Hong Kong Journal of Nephrology
Volume 11, Issue 2 , Pages 59-65, October 2009

Cardiac Damage Induced by Renal Ischemia/Reperfusion Injury in Hyperlipidemic Rats: Role of PPAR-α Agonist

  • Yagnik Bhalodia

      Affiliations

    • Department of Pharmacology, Smt. R.B. Patel Mahila Pharmacy College, Shreemati Nathibai Damodar Thackersey Women's University, Dist. Rajkot, Gujarat, India
    • Corresponding Author InformationCorrespondence to: Dr. Yagnik Bhalodia, Department of Pharmacology, Smt. R.B. Patel Mahila Pharmacy College, Bhavanagar Road, Kailash Nagar, Atkot-360040, Dist. Rajkot, Gujarat, India. Fax: (+ 91) 2821-288350
  • ,
  • Navin Sheth

      Affiliations

    • Department of Pharmaceutical Sciences, Saurashtra University, Dist. Rajkot, Gujarat, India
  • ,
  • Jitendra Vaghasiya

      Affiliations

    • Department of Pharmacology, Smt. R.B. Patel Mahila Pharmacy College, Shreemati Nathibai Damodar Thackersey Women's University, Dist. Rajkot, Gujarat, India
  • ,
  • Nurudin Jivani

      Affiliations

    • Department of Pharmacology, Smt. R.B. Patel Mahila Pharmacy College, Shreemati Nathibai Damodar Thackersey Women's University, Dist. Rajkot, Gujarat, India

Article Outline

Background

In view of the reported efficacy of peroxisome proliferator-activated receptor-α in renal ischemia/reperfusion (I/R) injury, the present study was designed to investigate the effect of fenofibrate on cardiac damage induced by renal I/R in hyperlipidemic rats.

Methods

Male Wistar rats were divided into five groups: Group 1, normal control; Group 2, hyperlipidemic control; Group 3, renal I/R injury; Group 4, hyperlipidemic + renal I/R injury; and Group 5, hyperlipidemic +renal I/R injury + fenofibrate. Hyperlipidemia was induced by feeding the rats with cholesterol (500 mg/kg per oral) in hydrogenated ground nut oil (as a vehicle) for 4 weeks. At the end of the fourth week, renal I/R injury was induced by occlusion of both renal vascular pedicles for 60 minutes, followed by 24-hour reperfusion. In the treatment group, fenofibrate (100 mg/kg per oral, dissolved in water containing 0.2% methyl cellulose) was given 2 weeks before I/R injury. At the end of the experiment, blood and heart were isolated for biochemical analysis.

Results

Hyperlipidemic I/R rats have significantly higher levels of cardiac lipid peroxidation, xanthine oxidase, nitric oxide and myeloperoxidase, and lower levels of antioxidant enzymes (reduced glutathione, superoxide dismutase and catalase) compared to non-hyperlipidemic I/R rats, the levels of which were restored after treatment with fenofibrate. Cardiac functional enzymes were normalized after the administration of fenofibrate.

Conclusion

This study elucidated the oxidative role of cardiac damage induced by renal I/R via inflammatory mediators, which was attenuated by fenofibrate.

Key words:  cardiac damage , fenofibrate , ischemia/reperfusion , kidney , oxidative stress

No full text is available. To read the body of this article, please view the PDF online.

 

Back to Article Outline

References 

  1. Campbell JD . Lifestyle, minerals and health . Med Hypotheses . 2001;57:521–531
  2. Snively CS , Gutierrez C . Chronic kidney disease: prevention and treatment of common complications . Am Fam Physician . 2004;70:1921–1928
  3. Kumai T , Oonuma S , Kitaoka Y , Tadokoro M , Kobayashi S . Biochemical and morphological characterization of spontaneously hypertensive hyperlipidaemic rats . Clin Exp Pharmacol Physiol . 2003;30:537–544
  4. Madore F . Vascular risk factors and renal failure . Med Sci . 2004;20:1100–1103
  5. Campos SB , Ori M , Dórea EL , Seguro AC . Protective effect of L-arginine on hypercholesterolemia-enhanced renal ischemic injury . Atherosclerosis . 1999;143:327–334
  6. Kelly KJ . Distant effects of experimental renal ischemia/reperfusion injury . J Am Soc Nephrol . 2003;14:1549–1558
  7. Erdogan H , Fadillioglu E , Yagmurca M , Ucar M , Irmak MK . Protein oxidation and lipid peroxidation after renal ischemiareperfusion injury: protective effects of erdosteine and N-acetylcysteine . Urol Res . 2006;34:41–46
  8. Serteser M , Koken T , Kahraman A , Yilmaz K , Akbulut G , Dilek ON . Changes in hepatic TNF-α levels, antioxidant status, and oxidation product after renal ischemia/reperfusion injury in mice . J Sur Res . 2002;107:234–240
  9. Finck BN , Kelly DP . Peroxisome proliferator-activated receptor-α (PPAR-α) signaling in the gene regulatory control of energy metabolism in the normal and diseased heart . J Mol Cell Cardiol . 2002;34:1249–1257
  10. Patel NS , di Paola R , Mazzon E , Britti D , Thiemermann C , Cuzzocrea S . Peroxisome proliferator-activated receptor-alpha contributes to the resolution of inflammation after renal ischemia/reperfusion injury . J Pharmacol Exp Ther . 2009;328:635–643
  11. Ahila S , Chatterjee P , Hattori Y , Brown P , Stewart K , Todorovic Z , et al.   Agonists of peroxisome-proliferator activated receptor- alpha (clofibrate and WY14643) reduce renal ischemia/reperfusion injury in the rat . Med Sci Monit . 2002;8:532–539
  12. Kumari CS , Govindasamy S , Sukumar E . Lipid lowering activity of Eclipta prostrate in experimental hyperlipidemia . J Ethnopharmacol . 2006;105:332–335
  13. Kontogiannis J , Burns KD . Role of AT1 angiotensin II receptors in renal ischemic injury . Am J Physiol . 1998;274(1 Pt 2):F79–F90
  14. Slater TF , Sawyer BC . The stimulatory effects of carbon tetrachloride and other halogenoalkanes or peroxidative reactions in liver fractions in vitro . Biochem J . 1971;123:805–814
  15. Levine RL , Garland D , Oliver CN , Amici A , Climent I , Lenz AG , et al.   Determination of carbonyl content in oxidatively modified proteins . In:  Packer L ,  Glazer AN editor. Methods in Enzymology, Oxygen Radicals in Biological Systems . 186: California: Academic Press; 1990;p. 464–478
  16. Moran MS , Depierre JW , Mannervik B . Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver . Biochim Biophys Acta . 1979;582:67
  17. Misra HP , Fridovich I . The role of superoxide anion in the auto- oxidation of epinephrine and a simple assay of SOD . J Biol Chem . 1972;247:3170
  18. Aebi H . Oxidoreductases acting on groups other than CHOH: catalase . In:  Colowick SP ,  Kaplan NO ,  Packer L editor. Methods in Enzymology . 105: London: Academic Press; 1984;p. 121–125
  19. Varley H . Practical Clinical Biochemistry . New Delhi: CBS Publishers; 1988;
  20. Prajda N , Weber G . Malignant transformation-linked imbalance: decreased xanthine oxidase activity in hepatomas . FEBS Lett . 1975;59:245–249
  21. Guevara I , Iwanejko J , Dembinska-Kiec A . Determination of nitrite/nitrate in human biological material by the simple Griess reaction . Clin Chim Acta . 1998;274:177–188
  22. Wei H , Frenkel K . Relationship of oxidative events and DNA oxidation in SENCAR mice to in vivo promoting activity of phorbol ester-type tumor promoters . Carcinogenesis . 1993;14:1195–1201
  23. Huang E , Kuo W , Chen Y , Chen T , Chang M , Lu M , et al.   Homocysteine and other biochemical parameters in type 2 diabetes mellitus with different diabetic duration or diabetic retinopathy . Clin Chim Acta . 2006;366:293–298
  24. Hagar HH . Folic acid and vitamin B12 supplementation attenuates isoprenaline-induced myocardial infarction in experimental hyperhomocysteinemic rats . Pharmacol Res . 2002;46:213–219
  25. Matsuyama M , Yoshimura R , Hase T , Kawahito Y , Sano H , Nakatani T . Study of cyclooxygenase-2 in renal ischemia-reperfusion injury . Transplant Proc . 2005;37:370–372
  26. Arnhold J , Osipov AN , Spalteholz H , Panasenko OM , Schiller J . Effects of hypochlorous acid on unsaturated phosphatidylcholines . Free Radic Biol Med . 2001;31:1111–1119
  27. Yagmurca M , Erdogan H , Iraz M , Songur A , Ucar M , Fadillioglu E . Caffeic acid phenethyl ester as a protective agent against doxorubicin nephrotoxicity in rats . Clin Chim Acta . 2004;348:27–34
  28. Ma XL , Lopez BL , Liu GL , Christopher TA , Gao F , Guo Y , et al.   Hypercholesterolemia impairs a detoxification mechanism against peroxynitrite and renders the vascular tissue more susceptible to oxidative injury . Circ Res . 1997;80:894–901
  29. Onody A , Csonka C , Giricz Z , Ferdinandy P . Hyperlipidemia induced by a cholesterol-rich diet leads to enhanced peroxynitrite formation in rat hearts . Cardiovasc Res . 2003;58:663–670
  30. Dominique D , Gele P , Petrault O , Six I , Furman C , Bouly M , et al.   Peroxisome proliferator activated receptor-α activation as a mechanism of preventive neuroprotection induced by chronic fenofibrate treatment . J Neurosci . 2003;23:6264–6271
  31. Chen XR , Besson VC , Palmier B , Garcia Y , Plotkine M , Leroux CM . Neurological recovery-promoting, anti-inflammatory, and anti-oxidative effects afforded by fenofibrate, a PPAR alpha agonist, in traumatic brain injury . J Neurotrauma . 2007;24:1119–1131
  32. Kładna A , Aboul-Enein HY , Kruk I , Lichszteld K , Michalska T . Scavenging of reactive oxygen species by some nonsteroidal anti- inflammatory drugs and fenofibrate . Biopolymers . 2006;82:99–105
  33. Wu J , Lin J , He Z , Ou B , Guo H . Effect of hyperlipidemia on endothelial VCAM-1 expression and the protective role of fenofibrate . Front Med China . 2007;1:356–358

PII: S1561-5413(09)60244-1

doi:10.1016/S1561-5413(09)60244-1

Hong Kong Journal of Nephrology
Volume 11, Issue 2 , Pages 59-65, October 2009