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Therapeutic strategies of redox modification for renal failure

Research Project

Project/Area Number 13670789
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionFukui Medical University

Principal Investigator

TSUKAHARA Hirokazu  Fukui Medical University, Faculty of Medicine, Assistant Professor, 医学部附属病院, 講師 (90207340)

Co-Investigator(Kenkyū-buntansha) HATA Ikue  Fukui Medical University, Faculty of Medicine, Research Associate, 医学部, 助手 (50251997)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsRenal failure / Redox modification / Oxidative stress / Reactive oxygen species / Reactive nitrogen species / Gas biology
Research Abstract

Renal failure is a syndrome characterized by an abrupt, in most cases, reversible kidney dysfunction, or a progressive, in most cases, irreversible kidney dysfunction. The spectrum of inciting factors is broad, and the pathophysiology of renal failure includes endothelial, glomerular and tubular dysfunction, which vary in severity and time of appearance. The present project was designed to examine the contribution of oxidative and nitrosative stress to the renal damage in vivo and in vitro situations. The results obtained with this project are the following.
(1) We have demonstrated using the rat model of acute renal failure that L-Nil (inducible NO synthase inhibitor), lecithinized SOD, and ebselen (scavenger of peroxynitrite) treatments improve renal function due to their suppression of peroxynitrite production or its scavenging, consequently preventing lipid peroxidation and oxidative DNA damage.
(2) We have found that the methylenetetrahy drofolate reductase (MTHFR) TT genotype may b … More e associated with early development and progression of childhood segmental glomerulosclerosis.
(3) We examined whether advanced glycosylation end product (AGE) production and oxidative stress are augmented in young patients with type 1 diabetes at early clinical stages of the disease. The results have indicated that accumulation of AGEs, whose formation is closely linked to oxidative stress, and resultant endothelial dysfunction may start early in the course of type 1 diabetes.
(4) We examined the effect of NO on the adhesion of human microvascular endothelial cells using the ECIS technique. The results have suggested that NO modulates cell-matrix and/or cell-cell adhesion in endothelial cells and that this molecule might modify microvascular permeability in human tissues and organs.
(5) We have reviewed basic chemical aspects of the oxidation and disproportionation of NO, and also established the formulas for reliably predicting NO_2 or N_2O formation in any set of NO (with O_2) and in any time. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Noiri E, et al.: "Oxidative and nitrosative stress in acute renal ischemia"Am J Physiol Renal Physiol. 281. 948-957 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zou C, et al.: "Methylenetetrahydrofolate reductase polymorphism in childhood focal segmental glomerulosclerosis"Nephron. 92(2). 449-451 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsukahara H, et al.: "Oxidant and antioxidant activities in childhood meningitis"Life Sci. 71(23). 2797-2806 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsukahara H, et al.: "Gas-phase oxidation and disproportionation of nitric oxide"Methods Enzymol. 359. 168-179 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsukahara H, et al.: "Gas-phase disproportionation of nitric oxide in elevated pressures"Free Radic Res. 37(2). 171-177 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noiri E, Nakao A, Uchida K, Tsukahara H, Ohno M, Fujita T, Brodsky S, Goligorsky MS: "Oxidative and nitrosative stress in acute renal ischemia"Am J Physiol. 281(5). F948-957 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsukahara H: "Pathophysiological roles of nitric oxide in inflammatory diseases"Current Advances in Pediatric Asthma and Other Allergic Diseases. (Morikawa A, ed ; Jomo Newspaper). 145-152 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hattori K, Tsuchida S, Tsukahara H, Mayumi M, Tanaka T, Zhang L, Taniguchi T, Muramatsu I: "Augmentation of NO-mediated vasodilation in metabolic acidosis"Life Sci. 71(12). 1439-1447 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsukahara H, Haruta T, Todoroki Y, Hiraoka M, Noiri E, Maeda M, Mayumi M: "Oxidant and antioxidant activities in childhood meningitis"Life Sci. 71(23). 2797-2806 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zou C, Tsukahara H, Hiraoka M, Mizu J, Todoroki Y, Ohshima Y, Kimura H, Tsuzuki K, Mayumi M: "Methylenetetrahydrofolate reductase polymorphism in childhood primary focal segmental glomerulosclerosis"Nephron. 92(2). 449-451 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsukahara H, Ishida T, Mayumi M: "Gas-phase oxidation and disproportionation of nitric oxide"Methods Enzymol. (Cadenas E, Packer L, eds ; Academic Press) 359. 168-179 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsukahara H, Ishida T, Todoroki Y, Hiraoka M, Mayumi M: "Gas-phase disproportionation of nitric oxide at elevated pressures"Free Radic Res. 37(2). 171-177 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsukahara H, Shibata R, Ohshima Y, Todoroki Y, Sato S, Ohta N, Hiraoka M, Yoshida A, Nishima S, Mayumi M: "Oxidative stress and altered antioxidant defenses in children with acute exacerbation of atopic dermatitis"Life Sci. 72(22). 2509-2516 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsukahara H, Sekine K, Uchiyama M, Kawakami H, Hata I, Todoroki Y, Hiraoka M, Kaji M, Yorifuji T, Momoi T, Yoshihara K, Beppu M, Mayumi M: "Formation of advanced glycosylation end products and oxidative stress in young patients with type 1 diabetes"Pedaitr Res. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsukahara H, Shibata R, Ohta N, Y, Sato S, Hiraoka M, Ito S, Nishima S, Mayumi M: "Increased pentosidine, an advanced glycation endproduct, in urine from children with acute exacerbation of atopic dermatitis and its relation with oxidative stress"Metabolism. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hattori K, et al.: "Augmentation of NO-mediated vasodilation in metabolic acidosis"Life Sci. 71(12). 1439-1447 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Zou C, et al.: "Methylenetetrahydrofolate reductase polymorphism in childhood focal segmental glomerulosclerisis"Nephron. 92(2). 449-451 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsukahara H, et al.: "Oxidant and antioxidant activities in childhood meningitis"Life Sci. 71(23). 2797-2806 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsukahara H., et al.: "Gas-phase oxidation and disproportionation of nitric oxide"Methods Enzymol. 359. 168-179 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsukahara H, et al.: "Gas-phase disproportionation of nitric oxide in elevated pressures"Free Radic Res. 37(2). 171-177 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Noiri E, Nakao A, Uchida K, et al.(Tsukahara Hは4人目): "Oxidative and nitrosative stress in acute renal ischemia"AmJPhysiol Renal Physiol. 281. 948-957 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hori C, Hiraok M, Yoshikawa N, et al.(Tsukahara Hは8人目): "Significance of ACE genotypes and medical treatment in childhood focal glomerulosclerosis"Nephron. 88. 313-319 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hata I, Shigematsu Y, Ohshima Y, et al.(Tsukahara Hは4人目): "Involvement of thioredoxin in the regulation of growth homone secretion in ratpituitary cell cultures"AmJPhysiol Endocrinol Metab. 281. 269-274 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Omata N, Tsukahara H, Ito S, et al.(Tsukahara Hは2人目): "Increased oxidative stress in childhood atopic dermatitis"Life Sci. 69. 223-228 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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