Cardioprotection by the phytoestrogen genistein in experimental myocardialischaemia-reperfusion injury

1 Soybean phytoestrogens have no oestrogen agonist effects on the reproduct ive system and therefore it is reasonable to explore the potential of these naturally occurring plant oestrogens in the cardiovascular pathology. We t herefore 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 rat s were used as controls. Myocardial necrosis, myocardial myeloperoxidase ac tivity (MPO), serum creatinine phosphokinase activity (CPK), serum and macr ophage Tumour Necrosis Factor-alpha (TNF-alpha), cardiac intercellular adhe sion molecule-1 (ICAM-1) immunostaining, cardiac mRNA for ICAM-1 evaluated by the means of reverse transcriptase polymerase chain reaction (RT-PCR), v entricular arrhythmias and myocardial contractility (left ventricle dP/dt(m ax)) were evaluated. 3 Myocardial ischaemia and reperfusion in untreated rats produced marked my ocardial necrosis, increased serum CPK activity and MPO activity both in th e area-at-risk and in the necrotic area, reduced myocardial contractility, caused ventricular arrhythmias and induced a marked increase in serum and m acrophage TNF-alpha. Furthermore myocardial ischaemia-reperfusion injury in creased ICAM-1 expression in the myocardium. 4 Administration of genistein (1 mg kg(-1), i.v., 5 min after coronary arte ry occlusion) lowered myocardial necrosis and MPO activity in the area-at-r isk and in the necrotic area, decreased serum CPK activity, increased myoca rdial contractility, decreased the occurrence of ventricular arrhythmias, r educed serum and macrophages levels of TNF-alpha and blunted ICAM-1 express ion in the injured myocardium. Finally genistein added in vitro to peritone al macrophages collected from untreated rats subjected to myocardial ischae mia-reperfusion injury significantly reduced TNF-alpha production. 5 Our data suggest that genistein limits the inflammatory response and prot ects against myocardial ischaemia-reperfusion injury.