IngentaConnect 3,4,5,6-Tetrahydroxyxanthone Protects Against Myocardial Ischemia...

Authors: Zhong Dai¹; De-Jian Jiang¹; Gao-Yun Hu²; Yan-Hua Du¹; Jing Yu¹; Chang-Ping Hu¹; Dan Luo¹; Yuan-Jian Li³

Source: Cardiovascular Drugs and Therapy, Volume 18, Number 4, July 2004 , pp. 279-288(10)

Publisher: Springer

Abstract:

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

M) 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.

Keywords: 3,4,5,6-tetrahydroxyxanthone; ischemia-reperf- usion; heart; tumor necrosis factor-alpha; interleukin-6

Document Type: Research article

DOI: 10.1023/B:CARD.0000041247.95545.55

Affiliations: 1: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China 2: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China 3: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China., Email: yuan_jianli@yahoo.com

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3,4,5,6-Tetrahydroxyxanthone Protects Against Myocardial Ischemia-Reperfusion Injury in Rats