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Ameliorative role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats

Published online by Cambridge University Press:  06 June 2014

Amrit Pal Singh ,
Randhir Singh  and
Pawan Krishan
Amrit Pal Singh
Affiliation:
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, India
Randhir Singh*
Affiliation:
Department of Pharmacology, Maharishi Markandeshwar College of Pharmacy, Maharishi Markandeshwar University, Mullana, Ambala 133207, India
Pawan Krishan
Affiliation:
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India
*
Correspondence to: Dr R. Singh, M Pharm, PhD, Associate Professor, Department of Pharmacology, Maharishi Markandeshwar College of Pharmacy, Maharishi Markandeshwar University, Mullana, Ambala 133207, India. Tel: +91-9896029234; Fax: +91-1731-274375; E-mail: dahiya_rsd@rediffmail.com
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Abstract

Fibrates are peroxisome proliferator-activated receptor-α agonists and are clinically used for treatment of dyslipidemia and hypertriglyceridemia. Fenofibrate is reported as a cardioprotective agent in various models of cardiac dysfunction; however, limited literature is available regarding the role of gemfibrozil as a possible cardioprotective agent, especially in a non-obese model of cardiac remodelling. The present study investigated the role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats. Cardiac hypertrophy was induced by partial abdominal aortic constriction in rats and they survived for 4 weeks. The cardiac hypertrophy was assessed by measuring left ventricular weight to body weight ratio, left ventricular wall thickness, and protein and collagen content. The oxidative stress in the cardiac tissues was assessed by measuring thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The haematoxylin–eosin and picrosirius red staining was used to observe cardiomyocyte diameter and collagen deposition, respectively. Moreover, serum levels of cholesterol, high-density lipoproteins, triglycerides, and glucose were also measured. Gemfibrozil (30 mg/kg, p.o.) was administered since the first day of partial abdominal aortic constriction and continued for 4 weeks. The partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy are indicated by significant change in various parameters used in the present study that were ameliorated with gemfibrozil treatment in rats. No significant change in serum parameters was observed between various groups used in the present study. It is concluded that gemfibrozil ameliorates partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy and in rats.

Keywords

Cardiac hypertrophygemfibroziloxidative stresspartial abdominal aortic constrictionrats
Type
Original Articles
Information
Cardiology in the Young , Volume 25 , Issue 4 , April 2015 , pp. 725 - 730
Copyright
© Cambridge University Press 2014 

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References

1. Levy, D, Garrison, RJ, Savage, DD, Kannel, WB, Castelli, WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Eng J Med 1990; 322: 1561–1566.Google Scholar
2. Balakumar, P, Singh, AP, Singh, M. Rodent models of heart failure. J Pharmacol Toxicol Methods 2007; 56: 1–10.Google Scholar
3. Finck, BN, Kelly, DP. Peroxisome proliferator-activated receptor alpha (PPAR alpha) signaling in the gene regulatory control of energy metabolism in the normal and diseased heart. J Mol Cell Cardiol 2002; 34: 1249–1257.Google Scholar
4. Deschamps, AM, Spinale, FG. Pathways of matrix metalloproteinase induction in heart failure: bioactive molecules and transcriptional regulation. Cardiovasc Res 2006; 69: 666–676.Google Scholar
5. Balakumar, P, Rose, M, Singh, M. PPAR ligands: are they potential agents for cardiovascular disorders? Pharmacology 2007; 80: 1–10.Google Scholar
6. Van der Lee, KA, Vork, MM, De Vries, JE, et al. Long-chain fatty acid-induced changes in gene expression in neonatal cardiac myocytes. J Lipid Res 2000; 41: 41–47.CrossRefGoogle ScholarPubMed
7. Vosper, H, Khoudoli, GA, Graham, TL, Palmer, CN. Peroxisome proliferator-activated receptor agonists, hyperlipidaemia and atherosclerosis. Pharmacol Ther 2002; 95: 47–62.CrossRefGoogle ScholarPubMed
8. Erol, A. PPAR alpha activators may play role for the regression of ventricular hypertrophy in hypertensive and hyperlipidemic patients. Med Hypotheses 2006; 66: 1044–1045.Google Scholar
9. Singh, R, Singh, AP, Singh, M, Krishan, P. Impact of obesity on hypertension-induced cardiac remodeling: role of oxidative stress and its modulation by gemfibrozil treatment in rats. Free Radic Biol Med 2011; 50: 363–370.CrossRefGoogle ScholarPubMed
10. Singh, R, Krishan, P. Modulation of impact of high fat diet in pathological and physiological left ventricular cardiac hypertrophy by fluvastatin. Biomed Pharmacother 2010; 64: 147–153.Google Scholar
11. Lowry, OH, Rosebrough, NJ, Farr, AL, Randall, RJ. Protein measurement with folin–phenol reagent. J Biol Chem 1951; 193: 265–275.Google Scholar
12. Bishop, SP, Altschuld, RA. Increased glycolytic metabolism in cardiac hypertrophy and congestive failure. Am J Physiol 1970; 218: 153–159.Google Scholar
13. Kanda, H, Nohara, R, Hasegawa, K, Kishimoto, C, Sasayama, S. A nuclear complex containing PPARα/RXRα is markedly down regulated in the hypertrophied rat left ventricular myocardium with normal systolic function. Heart Vessels 2000; 15: 191–196.Google Scholar
14. Ichihara, S, Obata, K, Yamada, Y, et al. Attenuation of cardiac dysfunction by a PPAR-alpha agonist is associated with down regulation of redox-regulated transcription factors. J Mol Cell Cardiol 2006; 41: 318–329.Google Scholar
15. Collier, TJ, Coleman, PD. Divergence of biological and chronological aging: evidence from rodent studies. Neurobiol Aging 1991; 12: 685–693.Google Scholar
16. Porter, KE, Turner, NA. Cardiac fibroblasts: at the heart of myocardial remodeling. Pharmacol Ther 2009; 123: 255–278.Google Scholar
17. Zhao, W, Zhao, T, Chen, Y, Ahokas, RA, Sun, Y. Oxidative stress mediates cardiac fibrosis by enhancing transforming growth factor-beta1 in hypertensive rats. Mol Cell Biochem 2008; 317: 43–50.Google Scholar