3,4,5,6-Tetrahydroxyxanthone protects against myocardial ischemia-reperfusion injury in rats.
In the present study, we tested the protective effect of 3,4,5,6-tetrahydroxyxanthone, a synthetic xanthone derivative, on myocardial ischemia-reperfusion injury in rats. Ischemia-reperfusion injury was induced by 30 min of global ischemia and 30 min of reperfusion in isolated rat hearts or 30 min coronary artery occlusion and 120 min reperfusion in vivo, respectively. Heart rate, coronary flow (CF), left ventricular pressure (LVP), and its first derivative (+/- dp/dt (max)) were recorded, and the activity of creatine kinase in coronary effluent and tumor necrosis factor-alpha (TNF-alpha) content in myocardial tissues were measured in vitro. The activity of serum creatine kinase, the level of TNF-alpha and interleukin-6 (IL-6), and myocardial infarct size were measured in vivo. 3,4,5,6-tetrahydroxyxanthone (30, 100 or 300 microM) caused a significant improvement of cardiac function (LVP and +/- dp/dt (max)) and a decrease in the release of creatine kinase in coronary effluent as well as the level of TNF-alpha in myocardial tissues in vitro. 3,4,5,6-tetrahydroxyxanthone (0.5 or 1.0 mg/kg, i.v.) also markedly decreased infarct size and the release of creatine kinase and TNF-alpha, and increased serum IL-6 level in vivo. These results suggest that 3,4,5,6-tetrahydroxyxanthone possesses a protective effect on myocardial ischemia-reperfusion injury, and that the protective effects of 3,4,5,6-tetrahydroxyxanthone may be related to inhibition of TNF-alpha production and stimulation of IL-6 generation by inhibition of ROS production.
Dai
Zhong
Z
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Xiang-Ya Road #110, Changsha, Hunan 410078, China.
Jiang
De-Jian
DJ
Hu
Gao-Yun
GY
Du
Yan-Hua
YH
Yu
Jing
J
Hu
Chang-Ping
CP
Luo
Dan
D
Li
Yuan-Jian
YJ
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D017725:Ventricular Pressure / Q000187:drug effects; D044004:Xanthones / Q000494:pharmacology*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D044004:Xanthones