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Effects of N-(2-mercaptopropionyl)glycine on ischemic-reperfused dog kidney in vivo and membrane preparation in vitro

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Abstract

The results of our experiments demonstrated that one hour of ischemia followed by one hour of reflow in the kidney caused a reduction in (Na+K+)ATPase activity and microsomal sulfhydryl content as well as an increase in microsomal lipid peroxidation. Renal venous malondialdehyde concentration was increased soon after reperfusion of the ischemic kidney. All these changes were rectified by an infusion of 0.123 mmol N-(2-mercaptopropionyl)glycine/kg over a 70 min period. On the other hand, an in vitro addition of 0.01–0.5 mM N-(2-mercaptopropionyl)glycine to a membrane preparation in the presence of H202 and Fe3+ did not prevent but rather potentiated the free radical effect on the enzyme activity. However, addition of superoxide dismutase alone or with catalase together with 2-MPG were effective in preventing the enzyme depression induced by H202. The results therefore indicate that free radical generation participates in the evolution of ischemia/reperfusion cell injury and thiol-reducing agents may be beneficial in alleviating the cell damage in vivo.

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References

  1. Chance B, Sies H, Boveris A: Hydroperoxide metabolism in mammalian organs. Physiol Rev 59:527–605, 1979

    CAS  PubMed  Google Scholar 

  2. Freeman BA, Crapo JD: Biology of disease. Free radicals and tissue injury. Lab Invest 47:412–426, 1982

    CAS  PubMed  Google Scholar 

  3. Weiss SJ, LoBuglio AF: Phagocyte-generated oxygen metabolites and cellular injury. Lab Invest 47:5–18, 1982

    Google Scholar 

  4. McCord JM: Oxygen-derived free radicals in postischemic tissue injury. New Engl J Med 312:159–163, 1985

    Google Scholar 

  5. Werns SW, Shea MJ, Lucchesi BR: Free radicals in ischemic myocardial injury. J Free Rad Biol Med 1:103–110, 1985

    Google Scholar 

  6. Kako KJ: Membrane damage caused by lipid peroxidation in myocardial ischemia. Jikeikai Med J 32:609–639, 1985

    Google Scholar 

  7. Wolff SP, Garner A, Dean RT. Free radicals, lipids and protein degradation. TIBS 11:27–31, 1986

    Google Scholar 

  8. Kako KJ: Free radical effects on membrane protein in myocardial ischemia/reperfusion injury. J Mol Cell Cardiol 19:209–211, 1987

    Google Scholar 

  9. Venkatachalam MA, Bernard DB, Donohoe JF, Levinsky NG: Ischemic damage and repair in the rat proximal tubule. Differences among the Sl, S2 and S3 segments. Kidney Int 14:31–49, 1978

    Google Scholar 

  10. Brezis M, Rosen S, Silva P, Epstein FH: Renal ischemia. A new perspective. Kidney Int 26:375–383, 1984

    CAS  PubMed  Google Scholar 

  11. Mason J, Thiel G (eds) Workshop on the role of renal medullary circulation in the pathogenesis of acute renal failure. Nephron 31:289–323, 1982

    Google Scholar 

  12. Kako KJ, Kato M, Matsuoka T, Mustapha A: The depression of membrane-bound (Na+K+)ATPase activity induced by free radicals and by ischemia of the kidney. Am J Physiol in press

  13. Kako KJ, Kato M, Matsuoka T, Kaminishi T: Difference in in vitro effects of two oxidants, hydrogen peroxide and hypochlorite, on isolated membranes and cardiomyocytes. Abst J Mol Cell Cardiol 19, Suppl 4,S-78, 1987

    Google Scholar 

  14. Jorgensen PL: Sodium and potassium ion pump in kidney tubules. Physiol Rev 60:864–917, 1980

    Google Scholar 

  15. Williams R, Gasbarrini G, Davis M (eds). Recent advances in 2-MPG treatment of liver diseases. Edtrice Compositori Bologna 1–383, 1981

  16. Mitsos SE, Askew TE, Fantone JC, Kunkel SL, Abrams GD, Schork A, Lucchesi BR: Protective effects of N-2-mercaptopropionyl glycine against myocardial reperfusion injury af neutrophil depletion in the dog: evidence for the role of intracellular-derived free radicals. Circulation 73:1077–1086, 1986

    Google Scholar 

  17. Myers M, Bolli R, Lekich RF, Hartley CJ, Roberts R: N-2-mercaptopropionylglycine improves recovery of myocardial function after reversible regional ischemia. J Am Coll Cardiol 8:1161–1168, 1986

    Google Scholar 

  18. Jorgensen PL: Purification and characterization of (Na+K+)ATPase. III. Purification from the outer medulla of mammalian kidney after selective removal of membrane components by sodium dodecylsulphate. Biochim Biophys Acta 356:36–52, 1974

    Google Scholar 

  19. Kako KJ, Zaror-Behrens G, Peckett SD: Phosphatidic acid synthesis in the heart. Effect of age and species difference in the mitochondrial and microsomal synthesis. Can J Biochem 55:308–314, 1977

    Google Scholar 

  20. Kayawake S, Narbaitz R, Kako KJ: Effects of chloroquine and Nifedipine on the phospholipid content and enzyme activity in the subcellular fraction of ischemic rat liver. Basic Res Cardiol 77:140–157, 1982

    Google Scholar 

  21. Takahashi K, Kako KJ: The effect of a calcium channel antagonist, Nisoldipine, on the ischemia-induced change of canine sarcolemmal membrane. Basic Res Cardiol 78:326–337, 1983

    Google Scholar 

  22. Peterson CL: A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal Biochem 83:346–356, 1977

    CAS  PubMed  Google Scholar 

  23. Sakai H: Quantitative microdetermination of total -SH groups in proteins. Anal Biochem 26:269–276, 1968

    Google Scholar 

  24. Ohkawa H, Ohishi N, Yagi K: Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358, 1979

    CAS  PubMed  Google Scholar 

  25. Weber K, Osborne M: The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J Biol Chem 244:4406–4412, 1969

    Google Scholar 

  26. Balint P, Szocs E: Intrarenal hemodynamics following temporary occlusion of the renal artery in the dog. Kidney Int 10, S-128–136, 1976

    Google Scholar 

  27. Karlberg L, Norlen BJ, Ojteg G, Wolgast M: Impaired medullary circulation in postischemic acute renal failure. Acta Physiol Scand 118:11–17, 1983

    Google Scholar 

  28. Zimmer G, Beyersdorf F, Fuchs J: Decay of structure and function of heart mitochondria during hypoxia and related stress and its treatment. Mol Physiol 8:495–513, 1985

    Google Scholar 

  29. Starke PE, Farber JL: Endogenous defenses against the cytotoxicity of hydrogen peroxide in cultured rat hepatocytes. J Biol Chem 260:86–92, 1985

    Google Scholar 

  30. Reeves JP, Bailey CA, Hale CC: Redox modification of sodium-calcium exchange activity in cardiac sarcolemmal vesicles. J Biol Chem 261:4948–4988, 1986

    Google Scholar 

  31. Paller MS, Hebbel RP: Ethane production as a measure of lipid peroxidation after renal ischemia. Am J Physiol 251:F839–843, 1986

    Google Scholar 

  32. Paller MS, Hoidal JR, Ferris TF: Oxygen free radicals in ischemic acute renal failure in the rat. J Clin Invest 74:1156–1164, 1984

    Google Scholar 

  33. Garner A, Jamal Z, Slater TF: Effects of 2-mercaptopropionyl glycine on radiation-induced lipid peroxidation in liposomes and in rat liver microsomal suspensions. Int J Radiat Biol 50:323–335, 1986

    Google Scholar 

  34. Schraufstatter IU, Hyslop PA, Hinshaw DB, Spragg RG, Sklar LA, Cochrance CG: Hydrogen peroxide-induced injury of cells and its prevention by inhibitors of poly(ADP-ribose) polymerase. Proc Natl Acad Sci 83:4908–4912, 1986

    Google Scholar 

  35. Altschuld RA, Wenger WC, Lamka KG, Kindig OR, Capen CC, Mizuhira V, Vander Heide RS, Brierley GP: Structural and functional properties of adult rat heart myocytes lysed with digitonin. J Biol Chem 260:14325–14334, 1985

    Google Scholar 

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Authors and Affiliations

  1. Department of Physiology, University of Ottawa, School of Medicine, Ottawa, Ontario, Canada

    M. Kato & K. J. Kako

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  1. M. Kato
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  2. K. J. Kako
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Dr. Kato was on leave from the Department of Medicine (Prof. M. Nagano), Jikei University-Aoto Hospital, Tokyo, and was supported by the Uehara Foundation.

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Kato, M., Kako, K.J. Effects of N-(2-mercaptopropionyl)glycine on ischemic-reperfused dog kidney in vivo and membrane preparation in vitro . Mol Cell Biochem 78, 151–159 (1987). https://doi.org/10.1007/BF00229689

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  • DOI: https://doi.org/10.1007/BF00229689

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