Antiarrhythmogenic and Antioxidant Effect of the Flavonoid Dioclein in a Model of Cardiac Ischemia/Reperfusion

Abstract

The antiarrhythmogenic effect of the flavonoid dioclein on myocardial ischemia/reperfusion was investigated in isolated perfused rat hearts. Low concentrations of dioclein (30 - 300 nM) induced a reduction of arrhythmias observed during the reperfusion period. Dioclein also preserved the diastolic tension after reperfusion without affecting the systolic tension. In addition, dioclein (150 nM) dramatically reduced the formation of reactive oxygen species (ROS) observed during reperfusion in hearts. In conclusion, dioclein acts as a potent antiarrhythmogenic and antioxidant drug with an excellent protective effect during reperfusion of ischemic hearts.

Flavonoids - arrhythmia - ischemia - reperfusion - antioxidant

References

• 1 Zipes D P, Wellens H J. Sudden cardiac death.  Circulation. 1998;  98 2334-51
• 2 Becker L B. New concepts in reactive oxygen species and cardiovascular reperfusion physiology.  Cardiovasc Res. 2004;  61 461-70
• 3 Dhalla N S, Elmoselhi A B, Hata T, Makino N. Status of myocardial antioxidants in ischemia-reperfusion injury.  Cardiovasc Res. 2000;  47 446-56
• 4 Jeroudi M O, Hartley C J, Bolli R. Myocardial reperfusion injury: role of oxygen radicals and potential therapy with antioxidants.  Am J Cardiol. 1994;  73 2B-7B
• 5 Sanguinetti M C, Bennett P B. Antiarrhythmic drug target choices and screening.  Circ Res. 2003;  93 491-9
• 6 Geleijnse J M, Launer L J, van der Kuip D A, Hofman A, Witteman J C. Inverse association of tea and flavonoid intakes with incident myocardial infarction: the Rotterdam study.  Am J Clin Nutr. 2002;  75 880-6
• 7 Knekt P, Kumpulainen J, Jarvinen R, Rissanen H, Heliovaara M, Reunanen A. et al . Flavonoid intake and risk of chronic diseases.  Am J Clin Nutr. 2002;  76 560-8
• 8 Seigneur M, Bonnet J, Dorian B, Benchimol D, Drouillet F, Gouverneur G. et al . Effect of the consumption of alcohol, white wine, and red wine on platelets function and serum lipids.  J Appl Cardiol. 1990;  5 215-22
• 9 Aviram M, Fuhrman B. Polyphenolic flavonoids inhibit macrophage-mediated oxidation of LDL and attenuate atherogenesis.  Atherosclerosis. 1998;  137 S45-50
• 10 De Celle T, Heeringa P, Strzelecka A E, Bast A, Smits J F, Janssen B J. Sustained protective effects of 7-monohydroxyethylrutoside in an in vivo model of cardiac ischemia-reperfusion.  Eur J Pharmacol. 2004;  494 205-12
• 11 Stanley L L, Mazier M JP. Potential explanations for the French paradox.  Nutr Res. 1999;  19 3-15
• 12 Bhattacharya J, Batista J S, Almeida R N. Dioclein, a flavanone from the roots of Dioclea grandiflora .  Phytochemistry. 1995;  38 277-8
• 13 Almeida A P, Cortes S F, Ferreira A J, Lemos V S. Increase on the coronary flow induced by dioclein in isolated rat heart.  Life Sci. 2002;  70 1121-8
• 14 Cortes S F, Rezende B A, Corriu C, Medeiros I A, Teixeira M M, Lopes M J. et al . Pharmacological evidence for the activation of potassium channels as the mechanism involved in the hypotensive and vasorelaxant effect of dioclein in rat small resistance arteries.  Br J Pharmacol. 2001;  133 849-58
• 15 Lemos V S, Freitas M R, Muller B, Lino Y D, Queiroga C E, Cortes S F. Dioclein, a new nitric oxide- and endothelium-dependent vasodilator flavonoid.  Eur J Pharmacol. 1999;  386 41-6
• 16 Bernauer W, Ernenputsch I. Antagonistic effects of alpha-adrenoceptor blocking agents on arrhythmias, enzyme release, and myocardial necrosis in isolated rat hearts with coronary occlusion and reperfusion.  Naunyn Schmiedebergs Arch Pharmacol. 1988;  338 88-95
• 17 Mueller S. Sensitive and nonenzymatic measurement of hydrogen peroxide in biological systems.  Free Radic Biol Med. 2000;  29 410-5
• 18 Spearing P, Majetich G, Bhattacharyya J. Synthesis of (R,S)-dioclein, a bioactive flavanone from the root bark of Dioclea grandiflora .  J Nat Prod. 1997;  60 399-400
• 19 Ferreira A J, Santos R A, Almeida A P. Angiotensin-(1 - 7): cardioprotective effect in myocardial ischemia/reperfusion.  Hypertension. 2001;  38 665-8
• 20 Piper H M, Abdallah Y, Schafer C. The first minutes of reperfusion: a window of opportunity for cardioprotection.  Cardiovasc Res. 2004;  61 365-71
• 21 Garcia-Dorado D, Theroux P, Duran J M, Solares J, Alonso J, Sanz E. et al . Selective inhibition of the contractile apparatus. A new approach to modification of infarct size, infarct composition, and infarct geometry during coronary artery occlusion and reperfusion.  Circulation. 1992;  85 1160-74
• 22 Siegmund B, Klietz T, Schwartz P, Piper H M. Temporary contractile blockade prevents hypercontracture in anoxic-reoxygenated cardiomyocytes.  Am J Physiol. 1991;  260 H426-35
• 23 Dixon I M, Kaneko M, Hata T, Panagia V, Dhalla N S. Alterations in cardiac membrane Ca²⁺ transport during oxidative stress.  Mol Cell Biochem. 1990;  99 125-33
• 24 Schafer C, Ladilov Y, Inserte J, Schafer M, Haffner S, Garcia-Dorado D. et al . Role of the reverse mode of the Na⁺/Ca²⁺ exchanger in reoxygenation-induced cardiomyocyte injury.  Cardiovasc Res. 2001;  51 241-50
• 25 Temsah R M, Netticadan T, Chapman D, Takeda S, Mochizuki S, Dhalla N S. Alterations in sarcoplasmic reticulum function and gene expression in ischemic-reperfused rat heart.  Am J Physiol. 1999;  277 H584-94
• 26 Ma X L, Lopez B L, Liu G L, Christopher T A, Ischiropoulos H. Peroxynitrite aggravates myocardial reperfusion injury in the isolated perfused rat heart.  Cardiovasc Res. 1997;  36 195-204
• 27 Radi R, Beckman J S, Bush K M, Freeman B A. Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide.  Arch Biochem Biophys. 1991;  288 481-7
• 28 Li X L, Li Y Q, Yan W M, Li H Y, Xu H, Zheng X X. et al . A study of the cardioprotective effect of breviscapine during hypoxia of cardiomyocytes.  Planta Med. 2004;  70 1039-44
• 29 Shao Z H, van den Hoek T L, Qin Y, Becker L B, Schumacker P T, Li C Q. et al . Baicalein attenuates oxidant stress in cardiomyocytes.  Am J Physiol. 2002;  282 H999-1006