Skip to main content
SpringerLink
Log in

The beneficial effect of 2′-deoxycoformycin in renal ischemia-reperfusion is mediated both by preservation of tissue ATP and inhibition of lipid peroxidation

  • Original
  • Published:
International Journal of Clinical and Laboratory Research

Abstract

Renal ischemia injures the renal tubular cell by disrupting the vital cellular metabolic machinery. Further cell damage is caused when the blood flow is restored by oxygen free radicals that are generated from xanthine oxidase. Oxygen radicals cause lipid peroxidation of cell and organelle membranes, disrupting the structural integrity and capacity for cell transport and energy metabolism. In the present study, the possible therapeutic usefulness of the adenosine deaminase inhibitor, 2′-deoxycoformycin (DCF), during renal ischemia and reperfusion injury was investigated. The effects of DCF on renal malondialdehyde (MDA) and ATP levels were studied after 45 min ischemia and 15 min subsequent reperfusion in rat kidneys. MDA levels remained unchanged during ischemia, but increased after the subsequent reperfusion. DCF pretreatment (2.0 mg/kg i.m.) decreased MDA and increased ATP levels during the ischemia-reperfusion period. DCF exerts a dual protective action by facilitating purine salvage for ATP synthesis and inhibiting oxygen radical-induced lipid peroxidation. These results suggest that DCF therapy could be beneficial in the treatment of ischemia-reperfusion renal injuries.

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. Paller MS. Acute renal failure: controversies, clinical trials, and future. Semin Nephrol 1998; 18:482.

    PubMed  CAS  Google Scholar 

  2. Hems DA, BrosnaN JT. Effects of ischaemia on content of metabolites in rat liver and kidney in vivo. Biochem J 1970; 120:105.

    PubMed  CAS  Google Scholar 

  3. Paller MS, Hoidal JR, Ferris TF. Oxygen free radicals in ischemic acute renal failure in the rat. J Clin Invest 1984; 74:1156.

    Article  PubMed  CAS  Google Scholar 

  4. Greene EL, Paller MS. Xanthine oxidase produces O2-. in posthypoxic injury of renal epithelial cells. Am J Physiol 1992; 263:F251.

    Google Scholar 

  5. Linas SL, Whittenburg D, Repine JE. Role of xanthine oxidase in ischemia/reperfusion injury. Am J Physiol 1990; 258:F711.

    Google Scholar 

  6. Granger DN, Rutili G, McCord JM. Superoxide radicals in feline intestinal ischemia. Gastroenterology 1981; 81:22.

    PubMed  CAS  Google Scholar 

  7. Cross CE, Halliwell B, Borish ET, et al. Oxygen radicals and human disease (clinical conference). Ann Intern Med 1987; 107:526.

    PubMed  CAS  Google Scholar 

  8. Greene EL, Paller MS. Oxygen free radicals in acute renal failure. Miner Electrolyte Metab 1991; 17:124.

    PubMed  CAS  Google Scholar 

  9. Yavuz O, Turkozkan N, Bilgihan A, Dogulu F, Aykol S. The effect of 2-chloroadenosine on lipid peroxide level during experimental cerebral ischemia-reperfusion in gerbils. Free Radic Biol Med 1997; 22:337.

    Article  PubMed  CAS  Google Scholar 

  10. Turkozkan N, Bilighan A, Cayci B, Dogulu F, Aykol S. The effects of 2-chloroadenosine and deoxycoformycin on the ATP level, Na-K ATPase activity in experimental brain ischemia of gerbil. Neurol Res 1996; 18:345.

    PubMed  CAS  Google Scholar 

  11. Turkozkan N, Aykol S, Bilgihan A, Yavuz O, Cayci B, Dogulu F. The effect of 2-chloroadenosine on the ATP level Na,K ATPase activity in experimental brain ischemia of gerbil. Gen Pharmacol 1996; 27:165.

    Article  PubMed  CAS  Google Scholar 

  12. Phillips E, Newsholme EA. Maximum activities, properties and distribution of 5′ nucleotidase, adenosine kinase and adenosine deaminase in rat and human brain. J Neurochem 1979; 33:553.

    Article  PubMed  CAS  Google Scholar 

  13. Aricioglu A, Aydin S, Turkozkan N, Durmus O. The effect of allopurinol on Na+K+ATPase related lipid peroxidation in ischemic and reperfused rabbit kidney. Gen Pharmacol 1994; 25:341.

    Article  PubMed  CAS  Google Scholar 

  14. Mihara M, Uchiyama M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 1978; 86:271.

    Article  PubMed  CAS  Google Scholar 

  15. Lamprecht WI, Trautsch E. Adenosine 5-triphosphate determination with hexokinase and glucose-6-P-dehydrogenase. In: Bergmeyer HU, ed. Methods of enzymatic analysis. London: Academic Press; 1971:543–551.

    Google Scholar 

  16. Goldberg DM. Serum adenosine deaminase in differential diagnosis of jaundice. Br Med J 1965; 1:353.

    Article  PubMed  CAS  Google Scholar 

  17. Paller MS, Hebbel RP. Ethane production as a measure of lipid peroxidation after renal ischemia. Am J Physiol 1986; 251:F839.

    Google Scholar 

  18. Pfaller W. Structure function correlation on rat kidney. Quantitative correlation of structure and function in the normal and injured rat kidney. Adv Anat Embryol Cell Biol 1982; 70:1.

    PubMed  CAS  Google Scholar 

  19. Karasawa A, Kubo K. Protection by benidipine hydrochloride (KW-3049), a calcium antagonist, of ischemic kidney in rats via inhibitions of Ca-overload, ATP-decline and lipid peroxidation. Jpn J Pharmacol 1990; 52:553.

    Article  PubMed  CAS  Google Scholar 

  20. Green CJ, Healing G, Lunec J, Fuller BJ, Simpkin S. Evidence of free-radical-induced damage in rabbit kidneys after simple hypothermic preservation and autotransplantation. Transplantation 1986; 41:161.

    Article  PubMed  CAS  Google Scholar 

  21. Agarwal RP, Spector T, Parks RE Jr. Tight-binding inhibitors. IV. Inhibition of adenosine deaminases by various inhibitors. Biochem Pharmacol 1977; 26:359.

    Article  PubMed  CAS  Google Scholar 

  22. Nosaka K, Takahashi T, Nishi T, et al. An adenosine deaminase inhibitor prevents puromycin aminonucleoside nephrotoxicity. Free Radic Biol Med 1997; 22:597.

    Article  PubMed  CAS  Google Scholar 

  23. Stromski ME, Waarde A van, Avison MJ, et al. Metabolic and functional consequences of inhibiting adenosine deaminase during renal ischemia in rats. J Clin Invest 1988; 82:1694.

    Article  PubMed  CAS  Google Scholar 

  24. Bolling SF, Bies LE, Bove EL, Gallagher KP. Augmenting intracellular adenosine improves myocardial recovery. J Thorac Cardiovasc Surg 1990; 99:469.

    PubMed  CAS  Google Scholar 

  25. Sandhu GS, Burrier AC, Janero DR. Adenosine deaminase inhibitors attenuate ischemic injury and preserve energy balance in isolated guinea pig heart. Am J Physiol 1993; 265:H1249.

    Google Scholar 

  26. Lin Y, Phillis JW. Deoxycoformycin and oxypurinol: protection against focal ischemic brain injury in the rat. Brain Res 1992; 571:272.

    Article  PubMed  CAS  Google Scholar 

  27. Jordan JE, Zhao ZQ, Sato H, Taft S, Vinten Johansen J. Adenosine A2 receptor activation attenuates reperfusion injury by inhibiting neutrophil accumulation, superoxide generation and coronary endothelial adherence. J Pharmacol Exp Ther 1997; 280:301.

    PubMed  CAS  Google Scholar 

  28. Wu PH, Phillis JW, Thierry DL. Adenosine receptor agonists inhibit K+-evoked Ca2+ uptake by rat brain cortical synaptosomes. J Neurochem 1982; 39:700.

    Article  PubMed  CAS  Google Scholar 

  29. Sumpio BE, Hull MJ, Baue AE, Chaudry IH. Comparison of effects of ATP-MgCl2 and adenosine-MgCl2 on renal function following ischemia. Am J Physiol 1987; 252:R388.

    Google Scholar 

  30. Phillis JW, O’Regan MH. Deoxycoformycin antagonizes ischemia-induced neuronal degeneration. Brain Res Bull 1989; 22:537.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Biochemistry, Gazi University School of Medicine, Ankara, Turkey

    M. Vakur Bor, A. Bilgihan, C. Çevik & N. Türközkan

  2. Department of Surgery, Gazi University School of Medicine, Ankara, Turkey

    O. Durmuş

Authors
  1. M. Vakur Bor
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. O. Durmuş
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Bilgihan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Çevik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N. Türközkan
    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

Bor, M.V., Durmuş, O., Bilgihan, A. et al. The beneficial effect of 2′-deoxycoformycin in renal ischemia-reperfusion is mediated both by preservation of tissue ATP and inhibition of lipid peroxidation. Int J Clin Lab Res 29, 75–79 (1999). https://doi.org/10.1007/s005990050067

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s005990050067

Key words

Search

Navigation