Beneficial effects of fenofibrate in pulmonary hypertension in rats

• Published in: Molecular and cellular biochemistry Vol. 449; no. 1-2; pp. 185 - 194
• Main Authors: Galhotra, Palak, Prabhakar, Pankaj, Meghwani, Himanshu, Mohammed, Soheb A., Banerjee, Sanjay Kumar, Seth, Sandeep, Hote, Milind P., Reeta, K. H., Ray, Ruma, Maulik, Subir Kumar
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2018; Springer Nature B.V
• Subjects: Animals; Aorta; BAX gene; Biochemistry; Biomedical and Life Sciences; Blood pressure; Cardiology; Echocardiography; Ejection; Female; Fenofibrate; Fenofibrate - pharmacology; Fenofibrate - therapeutic use; Gene expression; Heart; Histopathology; Hypertension; Hypertension, Pulmonary - chemically induced; Hypertension, Pulmonary - drug therapy; Hypertension, Pulmonary - metabolism; Hypertension, Pulmonary - physiopathology; Hypertrophy; Inflammation; Inflammation - drug therapy; Life Sciences; Lungs; Medical Biochemistry; Monocrotaline; Monocrotaline - toxicity; NAD(P)H oxidase; Oncology; Outflow; Oxidative stress; Oxidative Stress - drug effects; Parameters; Proteins; Pulmonary arteries; Pulmonary artery; Pulmonary hypertension; Rats; Rats, Wistar; Reactive oxygen species; Rodents; Sildenafil; Systolic pressure; Ventricle; Wall thickness; Oxidative stress; PPAR α agonist; Inflammation; Monocrotaline
• DOI: 10.1007/s11010-018-3355-3
• ISSN: 0300-8177

Pulmonary hypertension (PH) is a morbid complication of cardiopulmonary as well as several systemic diseases in humans. It is rapidly progressive and fatal if left untreated. In the present study, we investigated the effect of PPARα agonist fenofibrate (FF) on monocrotaline (MCT)-induced PH in rats. FF, because of its pleiotropic property, could be helpful in reducing inflammation, oxidative stress, and reactive oxygen species. On day 1, MCT (50 mg/kg, s.c.) was given to all the rats in MCT, sildenafil, and FF group except normal control rats. After 3 days of giving MCT, sildenafil (175 µg/kg, orally) and FF (120 mg/kg, orally) were given for 25 days. Echocardiography, hemodynamic parameters, fulton’s index, histopathology, oxidative stress parameters, inflammatory markers, Bcl2/Bax gene expression ratio in the right ventricle, and protein expression for NOX-1 in lungs were studied in all the groups. FF has shown to prevent decrease in ratio of pulmonary artery acceleration time to ejection time, increase in ratio of right ventricular outflow tract dimension to aortic outflow dimension, rise in right ventricular systolic pressure, right ventricular hypertrophy, increase in the percentage medial wall thickness (%MWT), increase in oxidative stress and inflammation, increase in NADPH oxidase-1 (NOX-1) expression, and decrease in mRNA expression of Bcl2/Bax ratio caused by MCT. To conclude, FF prevented MCT-induced PH in rats by various mechanisms. It might be helpful in preventing PH in patients who are likely to develop PH.