Advertisement

Molecular and Cellular Biochemistry

, Volume 273, Issue 1–2, pp 169–175 | Cite as

Ischemia-reperfusion leads to depletion of glutathione content and augmentation of malondialdehyde production in the rat heart from overproduction of oxidants: Can caffeic acid phenethyl ester (CAPE) protect the heart?

  • Mehmet Kaya OzerEmail author
  • Hakan Parlakpinar
  • Yilmaz Cigremis
  • Muharrem Ucar
  • Nigar Vardi
  • Ahmet Acet
Article

Abstract

During restoration of blood flow of the ischemic heart induced by coronary occlusion, free radicals cause lipid peroxidation with myocardial injury. Lipid peroxidation end-products, such as malondialdehyde (MDA), have been used to assess oxygen free radical-mediated injury of the ischemic-reperfused (I/R) myocardium in rats. This experimental study assessed the preventive effect of caffeic acid phenthyl ester (CAPE), antioxidant, on I/R-induced lipid peroxidation in the rat heart. We are also interested in the role of CAPE on glutathione (GSH) levels, an antioxidant whose levels are influenced by oxidative stress. I/R leads to the depletion of GSH which is the major intracellular nonprotein sulphydryl and plays an important role in the maintenance of cellular proteins and lipid in their functional state and acts primarily to protect these important structures against the threat of oxidation. In addition, we also examined morphologic changes in the heart by using light microscopy. The left coronary artery was occluded for 30 min and then reperfused for 120 min more before the experiment was terminated. CAPE (50 μM kg−1) was administered 10 min prior to ischemia and during occlusion by infusion. At the end of the reperfusion period, rats were sacrificed, and the heart was quickly removed for biochemical determination and histopathological analysis. I/R was accompanied by a significant increase in MDA production and decrease in GSH content in the rat heart. Administration of CAPE reduced MDA production and prevented depletion of GSH content. These beneficial changes in these biochemical parameters were also associated with parallel changes in histopathological appearance. These findings imply that I/R plays a causal role in heart injury due to overproduction of oxygen radicals or insufficient antioxidant and CAPE exert cardioprotective effects probably by the radical scavenging and antioxidant activities.

Keywords

caffeic acid phenethyl ester (CAPE) ischemia-reperfusion malondialdehyde (MDA) glutathione (GSH) heart rat 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Brown JM, Terada LS, Grosso MA, Whitmann GJ, Velasco SE, Patt A, Harken AH, Repine JE: Xanthine oxidase produces hydrogen peroxide which contributes to reperfusion injury of ischemic, isolated, perfused rat hearts. J Clin Invest 81: 1297–1301, 1988PubMedGoogle Scholar
  2. 2.
    Ambrosio G, Zweier JL, Flaherty JT: The relationship between oxygen radical generation and impairment of myocardial energy metabolism following post-ischemic reperfusion. J Mol Cell Cardiol 23: 1359–1374, 1991CrossRefPubMedGoogle Scholar
  3. 3.
    Park Y, Kenekal S, Kehrer JP: Oxidative changes in hypoxic rat heart tissue. Am J Physiol 260: 1395–1405, 1992Google Scholar
  4. 4.
    Burton KP, McCord JM, Ghai G: Myocardial alterations due to free-radical generation. Am J Physiol 246: 776–783, 1984Google Scholar
  5. 5.
    Ferrari R, Ceconi C, Currelo S, Cargoni A, Agnoletti G, Boffa GM, Visioli O: Intracellular effects of myocardial ischemia and reperfusion: role of calcium and oxygen. Eur Heart J 7: 3–12, 1986Google Scholar
  6. 6.
    Meister A, Anderson MF: Glutathione. Ann Rev Biochem 52: 711–760, 1993CrossRefGoogle Scholar
  7. 7.
    Sies H, Graf P: Hepatic thiol and glutathione efflux under the influence of vasopressin, phenylephrine and adrenaline. Biochem J 226: 545–549, 1985PubMedGoogle Scholar
  8. 8.
    Lu SC, Garcia-Ruiz C, Kuhlenkamp J, Ookhtens M, Salas-Prato M, Kaplowitz N: Hormonal regulation of glutathione efflux. J Biol Chem 265: 16088–16095, 1990PubMedGoogle Scholar
  9. 9.
    Liu JH, Sato C, Takano T, Marumo F: Characterization of vasopressin-mediated GSH efflux from Hep G2 cells, significance of protein kinase C. Life Sci 52: 1217–1223, 1993CrossRefPubMedGoogle Scholar
  10. 10.
    Leichtweis S, Ji LL: Glutathione deficiency intensifies ischemia-reperfusion induced cardiac dysfunction and oxidative stress. Acta Physiol Scand 172: 1–10, 2001CrossRefPubMedGoogle Scholar
  11. 11.
    Blaustein A, Deneke SM, Stolz RI, Baxter D, Healey N, Fanburg BL: Myocardial glutathione depletion impairs recovery after short periods of ischemia. Circulation 80: 1449–1457, 1989PubMedGoogle Scholar
  12. 12.
    Werns SW, Fantone JC, Ventura A, Lucchesi BR: Myocardial glutathione depletion impairs recovery of isolated blood-perfused hearts after global ischemia. J Mol Cell Cardiol 24: 1215–1220, 1992CrossRefPubMedGoogle Scholar
  13. 13.
    Sahna E, Acet A, Ozer MK, Olmez E: Myocardial ischemia-reperfusion in rats: reduction of infarct size by either supplemental physiological or pharmacological doses of melatonin. J Pineal Res 33(4): 234–238, 2002CrossRefPubMedGoogle Scholar
  14. 14.
    Ozer MK, Parlakpinar H, Acet A: Reduction of ischemia-reperfusion induced myocardial infarct size in rats by caffeic acid phenethyl ester (CAPE). Clin Biochem 37(8): 702–705, 2004CrossRefPubMedGoogle Scholar
  15. 15.
    Irmak MK, Koltuksuz U, Kutlu NO, Yagmurca M, Ozyurt H, Karaman A, Akyol O: The effect of caffeic acid phenethyl ester on ischemia-reperfusion injury in comparison with alpha-tocopherol in rat kidneys. Urol Res 29(3): 190–193, 2001CrossRefPubMedGoogle Scholar
  16. 16.
    Ilhan A, Koltuksuz U, Ozen S, Uz E, Ciralik H, Akyol O: The effects of caffeic acid phenethyl ester (CAPE) on spinal cord ischemia/reperfusion injury in rabbits. Eur J Cardiothorac Surg 16(4): 458–463, 1999CrossRefPubMedGoogle Scholar
  17. 17.
    Koltuksuz U, Ozen S, Uz E, Aydinc M, Karaman A, Gultek A, Akyol O, Gursoy MH, Aydin E: caffeic acid phenethyl ester prevents intestinal reperfusion injury in rats. J Pediatr Surg 34(10): 1458–1462, 1999CrossRefPubMedGoogle Scholar
  18. 18.
    Koltuksuz U, Irmak MK, Karaman A, Uz E, Var A, Ozyurt H, Akyol O: Testicular nitric oxide levels after unilateral testicular torsion/detorsion in rats pretreated with caffeic acid phenethyl ester. Urol Res 28(6): 360–363, 2000CrossRefPubMedGoogle Scholar
  19. 19.
    Vermeulen NPE, Baldew GS: The role of lipid peroxidation in the nephrotoxicity of cisplatin. Biochem Pharmacol 44: 1193–119, 1992CrossRefPubMedGoogle Scholar
  20. 20.
    Gupta A, Gupta A, Nigam D, Shukla GS, Agarwal AK: Profile of reactive oxygen species generation and antioxidative mechanisms in the maturing rat kidney. J Appl Toxicol 19: 55–59, 1999CrossRefPubMedGoogle Scholar
  21. 21.
    Kirshenbaum LA, Singal PK: Increase in endogenous antioxidant enzymes protects hearts against reperfusion injury. Am J Physiol 265: 484–493, 1993Google Scholar
  22. 22.
    Werns SW, Fantone JC, Ventura A, Lucchesi BR: Myocardial glutathione depletion impairs recovery of isolated blood-perfused hearts after global ischemia. J Mol Cell Cardiol 24: 1215–1220, 1992CrossRefPubMedGoogle Scholar
  23. 23.
    Ji LL, Fu RG, Mitchell EW, Griffiths M, Waldrop TG, Swartz HM: Cardiac hypertrophy alters myocardial response to ischemia and reperfusion in vivo. Acta Physiol Scand 151: 279–290, 1994PubMedGoogle Scholar
  24. 24.
    Ji LL, Fu RG, Waldrop TG, Liu KJ, Swartz HM: Myocardial response to regional ischemia and reperfusion in vivo in rat heart. Can J Physiol Pharmacol 71: 811–817, 1993PubMedGoogle Scholar
  25. 25.
    Sies H, Graf P: Hepatic thiol and glutathione efflux under the influence of vasopressin, phenylephrine and adrenaline. Biochem J 226: 545–549, 1985PubMedGoogle Scholar
  26. 26.
    Kloner RA, Przyklenk K, Wgittaker P: Deletorious effects of oxygen radicals in ischemia/reperfusion: resolved and unresolved issues. Circulation 80: 1115–1127, 1989PubMedGoogle Scholar
  27. 27.
    Kukreja RC, Hess ML: The oxygen free radical system: From equations through membrane-protein interactions to cardiovascular injury and protection. Cardiovasc Res 26: 641–665, 1992PubMedGoogle Scholar
  28. 28.
    Hepsen IF, Er H, Cekic O: Topically applied water extract of propolis to suppress corneal neurovascularisation in rabbits. Ophthalmic Res 31: 426, 1999CrossRefPubMedGoogle Scholar
  29. 29.
    Sud’ina GF, Mirzoeva OK, Puskareva MA, et~al: Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxdant properties. FEBS Lett 329: 21, 1993CrossRefPubMedGoogle Scholar
  30. 30.
    Russo A, Longo R, Vanella A: Antioxidant activity or propolis: role of caffeic acid phenethyl ester and galangin. Fitoterapia 73: 21–29, 2002CrossRefGoogle Scholar
  31. 31.
    Leichtweis S, Leeuwenburgh C, Bejma J, Ji LL: Aged rat hearts are not more susceptible to ischemia-reperfusion injury in vivo: role of glutathione. Mech Ageing Dev 15: 503–518, 2001CrossRefGoogle Scholar
  32. 32.
    Park JL, Lucchesi BR: Mechanisms of myocardial reperfusion injury. Ann Thorac Surg 68: 1905–1912, 1999CrossRefPubMedGoogle Scholar
  33. 33.
    Mirzoeva OK, Sud’ina GF, Pushkareva MA, Korshunova GA, Sumbatian NV, Varfolomeev SD: Lipophilic derivatives of caffeic acid as lipoxygenase inhibitors with antioxidant properties. Bioorg Khim 21(2): 143–151, 1995PubMedGoogle Scholar
  34. 34.
    Ferrari R, Guardigli G, Mele D, Percoco GF, Ceconi C, Curello S: Oxidative stress during myocardial ischemia and heart failure. Curr Pharm Des 10(14): 1699–711, 2004CrossRefPubMedGoogle Scholar
  35. 35.
    Jolly SR, Kane WJ, Bailie MB, Abrams GD, Lucchesi BR: Canine myocardial reperfusion injury: its reduction by the combined administration of superoxide dismutase and catalase. Circ Res 54: 277–285, 1994Google Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Mehmet Kaya Ozer
    • 1
    • 5
    Email author
  • Hakan Parlakpinar
    • 2
  • Yilmaz Cigremis
    • 3
  • Muharrem Ucar
    • 4
  • Nigar Vardi
    • 4
  • Ahmet Acet
    • 2
  1. 1.Department of Pharmacology, Faculty of MedicineSuleyman Demirel UniversityIspartaTurkey
  2. 2.Department of Pharmacology, Faculty of MedicineInonu UniversityMalatyaTurkey
  3. 3.Department of Biology, Faculty of Art and ScienceKafkas UniversityKarsTurkey
  4. 4.Department of Histology, Faculty of MedicineInonu UniversityMalatyaTurkey
  5. 5.Department of Pharmacology, Faculty of MedicineSuleyman Demirel UniversityIspartaTurkey

Personalised recommendations