Daidzein administration in vivo reduces myocardial injury in a rat ischemia/reperfusion model by inhibiting NF-kappaB activation.
OBJECTIVE
We tested the hypothesis that daidzein may reduce myocardial damage by both inhibiting the release of cytokines and limiting the nuclear translocation of NF-kappaB.


METHODS
Male Sprague-Dawley rats were anesthetized, and the left anterior descending coronary artery (LAD) was ligated for 25 min. Twenty-four hours after reperfusion was established, the hemodynamics and infarct size were examined.


RESULTS
Treatment with daidzein (10 mg/kg, i.p.) 1 h prior to the ischemia/reperfusion procedure (I/R) reduced the infarct size by 52.8% (P<0.05). Daidzein also significantly improved I/R-induced myocardial contractile dysfunction by improving the left ventricular diastolic pressure and the positive and negative maximal values of the first derivative of the left ventricular pressure. In addition, daidzein reduced the plasma levels of TNF-alpha and IL-6 in I/R rats and decreased malondialdehyde levels, myeloperoxidase activity, catalase activity and neutrophil infiltration in I/R rat myocardium. Interestingly, daidzein inhibited I/R-induced myocardial apoptosis by decreasing DNA strand breaks and cleaved caspase-3 activity. Furthermore, daidzein inhibited both the nuclear translocation of NF-kappaB in I/R rat hearts and the H(2)O(2)-induced activation of NF-kappaB-luciferase activity in human umbilical vein endothelial cells.


CONCLUSIONS
This study reveals that the administration of daidzein in vivo attenuates I/R-induced myocardial damage via inhibition of NF-kappaB activation, which in turn may suppress inflammatory cytokine expression.
Kim
Jong Woo
JW
Department of Thoracic and Cardiovascular Surgery, School of Medicine, Gyeongsang National University, Jinju, 660-751, Republic of Korea. masa-t@msic.med.osaka-cu.ac.jp
Jin
Yong Chun
YC
Kim
Young Min
YM
Rhie
Sangho
S
Kim
Hye Jung
HJ
Seo
Han Geuk
HG
Lee
Jae Heun
JH
Ha
Yeong Lae
YL
Chang
Ki Churl
KC
D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007529:Isoflavones / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015850:Interleukin-6; D007529:Isoflavones; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C004742:daidzein