Beneficial role of tamoxifen in isoproterenol-induced myocardial infarction.

Abstract

ER-α and ER-β agonist 17β-estradiol is reported to attenuate cardiac hypertrophy. Tamoxifen is a selective estrogen receptor modulator. Hence, the objective of this study was to investigate the effects of tamoxifen in myocardial infarction. For this, tamoxifen was administered to Sprague-Dawley rats for 1-14 days, and isoproterenol (ISO) (100 mg·(kg body mass)(-1)·day(-1)) was administered subcutaneously on the 13th and 14th days of the study in order to induce myocardial infarction, after which, various biochemical, cardiac, and morphometric parameters were evaluated. ISO produced significant dyslipidemia, hypertension, bradycardia, oxidative stress, and an increase in serum cardiac markers. Treatment with tamoxifen significantly controlled dyslipidemia, hypertension, bradycardia, oxidative stress, and reduced serum cardiac markers. The ISO control rats exhibited significant increases in the infarct size of the left ventricle (LV), LV cavity area, cardiac and LV hypertrophic indices, LV-wall thickness, cardiomyocyte diameter, and area. Treatment with tamoxifen significantly reduced infarction as well as hypertrophic and morphometric parameters. ISO also produced significant increases in the LV collagen level, decreases in Na(+)K(+) ATPase activity, and a reduction in the rate of pressure development and decay, which were prevented by tamoxifen treatment. The protective effect of tamoxifen on myocardial infarct was further confirmed by histopathological examination. Our data thus suggest that tamoxifen exerts beneficial effects in ISO-induced myocardial infarction.