Pterostilbene reduces oxidative stress, prevents hypertrophy and preserves systolic function of right ventricle in cor pulmonale model

• Published in: British journal of pharmacology Vol. 174; no. 19; pp. 3302 - 3314
• Main Authors: Santos Lacerda, Denise, Türck, Patrick, Gazzi de Lima‐Seolin, Bruna, Colombo, Rafael, Duarte Ortiz, Vanessa, Poletto Bonetto, Jéssica Hellen, Campos‐Carraro, Cristina, Bianchi, Sara Elis, Belló‐Klein, Adriane, Linck Bassani, Valquiria, Sander da Rosa Araujo, Alex
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.10.2017; John Wiley and Sons Inc
• Subjects: 2-Hydroxypropyl-beta-cyclodextrin - chemistry; 2-Hydroxypropyl-beta-cyclodextrin - pharmacology; 2-Hydroxypropyl-beta-cyclodextrin - therapeutic use; Animals; Anions; Antioxidants; Bioavailability; Cardiomegaly - prevention & control; Catalase - metabolism; Echocardiography; Glutathione Peroxidase - metabolism; Heart diseases; Heart Ventricles - drug effects; Heart Ventricles - metabolism; Hypertension, Pulmonary - drug therapy; Hypertension, Pulmonary - metabolism; Hypertension, Pulmonary - pathology; Hypertension, Pulmonary - physiopathology; Hypertrophy; Liver - drug effects; Liver - pathology; Lung - drug effects; Lung - pathology; Male; Monocrotaline; Muscle contraction; NAD(P)H oxidase; NADPH Oxidases - metabolism; Oxidative stress; Oxidative Stress - drug effects; Pathophysiology; Pulmonary hypertension; Rats, Wistar; Research Paper; Research Papers; Rodents; Stilbenes - chemistry; Stilbenes - pharmacology; Stilbenes - therapeutic use; Superoxide; Superoxide anions; Superoxide Dismutase - metabolism; Systole - drug effects; Ventricle; Ventricular Function - drug effects; β-Cyclodextrin
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/bph.13948

Background and Purpose In cor pulmonale, the increased afterload imposed on the right ventricle (RV) generates a maladaptive response, impairing the contractile cardiac function. Oxidative mechanisms play an important role in the pathophysiology and progression of this disease. The administration of pterostilbene (PTS), a phytophenol with antioxidant potential, may represent a therapeutic option. In the present study, we evaluated the effect of PTS complexed with hydroxypropyl‐β‐cyclodextrin (HPβCD) on hypertrophy, contractile function and oxidative parameters in the RV of rats with pulmonary hypertension, induced by the administration of monocrotaline (MCT). Experimental Approach The rats received daily doses of the PTS : HPβCD complex at 25, 50 or 100 mg·kg−1, p.o., for 14 days. The diastolic function, E/A ratio, and systolic function, shortening fraction, fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE) of the RV were determined by echocardiography. Key Results The PTS : HPβCD complex reduced the production of NADPH oxidase‐dependent superoxide anions and oxidative stress in the RV of MCT‐treated rats in a dose‐dependent manner. At higher doses it prevented the reduction in FAC and TAPSE in MCT‐treated animals. Conclusions and Implications The PTS : HPβCD complex prevented the maladaptative remodelling and protected systolic function in the RV of rats with pulmonary hypertension. These cardioprotective mechanisms may be related, in part, to the antioxidant potential of PTS, favoured by the increased p.o. bioavailability promoted by the presence of HPβCD in the complex.