Effects of acute and 2-day genistein treatment on cardiac function and ischemic tolerance in ovariectomized rats.
BACKGROUND
Genistein, a naturally occurring isoflavonic phytoestrogen associated with reduced incidence of heart disease, may be a possible alternative treatment for postmenopausal women with heart disease.


OBJECTIVE
This study examined the effects of genistein on in vitro heart function and ischemic tolerance in ovariectomized (OVX) Sprague-Dawley rats.


METHODS
To examine the acute effects of genistein on cardiac function, isolated working hearts were perfused under aerobic conditions with increasing concentrations of genistein (10-150 microM). A separate group of OVX rats was used to assess ischemic tolerance: treated rats received genistein (250 mg/kg, dissolved in 200 microL dimethyl sulfoxide [DMSO]) injected once daily for 2 days, and control rats received DMSO only. After treatment, hearts were perfused for 30 minutes under aerobic conditions and then subjected to 20 minutes of global no-flow ischemia by clamping the preload and afterload lines, followed by 30 minutes of reperfusion.


RESULTS
Genistein was associated with improvements in mechanical function in OVX rat hearts (n = 5) with maximum increases in contractility (259 mm Hg/sec above baseline) and cardiac output (7 mL/min above baseline) observed with 30 microM of genistein (both, P < 0.05). Relative to baseline, genistein-treated hearts (n = 5) also had greater ischemic tolerance than did control hearts (n = 6) and significant improvements in mean (SEM) recovery of contractility (to 75.0% [9.7%] of preischemic function; P < 0.05) and cardiac output (to 48.8% [12.3%] of preischemic function; P < 0.05) after reperfusion. These effects occurred without significant changes in myocardial levels of nonprotein thiols or thiobarbituric acid reactive substances, although a reduction in mean glucose transporter protein 4 content (13.2% [2.7%]; P < 0.05) was observed in genistein-treated hearts. No significant changes in blood pressure were observed with genistein.


CONCLUSIONS
Despite the lack of significant changes in physical characteristics, 2-day treatment with genistein was associated with significant cardioprotective effects in OVX rats, suggesting a potential therapeutic role in postmenopausal women.
Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, Arizona 85308, USA. lalnak@midwestern.edu
Layla
L
Al-Nakkash
Brandon
B
Markus
Kirk
K
Bowden
Lyn M
LM
Batia
Walter C
WC
Prozialeck
Tom L
TL
Broderick
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D019833:Genistein / Q000008:administration & dosage*; D066298:In Vitro Techniques; D007511:Ischemia / Q000188:drug therapy*; D009200:Myocardial Contraction / Q000187:drug effects*; D010052:Ovariectomy; D048789:Phytoestrogens / Q000008:administration & dosage*; D017698:Postmenopause / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D048789:Phytoestrogens; D019833:Genistein