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Beneficial effects of fenofibrate in pulmonary hypertension in rats

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Abstract

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.

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Acknowledgements

We are grateful to the Indian Council of Medical Research (ICMR), New Delhi, India, for providing financial support to carry out this research work.

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Authors and Affiliations

  1. Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Room No. 4017, Ansari Nagar, New Delhi, 110029, India

    Palak Galhotra, Pankaj Prabhakar, Himanshu Meghwani, K. H. Reeta & Subir Kumar Maulik

  2. Department of Cardiology, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India

    Sandeep Seth

  3. Department of Cardiothoracic and Vascular Surgery, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India

    Milind P. Hote

  4. Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India

    Ruma Ray

  5. Department of Drug Discovery Research Center (DDRC), Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana, 121001, India

    Soheb A. Mohammed & Sanjay Kumar Banerjee

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  1. Palak Galhotra
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  2. Pankaj Prabhakar
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Galhotra, P., Prabhakar, P., Meghwani, H. et al. Beneficial effects of fenofibrate in pulmonary hypertension in rats. Mol Cell Biochem 449, 185–194 (2018). https://doi.org/10.1007/s11010-018-3355-3

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