardiac function following I/R injury.
  • Patch-clamp studies revealed that 5-HMF inhibits L-type calcium channels, affecting current density, inactivation properties, and recovery kinetics.

Conclusions:

  • 5-HMF demonstrates significant cardioprotective effects against ischemia/reperfusion injury.
  • The cardioprotective mechanism of 5-HMF involves the inhibition of L-type calcium channels.
  • 5-HMF is a promising candidate for inclusion in cardioplegic solutions for cardiac surgery.
  • Potential adverse effects and contraindications associated with calcium channel blockers must be considered for clinical use of 5-HMF.

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