The Cardioprotective Effects of Two Curcumin Derivatives on Ischemia/reperfusion Animals

• Main Authors: Fang, Chuen-Wang, 方春旺
• Other Authors: Su, Ming-Jai
• Format: Others
• Published: 2001
• Online Access: http://ndltd.ncl.edu.tw/handle/23368905094558289522

碩士 === 國立臺灣大學 === 藥理學研究所 === 89 === Abstract 1. Curcumin (diferuloyl methane) , a dietary pigment responsible for the yellow color of turmeric and curry, has many pharmacological effects including antioxidant、anti- inflammatory、anti-cancer activities. As curcumin was a potent pharmacological compound, EO161 and FN067, hetero-cyclic analogs of curcumin, were chosen to evaluate their pharmacological effects. 2. Myocardial ischemia-reperfusion represents a clinically relevant problem associated with thrombolysis, angioplasty and coronary bypass surgery. Many studies have shown that free radicals formation and ionic imbalance lead to severe cardiac injuries and harmful arrhythmias during ischemia/reperfusion. A burst of ROS generation occurs during the first minutes after ischemic tissues are reoxygenated, leading to the conclusion that the return of O2 to ischemic tissue is a critical event for the generation of ROS, especially the superoxide anion radical. Na+、Ca2+、H+ overloading and loss of K+ disturb ionic homeostasis and lead to severe arrhythmia. Administration of antioxidant or anti-arrhythmic drugs could palliate ischemia/ reperfusion injury. In this study, we compared the mechanical effects, electrophysiological properties, free radical scavenging activities and the cardioprotective effects on isolated hearts and ischemia/reperfusion animals. 3. In isolated rat right atria, EO161 and FN067 have no effects on spontaneously beating rate. EO161 suppresses the contractility slightly. Both EO161 and FN067 have no significant effects on left atria contractility. EO161 and FN067 can partially decrease right ventricle contractility in 30 μM. 4. EO161 and FN067 have more potent DPPH-radical scavenging activities than curcumin. Their IC0.2 are EO161=2.19、FN067=1.74、curcumin=9.3（μM）. 5. EO161 and FN067 have more potent superoxide anion radical scavenging activities than curcumin. Their EC50 are 1.98 μM for EO161、19.8 μM for FN067、and more than 30 μM for curcumin. EO161 is conspicuously potent than FN067 and curcumin. 6. In Langendorff perfused rat heart, EO161、FN067 and curcumin, at 30μM each, converted 90%、78%、40% of arrhythmias induced by ischemia/reperfusion respectively. 7. Whole cell voltage clamp study revealed that both EO161 and FN067 have no or little effects on INa、ICa,L、Ito. 8. In ischemia/reperfusion rat model, EO161 and FN067 (10-4~10-5g/kg) have no significant effects on mean pressure、heart rate、incidence of arrhythmia and total duration of arrhythmia in SD rat. The mortality was reduced partly by EO161 at 10-4g/kg. 9. In conclusion, EO161 and FN067 have more potent antioxidant activities than curcumin. They have similar DPPH-radical scavenging effect and EO161 has more efficacious superoxide anion scavenging activity than FN067. At 30μM, both of them do not change electrophysiology of isolated ventricular cell significantly. In isolated ischemia/ reperfusion rat heart model, the relative potency in cardioprotective activities of EO161, FN067 and curcumin is correlated well with their superoxide anion scavenging activities. Thus, EO161 and FN067 protect ischemia/ reperfusion hearts via their antioxidant but not ion channel blocking activities.