Myocardial hypertrophy is prevented by farnesol through oxidative stress and ERK1/2 signaling pathways.

Abstract Farnesol is a sesquiterpene found in several plants, with multiple pharmacological activities. However, pharmacological actions of farnesol in the treatment of cardiac hypertrophy are not yet reported. This study aimed to investigate the effect and regulatory mechanisms of farnesol against isoproterenol-induced pathological cardiac hypertrophy. Male Wistar rats were treated for 8 days with isoproterenol (4.5 mg/kg; i. p.) and with farnesol (50 μM; i. p.). Hearts were subjected to evaluation of left ventricular developed pressure (LVDP), coronary pressure, electrocardiogram, histopathological analysis, reactive oxygen species (ROS) generation, antioxidant enzyme activity, and pro- and anti-apoptosis protein expression. The results showed that severe impairment of LVDP induced by cardiac hypertrophy was significantly prevented by farnesol treatment. Moreover, farnesol attenuated electrocardiographic changes that are characteristic of cardiac hypertrophy, as well as prevented the increase of fibrosis and migration of inflammatory cells in cardiac tissue. Additionally, farnesol treatment prevented the increase of cardiac ROS generation and restored the activity of endogenous antioxidant enzymes, such as SOD and catalase. It was also evidenced that farnesol decreased the ERK1/2, Bax and Caspase 3 activation, and an increase of AKT and Bcl-2 protein expression, which can be associated with the pathological cardiac remodeling and also with cardioprotection mediated by farnesol, respectively. These results suggest that farnesol is a novel therapeutic agent for amelioration of cardiac hypertrophy in rats.