EFFECT OF LIMONENE AND SOBREROL ON MONOCROTALINE-INDUCED LUNG ALTERATIONS AND PULMONARY-HYPERTENSION

The effects of two monocyclic monoterpenes, limonene and sobrerol, kno wn as inhibitors of farnesyltransferase activity, were studied on mono crotaline (MCT)-induced lung injury, pulmonary hypertension and right ventricular hypertrophy in male Wistar rats. After 14 days, pulmonary arterial pressure values and the right ventricle to left ventricle plu s septum weight ratios, RV/(LV+S), were markedly increased in rats sub cutaneously injected with MCT (60 mg/kg). Limonene and sobrerol, admin istered daily at the oral dose of 400 mg/rat, markedly decreased the M CT-induced alterations. After treatment for 21 days, limonene still pr evented pulmonary hypertension and the increase in RV/(LV+S). Both mon oterpenes also reduced the increase in pulmonary arterial media thickn ess, the development of interstitial fibrosis and the increase in the number of macrophages in intra-alveolar spaces and of lymphocytes arou nd the pulmonary veins. The present data indicate that treatment of ra ts with inhibitors of farnesyltransferase, like limonene and sobrerol, regulate the development of pulmonary hypertension.