Effect of limonene and sobrerol on monocrotaline-induced lung alterations and pulmonary hypertension.
The effects of two monocyclic monoterpenes, limonene and sobrerol, known as inhibitors of farnesyltransferase activity, were studied on monocrotaline (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 plus septum weight ratios, RV/(LV + S), were markedly increased in rats subcutaneously injected with MCT (60 mg/kg). Limonene and sobrerol, administered daily at the oral dose of 400 mg/rat, markedly decreased the MCT-induced alterations. After treatment for 21 days, limonene still prevented pulmonary hypertension and the increase in RV/(LV + S). Both monoterpenes also reduced the increase in pulmonary arterial media thickness, the development of interstitial fibrosis and the increase in the number of macrophages in intra-alveolar spaces and of lymphocytes around the pulmonary veins. The present data indicate that treatment of rats with inhibitors of farnesyltransferase, like limonene and sobrerol, regulate the development of pulmonary hypertension.
Touvay
C
C
Institut Henri Beaufour, Les Ulis, France.
Vilain
B
B
Carré
C
C
Mencia-Huerta
J M
JM
Braquet
P
P
D019883:Alkyl and Aryl Transferases; D000818:Animals; D053138:Cyclohexenes; D004353:Drug Evaluation, Preclinical; D051231:Farnesyltranstransferase; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D000077222:Limonene; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D008297:Male; D016686:Monocrotaline / Q000633:toxicity*; D009124:Muscle Proteins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000517:prevention & control*; D017368:Protein Prenylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013729:Terpenes / Q000494:pharmacology / Q000627:therapeutic use*; D014166:Transferases / Q000037:antagonists & inhibitors*
D053138:Cyclohexenes; D009124:Muscle Proteins; D013729:Terpenes; D016686:Monocrotaline; D000077222:Limonene; C003316:sobrerol; D014166:Transferases; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase