PMID- 10588923
OWN - NLM
STAT- MEDLINE
DCOM- 20000302
LR  - 20240315
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 128
IP  - 8
DP  - 1999 Dec
TI  - Cardioprotection by the phytoestrogen genistein in experimental myocardial 
      ischaemia-reperfusion injury.
PG  - 1683-90
AB  - 1. Soybean phytoestrogens have no oestrogen agonist effects on the reproductive 
      system and therefore it is reasonable to explore the potential of these naturally 
      occurring plant oestrogens in the cardiovascular pathology. We therefore 
      investigated the effects of genistein in a rat model of myocardial 
      ischaemia-reperfusion injury. 2. Anaesthetized rats were subjected to total 
      occlusion (45 min) of the left main coronary artery followed by 5 h reperfusion 
      (MI/R). Sham operated rats were used as controls. Myocardial necrosis, myocardial 
      myeloperoxidase activity (MPO), serum creatinine phosphokinase activity (CPK), 
      serum and macrophage Tumour Necrosis Factor-alpha (TNF-alpha), cardiac 
      intercellular adhesion molecule-1 (ICAM-1) immunostaining, cardiac mRNA for 
      ICAM-1 evaluated by the means of reverse transcriptase polymerase chain reaction 
      (RT - PCR), ventricular arrhythmias and myocardial contractility (left ventricle 
      dP/dt(max)) were evaluated. 3. Myocardial ischaemia and reperfusion in untreated 
      rats produced marked myocardial necrosis, increased serum CPK activity and MPO 
      activity both in the area-at-risk and in the necrotic area, reduced myocardial 
      contractility, caused ventricular arrhythmias and induced a marked increase in 
      serum and macrophage TNF-alpha. Furthermore myocardial ischaemia-reperfusion 
      injury increased ICAM-1 expression in the myocardium. 4. Administration of 
      genistein (1 mg kg(-1), i.v., 5 min after coronary artery occlusion) lowered 
      myocardial necrosis and MPO activity in the area-at-risk and in the necrotic 
      area, decreased serum CPK activity, increased myocardial contractility, decreased 
      the occurrence of ventricular arrhythmias, reduced serum and macrophages levels 
      of TNF-alpha and blunted ICAM-1 expression in the injured myocardium. Finally 
      genistein added in vitro to peritoneal macrophages collected from untreated rats 
      subjected to myocardial ischaemia-reperfusion injury significantly reduced 
      TNF-alpha production. 5. Our data suggest that genistein limits the inflammatory 
      response and protects against myocardial ischaemia-reperfusion injury.
FAU - Deodato, B
AU  - Deodato B
AD  - Institute of Pharmacology, School of Medicine, University of Messina, Torre 
      Biologica, Policlinico Universitario, Via C. Valeria, Gazzi, 98125 Messina, 
      Italy.
FAU - Altavilla, D
AU  - Altavilla D
FAU - Squadrito, G
AU  - Squadrito G
FAU - Campo, G M
AU  - Campo GM
FAU - Arlotta, M
AU  - Arlotta M
FAU - Minutoli, L
AU  - Minutoli L
FAU - Saitta, A
AU  - Saitta A
FAU - Cucinotta, D
AU  - Cucinotta D
FAU - Calapai, G
AU  - Calapai G
FAU - Caputi, A P
AU  - Caputi AP
FAU - Miano, M
AU  - Miano M
FAU - Squadrito, F
AU  - Squadrito F
LA  - eng
PT  - Journal Article
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Cardiovascular Agents)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - DH2M523P0H (Genistein)
RN  - EC 1.11.1.7 (Peroxidase)
RN  - EC 2.7.3.2 (Creatine Kinase)
SB  - IM
MH  - Animals
MH  - Cardiovascular Agents/*therapeutic use
MH  - Creatine Kinase/drug effects/metabolism
MH  - Female
MH  - Genistein/*therapeutic use
MH  - Intercellular Adhesion Molecule-1/drug effects/metabolism
MH  - Myocardial Ischemia/*drug therapy/metabolism
MH  - Myocardial Reperfusion Injury/*drug therapy/metabolism
MH  - Ovariectomy
MH  - Peroxidase/drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tumor Necrosis Factor-alpha/drug effects/metabolism
MH  - Ventricular Function, Left/drug effects
PMC - PMC1571810
EDAT- 1999/12/10 09:00
MHDA- 2000/03/04 09:00
PMCR- 2000/12/01
CRDT- 1999/12/10 09:00
PHST- 1999/12/10 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 1999/12/10 09:00 [entrez]
PHST- 2000/12/01 00:00 [pmc-release]
AID - 0702973 [pii]
AID - 10.1038/sj.bjp.0702973 [doi]
PST - ppublish
SO  - Br J Pharmacol. 1999 Dec;128(8):1683-90. doi: 10.1038/sj.bjp.0702973.