Skip to main content
SpringerLink
Log in

Effects of deferoxamine on H2O2-induced oxidative stress in isolated rat heart

  • Original Contribution
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Abstract

During myocardial reperfusion injury, iron has been implicated in the Fenton based generation of hydroxyl radical, ·OH, leading to further organ injury. Although previous studies have investigated the protective effect of iron chelators including deferoxamine (DFX) in myocardial reperfusion injury, there is little information regarding the role of iron chelation during oxidative stress produced by H2O2 on the heart. Isolated hearts from male Sprague-Dawley rats were retrograde-perfused with Krebs-Henseleit solution at 5 ml/min. After a 60-min equilibration, oxyradical challenge was instituted by the addition of H2O2 (200–600 μM) to the perfusate for 60 min. A subgroup of animals received DFX (400 μM) in the perfusate prior to challenge with 400 μM H2O2. Contractility was continuously monitored; perfusate samples for glutathione (GSH) and lactate dehydrogenase (LDH) estimations were collected at 30-min intervals. Headspace ethane, an indicator of lipid peroxidation, was estimated at 30-min intervals by gas chromatography. Control hearts maintained contractility during the perfusion period. H2O2 perfusion caused a dose dependent decrease in myocardial contractility; DFX pretreatment was partialy protective. Headspace ethane slowly accumulated in control hearts; perfusion with H2O2 caused dose dependent increase in ethane accumulation indicative of enhanced lipid peroxidation. GSH and LDH in the perfusate remained low in control hearts. In contrast, H2O2 treated hearts had a dose dependent inclease in the efflux of GSH and LDH which was markedly increased by perfusion with 600 μM H2O2. Pretreatment with DFX did not significantly reduce GSH or LDH efflux from hearts perfused with peroxide. While H2O2 perfused with peroxide. While H2O2 perfusion causes a dose dependent decrease in myocardial contractility with a corresponding increase in headspace ethane release with GSH & LDH efflux indicative of oxidative stress, concurrent treatment with DFX reduces myocardial dysfunction and ethane generation. However, sublethal damage of plasma membrane still continues as reflected by continuous enhancement of LDH efflux, possibly indicating involvement of other reactive species besides hydroxyl radical.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Anderson GF, Dutta S (1991) Electromechanical effects of menadione on isolated rat heart in relation to oxidative stress. Free Radical Biol Med 11:169–177

    Google Scholar 

  2. Balla G, Jacob HS, Eaton JW, Belcher JD, Vercellotti GM (1991) Hemin: A possible physiological mediator of low density lipoprotein oxidation and endothelial cell injury. Arterioscler Thromb 11:1700–1711

    Google Scholar 

  3. Buettner GR (1993) The pecking order of free radicals and antioxidants: Lipid peroxidation, α-tocopherol, and ascorbate. Arch Biochem Biophys 300:535–543

    Google Scholar 

  4. DeBoer DA, Clark RE (1992) Iron chelation in myocardial preservation after ischemia-reperfusion injury: The importance of pretreatment and toxicity. Ann Thorac Surg 53:412–418

    Google Scholar 

  5. Dutta S, Müller A, Ishikawa T, Zimmer Z, Sies H (1988) Alkane production by isolated heart and lung. Toxicol Lett 44:55–64

    Google Scholar 

  6. Ely D, Dunphy G, Dollwet H, Richter H, Sellke F, Azodi M (1992) Maintenance of left ventricular function (90%) after twenty-four-hour preservation with deferoxamine. Free Radical Biol Med 12:479–485

    Google Scholar 

  7. Farber JL (1994) Mechanisms of cell injury by activated oxygen species. Environ Hlth Perspect 102 (Suppl 10):17–24

    Google Scholar 

  8. Fenton HJH (1894) Oxidation of tartaric acid in presence of iron. J Chem Soc 65:899–910

    Google Scholar 

  9. Frei B (Ed) (1994) Natural Antioxidants in Health and Disease Academic Press, Orlando, Fl.

    Google Scholar 

  10. Halliwell B, Gutteridge JMC (1984) Oxygen toxicity, oxygen radicals, transition metals, and disease. Biochem J 219:1–14

    Google Scholar 

  11. Haber F, Weiss J (1934) The catalytic decomposition of hydrogen peroxide by iron salts. Proc R Soc A 147:332–351

    Google Scholar 

  12. Halliwell B, Gutteridge JMC (1986) Oxygen free radicals and iron in relation to biology and medicine: Some problems and concepts. Arch Biochem Biophys 246:501–514

    Google Scholar 

  13. Halliwell B, Gutteridge JMC (1990) Role of free radicals and catalytic metal ions in human disease: An overview. Meth Enzymol 186:1–85

    Google Scholar 

  14. Imlay JA, Chin SM, Linn S (1988) Toxic DNA damage by hydrogen peroxide through the Fenton reaction in vivo and in vitro. Science 240:640–642

    Google Scholar 

  15. Ishikawa T, Sies H (1984) Cardiac transport of glutathione disulfide and S-conjugate. Studies with isolated rat heart during hydroperoxide metabolism. J Biol Chem 259:3838–3843

    Google Scholar 

  16. Katoh S, Toyama J, Kodama I, Kamiya K, Akita T, Abe T (1993) Deferoxamine reduces the reperfusion injury in isolated neonatal rabbit hearts after hypothermic preservation. Jap J Surgery 23:424–429

    Google Scholar 

  17. Khan AU, Kasha M (1994) Singlet molecular oxygen in the Haber-Weiss reaction. Proc Natl Acad Sci. USA 91: 12365–12367

    Google Scholar 

  18. Koster JF, Slee RG (1986) Ferritin: a physiological iron donor for microsomal lipid peroxidation. FEBS Lett 199:85–88

    Google Scholar 

  19. Kimura M, Maeda K, Hayashi S (1992) Cytosolic calcium increase in coronary endothelial cells after H2O2 exposure and the inhibitory effect of U78517F. Br J Pharmacol 107:488–493

    Google Scholar 

  20. Lesnefsky EJ, Allen KGD, Canea FP, Horwitz LD (1992) Iron-catalyzed reactions cause lipid peroxidation in the intact heart. J Mol Cell Cardiol 24:1031–1038

    Google Scholar 

  21. Lesnefsky EJ, Repine JE, Horwitz LD (1990) Deferoxamine pretreatment reduces canine infarct size and oxidative injury. J Pharmacol Exp Therap 253:1103–1109

    Google Scholar 

  22. Mazur A, Baez S, Shorr E (1955) The mechanism of iron release from ferritin as related to its biological properties. J Biol Chem 213:147–160

    Google Scholar 

  23. McCord JM (1992) Iron, and Oxidative Balance. In: Iron and Human Diseases (Ed.) Lauffer RB), CRC Press, Book Raton, Fl, pp 509–518

    Google Scholar 

  24. McCord JM, Day ED (1978) Superoxide-dependent production of hydroxyl radical catalyzed by iron-EDTA complex. FEBS Lett 86:139–142

    Google Scholar 

  25. Menascha P, Antebi H, Alcindo I.-G, Teifer E, Perez G, Giudicelli Y, Nordman R, Piwnica A (1990) Iron chelation by deferoxamine inhibits lipid peroxidation during cardiopulmonary bypass in humans. Circulation 82 Suppl IV:390–396

    Google Scholar 

  26. Monteiro HP, Winterbourn CC (1988) The superoxide-dependent transfer of iron from ferritin to transferrin and lactoferrin. Biochem J 256:923–928

    Google Scholar 

  27. Morel I, Cillard J, Lescoat G, Sergent O, Pasdeloup N, Ocaktan AZ, Abdullah MA, Brissot P, Cillard P (1992) Antioxidant and free radical scavenging activities of the iron chelators pyoverdin and hydroxyprid-4-ones in iron-loaded hepatocyte cultures: comparison of their mechanism of protection with that of desferoxamine. Free Radical Biol Med 13:499–508

    Google Scholar 

  28. Reddan JR, Sevilla MD, Giblin FJ, Padgaonkar V, Dziedzic DC, Leverenz V, Misra IC, Peters LJ (1993) The superoxide dismutase mimic TEMPOL protects cultured rabbit lens epithelial cells from hydrogen peroxide insult. Exp Eye Res 56:543–554

    Google Scholar 

  29. Sempos CT, Looker AC, Gillum RF, Makuc DM (1994) Body iron stores and risk of coronary heart disease. New Eng J Med 330:1119–1124

    Google Scholar 

  30. Sies H (1986) Biochemistry of oxidative stress. Angew Chemie Int Ed Engl 25: 1058–1071

    Google Scholar 

  31. Takemura G, Onodera T, Millard RW, Ashraf M (1993) Demonstration of hydroxyl radical and its role in hydrogen peroxide-induced myocardial injury: Hydoxyl radical dependent and independent mechanisms. Free Radical Biol Med 15:13–25

    Google Scholar 

  32. Thies RL, Autor AP (1991) Reactive oxygen injury to cultured pulmonary artery endothelial cells: mediation by poly (ADP-ribose) polymerase activation causing NAD depletion and altered energy balance. Arch Biochem Biophys 286:353–363

    Google Scholar 

  33. Tietze F (1969) Enzymatic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem 27:502–522

    Google Scholar 

  34. van Jaarsveld H, Kuyl JM, Alberts DW (1992) The protective effect of desferal on rat myocardial mitochondria is not prolonged after withdrawal of desferal. Basic Res Cardiol 87:47–53

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Harper Hospital, 3990 John R, 48201, Detroit, Michigan, USA

    S. A. Dulchavsky, S. B. Davidson, W. J. Cullen, T. P. A. Devasagayam & L. N. Diebel

  2. Department of Surgery and Pharmacology, Wayne State University School of Medicine, 48201, Detroit, Michigan, USA

    S. Dutta

Authors
  1. S. A. Dulchavsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. B. Davidson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. J. Cullen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T. P. A. Devasagayam
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L. N. Diebel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. Dutta
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dulchavsky, S.A., Davidson, S.B., Cullen, W.J. et al. Effects of deferoxamine on H2O2-induced oxidative stress in isolated rat heart. Basic Res Cardiol 91, 418–424 (1996). https://doi.org/10.1007/BF00788722

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00788722

Key words

Search

Navigation