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Effect of a novel free radical scavenger, edaravone, on puromycin aminonucleoside induced nephrosis in rats

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Abstract

Recent studies indicate that excessive production of oxidants plays a role in the pathogenesis of glomerular injury leading to proteinuria in patients with minimal-change nephrotic syndrome (MCNS). The novel free radical scavenger, edaravone (EDA), which was recently developed in Japan, is currently used in patients with stroke. We studied whether this new agent would be beneficial in patients with MCNS by its antioxidant activity and examined its effect on proteinuria in nephrosis induced by puromycin-aminonucleoside (PAN) in rats. Nineteen Wistar-Kyoto rats injected with PAN were assigned to four groups: group 1, without EDA (n=4); group 2, concomitant EDA injection from 1 day prior to PAN administration (n=5); group 3, concomitant EDA injection from 1 day after PAN administration (n=5); group 4, concomitant EDA injection from 3 days after PAN administration (n=5). Daily urinary excretions of protein and 8-hydroxy-2’-deoxyguanosine (8-OHdG), a new sensitive marker of oxidative DNA damage in vivo, were measured in each group from the 1st to the 30th day after PAN injection. In group 1 proteinuria developed from the 5th day and reached the peak level on the 9th day. In groups 2, 3, and 4 proteinuria did not appear until the 6th day. The excretions in urinary protein and 8-OHdG were significantly lower in groups 2, 3, and 4 than group 1 on days 5, 9, and 25. In conclusion, EDA could delay and ameliorate the urinary protein excretion in accordance with the urinary 8-OHdG excretion in PAN-induced nephrosis.

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References

  1. Shalhoub RJ (1974) Pathogenesis of lipid nephrosis: a disorder of T-cell function. Lancet II:556–560

    Article  Google Scholar 

  2. Fiser RT, Arnold WC, Charlton RK, steele RW, Childress SH, Shirkey B (1991) T-lymphocyte subsets in nephrotic syndrome. Kidney Int 40:913–916

    PubMed  Google Scholar 

  3. Nunez-Roldan A, Villechenous E, Fernandez-Andrade C, Martin-Govantes J (1982) Increased HLA-DR7 and decreased DR2 in steroid-responsive nephrotic syndrome. N Engl J Med 306:366–367

    Google Scholar 

  4. Diamond JR (1992) The role of reactive oxygen species in animal models of glomerular disease. Am J Kidney Dis 19:292–300

    PubMed  Google Scholar 

  5. Raats CJI, Bakker MAH, Van den Born J, Berden JHM (1997) Hydroxyl radicals depolymerize glomerular heparin sulfate in vitro and in experimental nephrotic syndrome. J Biol Chem 272:26734–26741

    Article  PubMed  Google Scholar 

  6. Thakur V, Walker PD, Shah SV (1988) Evidence suggesting a role for hydroxyl radical in puromycin aminonucleoside-induced proteinuria. Kidney Int 34:494–499

    PubMed  Google Scholar 

  7. Kinra S, Rath B, Kabi BC (2000) Indirect quantification of lipid peroxidation in steroid responsive nephrotic syndrome. Arch Dis Child 82:76–78

    Article  PubMed  Google Scholar 

  8. Turi S, Nemeth I, Torkos A, Saghy L, Varga I, Matkovics B, Nagy J (1997) Oxidative stress and antioxidant defense mechanism in glomerular diseases. Free Radic Biol Med 22:161–168

    Article  PubMed  Google Scholar 

  9. Fydryk J, Jacobson E, Kurzawska O, Malecka G, Gonet B, Urasinski T, Brodkiewicz A, Bukowska H (1998) Antioxidant status of children with steroid-sensitive nephrotic syndrome. Pediatr Nephrol 12:751–754

    Article  PubMed  Google Scholar 

  10. Guidet BR, Sudhir SV (1989) In vivo generation of hydrogen peroxide by rat kidney cortex and glomeruli. Am J Physiol 256:F158–F164

    PubMed  Google Scholar 

  11. Baud L, Ardaillou R (1986) Reactive oxygen spiecies: production and role in the kidney. Am J Physiol 251:F765–F776

    PubMed  Google Scholar 

  12. Yoshioka T, Ichikawa I, Fogo A (1991) Reactive oxygen metabolites cause massive, reversible proteinuria and glomerular sieving defect without apparent ultrastructural abnormality. J Am Soc Nephrol 2:902–912

    PubMed  Google Scholar 

  13. Doi K, Suzuki Y, Nakao A, Fujita T, Noiri E (2004) Radical scavenger edaravone developed for clinical use ameliorates ischemia/reperfusion injury in rat kidney. Kidney Int 65:1714–1723

    Article  PubMed  Google Scholar 

  14. Edaravone Acute Infarction Study Group (2003) Effect of a novel free radical scavenger, edaravone (MCI-186), on acute brain infarction. Randomized, placebo-controlled, double-blind study at multicenters. Cerebrovasc Dis 15:222–229

    Article  PubMed  Google Scholar 

  15. Lannigan R, Kark R, Pollak VE (1962) The effect of a single intravenous injection of aminonucleoside of puromycin on the rat kidney: a-light and electron-microscope study. J Pathol Bacteriol 83:357–362

    Article  PubMed  Google Scholar 

  16. Diamond JR, Bonventre JV, Karnovsky MJ (1986) A role for oxygen free radicals in aminonucleoside nephrosis. Kidney Int 29:478–483

    PubMed  Google Scholar 

  17. Shigenaga MK, Ames BN (1991) Assays for 8-hydroxy-2’-deoxyguanosine: a biomarker of in vivo oxidative DNA damage. Free Radic Biol Med 10:211–216

    Article  PubMed  Google Scholar 

  18. Fraga CG, Shigenaga MK, Park JW, Degan P, Ames BN (1990) Oxidative damage to DNA during aging: 8-hydroxy-2’-deoxyguanosine in rat organ DNA and urine. Proc Natl Acad Sci USA 87:4533–4537

    PubMed  Google Scholar 

  19. Toyokuni S, Tanaka T, Hattori Y, Nishiyama Y, Yoshida A, Uchida K, Hiai H, Ochi H, Osawa T (1997) Quantitative immunohistochemical determination of 8-hydroxy-2’-deoxyguanosine by a monoclonal antibody N45.1: its application to ferric nitrilotriacetate-induced renal carcinogenesis model. Lab Invest 76:365–374

    PubMed  Google Scholar 

  20. Saito S, Yamauchi H, Hasui Y, Kurashige J, Ochi H, Yoshida K (2000) Quantitive determination of 8-hydroxy-2’-deoxyguanosine (8-OH-dg) by using ELISA. Res Commun Mol Pathol Pharmacol 107:39–44

    PubMed  Google Scholar 

  21. Fawcett JP, Jiang R, Walker RJ (1994) Time course of lipid peroxidation in puromycin aminonucleoside-induced nephropathy. Res Commun Mol Pathol Pharmacol 86:227–234

    PubMed  Google Scholar 

  22. Ricardo SD, Bertram JF, Ryan GB (1994) Antioxidants protect podocyte foot processes in puromycin aminonucleoside-treated rats. J Am Soc Nephrol 4:1974–1986

    PubMed  Google Scholar 

  23. Abe K, Yuki S, Kogure K (1988) Strong attenuation of ischemic and postischemic brain edema in rats by a novel free radical scavenger. Stroke 19:480–485

    PubMed  Google Scholar 

  24. Watanabe T, Yuki S, Egawa M, Nishi H (1994) Protective effects of MCI-186 on cerebral ischemia: possible involvement of free radical scavenging and antioxidant actions. J Pharmacol Exp Ther 268:1597–1604

    PubMed  Google Scholar 

  25. Satoh M, Kashihara N, Fujimoto S, Horike H, Tokura T, Namikoshi T, Sasaki T, Makino H (2003) A novel free radical scavenger, edaravone, protects against Cisplatin-induced acute renal damage in vitro and in vivo. J Pharmacol Exp Ther 305:1183–1190

    Article  PubMed  Google Scholar 

  26. Kono H, Asakawa M, Fujii H, Maki A, Amemiya H, Yamamoto M, Matsuda M, Matsumoto Y (2003) Edaravone, a novel free radical scavenger, prevents liver injury and mortality in rats administered endotoxin. J Pharmacol Exp Ther 307:74–82

    Article  PubMed  Google Scholar 

  27. Minhaz U, Tanaka M, Tsukamoto H, Watanabe K, Koide S, Shohtsu A, Nakazawa H (1996) Effect of MCI-186 on postischemic reperfusion injury in isolated rat heart. Free Radic Res 24:361–367

    PubMed  Google Scholar 

  28. Kawachj H, Koike H, Kurihara H, Sakai T, Shimizu F (2003) Cloning of rat homologue of podocin: expression in proteinuric states and in developing glomeruli. J Am Soc Nephrol 14:46–56

    Article  PubMed  Google Scholar 

  29. Lee YK, Kwon T, Kim DJ, Huh W, Kim YG, Oh HY, Kawachi H (2004) Ultrastructural study on nephrin expression in experimental puromycin aminonucleoside nephrosis. Nephrol Dial Transplant 19:2981–2986

    Article  PubMed  Google Scholar 

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Correspondence to Kazunari Kaneko.

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Someya, T., Kaneko, K., Yamada, T. et al. Effect of a novel free radical scavenger, edaravone, on puromycin aminonucleoside induced nephrosis in rats. Pediatr Nephrol 20, 1430–1434 (2005). https://doi.org/10.1007/s00467-005-1959-9

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  • DOI: https://doi.org/10.1007/s00467-005-1959-9

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