The effect of the phytoestrogen genistein on myocardial protection, preconditioning and oxidative stress.
BACKGROUND
We have previously shown that estrogen administered in ovariectomized female rabbits significantly reduce myocardial infarct size. We now investigated whether the phytoestrogen genistein similarly protects ischemic myocardium and whether this is associated with its antioxidant properties. In addition, we examined whether genistein abolishes preconditioning, since at high doses, it inhibits tyrosine kinase.


METHODS
We studied five groups of New Zealand white female rabbits. Group A (n = 12) were normal controls, group B (n = 14) were ovariectomized 4 weeks prior to the experiment, group C (n = 10) were ovariectomized and treated with genistein (0.2 mg kg(-1) day(-1) subcutaneously) for 4 weeks before the experiment, group D (n = 12) had intact gonads and were treated with genistein (0.2 mg kg(-1) day(-1) subcutaneously) for 4 weeks before the experiment and group E (n = 8) were ovariectomized 4 weeks prior to the experiment and treated with a single dose of genistein (0.2 mg kg(-1) day(-1) subcutaneously) just prior to the experiment. All animals underwent 30 min of heart ischemia and 120 min of reperfusion, with (subgroup I) or without (subgroup II) preconditioning. Malondialdehyde (MDA) concentration just before the experiment was determined.


RESULTS
We found significant differences between the groups-p < 0.0001 in factorial ANOVA. The groups with preconditioning had significant smaller infarcts compared to those without-AI vs AII (10.66 +/- 1.42% vs 43.22 +/- 2.67%), BI vs BII (18.53 +/- 2.36% vs 43.05 +/- 8.37%), CI vs CII (10.17 +/- 2.07% vs 44.5 +/- 5.47%), DI vs DII (14.98 +/- 2.36% vs 37.79 +/- 3.92%) and EI vs EII (17.11 +/- 3.24% vs 42.08 +/- 3.42%), p < 0.0005. Ovariectomy was not associated with larger myocardial infarctions-AII vs BII, p = NS. Genistein, for 4 weeks, did not protect ischemic myocardium in either ovariectomized or non-ovariectomized animals-BII vs CII and AII vs DII, p = NS. There was no significant difference between the preconditioned animals, with intact gonads or ovariectomized (AI vs BI, p = NS), ovariectomized with or without genistein (BI vs CI, p = NS) and non-ovariectomized whether treated with genistein or not (AI vs DI, p = NS). A single dose of genistein did not offer any protection (EII vs BII, p = NS), nor did it modify the preconditioning effect (EI vs BI, p = NS). We found no significant difference in MDA plasma levels between the groups.


CONCLUSIONS
Genistein, at this dose, does not reduce infarct size per se nor abolishes the protection induced by preconditioning, in both ovariectomized and non-ovariectomized animals. Preconditioning offers myocardial protection in animals with intact gonads as well as estrogen deprived; bilateral ovariectomy, at least during short-term, is not associated with larger myocardial infarcts compared to control animals. In addition estrogen deprivation, during short term, as well as genistein do not modify oxidative stress.
Sbarouni
Eftihia
E
2nd Department of Cardiology, Onassis Cardiac Surgery Center, 176 74, Athens, Greece. elbee@ath.forthnet.gr
Iliodromitis
Efstathios K
EK
Zoga
Anastasia
A
Vlachou
Georgia
G
Andreadou
Ioanna
I
Kremastinos
Dimitrios Th
DT
D000818:Animals; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D019157:Ischemic Preconditioning, Myocardial; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology*; D009206:Myocardium / Q000473:pathology; D010052:Ovariectomy; D018384:Oxidative Stress / Q000187:drug effects; D048789:Phytoestrogens / Q000494:pharmacology*; D011817:Rabbits
D048789:Phytoestrogens; D019833:Genistein