Ormeloxifene attenuates oxidative stress and inflammation in isoproterenol-induced cardiac hypertrophy

Menopause increases the risk of cardiovascular diseases in women, suggesting the cardioprotective effect of estrogen. However, the use of estrogen replacement therapy in this group may activate estrogen receptors in the reproductive system, increasing the risk of breast and endometrial cancers. Hence, alternative cardioprotective therapy is necessary. This study investigated the cardioprotective potential of ormeloxifene, a non-steroidal selective estrogen receptor modulator (SERM), in isoproterenol-induced cardiac hypertrophy in ovariectomized rats. Twenty-four female Sprague-Dawley rats underwent bilateral ovariectomy or sham operation and grouped into four (n = 6/group): ovary-intact control, ovariectomized control, ovariectomized + isoproterenol (10 mg/kg, sc/day) and ovariectomized + isoproterenol + ormeloxifene (2.5 mg/kg, p.o/day), and treatments continued for 28 days. Findings revealed increased inflammation, oxidative stress and mitochondrial dysfunction in isoproterenol-treated rats, resulting in apoptosis and hypertrophy. In contrast, ormeloxifene attenuated cardiac hypertrophy by reducing oxidative stress, inflammation, mitochondrial dysfunction and apoptosis. Finally, evaluation of uterine weight showed that ormeloxifene was less uterotrophic; it did not interfere with ovarian estrogen synthesis in the isoproterenol-treated ovariectomized rat and may not affect circulating estrogen. Thus, ormeloxifene may represent a novel therapeutic drug for improved cardiac function in patients with cardiovascular diseases.