Simvastatin (SIM) is a
lipid-soluble inhibitor of hydroxy-3-methylglutaryl
coenzyme A reductase with multiple reported therapeutic benefits. The present study was designed to investigate the effect of pretreatment with SIM on
isoproterenol (ISO)-induced
cardiac hypertrophy in rats. Twenty-four male albino Wistar rats weighing 180-200 g were divided into four groups. Groups I and III received
normal saline while groups II and IV received SIM (10 mg/kg
body weight) for 30 days per gavage. In the last 7 days, rats of groups III and IV were administered ISO (5 mg/kg) intraperitoneally to induce
cardiac hypertrophy. Administration of ISO induced an increase in heart-to-
body weight (HW/BW) ratio, an increase in serum
interleukin-6, and elevated systolic and diastolic blood pressure. Serum levels of
lipids, cardiovascular risk indices, and cardiac
troponin I and
creatine phosphokinase-MB showed significant increase in ISO-induced hypertrophic rats. Histopathological examination of heart tissue revealed focal areas of subendocardium degeneration, mononuclear cellular infiltrations, fibrous tissue deposition, and increased thickness of the myocardium of left ventricle. In addition, ISO-administered rats exhibited significant upregulation of cardiac
Janus kinase, phosphorylated signal transducer and activator of transcription, and
nuclear factor-kappa B. Pretreatment with SIM significantly prevented ISO-induced
cardiac hypertrophy, alleviated the altered biochemical parameters, and improved the heart architecture. In conclusion, our study provides evidence that SIM prevented the development of
cardiac hypertrophy via modulation of the
Janus kinase/signal transducer and activator of transcription-signaling pathway in the heart of ISO-administered animals.