Therapeutic strategies of redox modification for renal failure

氧化还原修饰治疗肾衰竭的策略

• 批准号: 13670789
• 负责人: TSUKAHARA Hirokazu
• 金额: $ 1.92万
• 依托单位: Fukui Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670789/
• 关键词: Renal failure; Redox modification; Oxidative stress; Reactive oxygen species; Reactive nitrogen species; Gas biology

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

肾衰竭是一种综合征，其特征是突然的（在大多数情况下）可逆性肾功能障碍，或进行性（在大多数情况下）不可逆的肾功能障碍。诱发因素范围广泛，肾衰竭的病理生理学包括内皮、肾小球和肾小管功能障碍，其严重程度和出现时间各不相同。本项目旨在研究氧化和亚硝化应激对体内和体外肾损伤的影响。该项目获得的结果如下。(1) 我们使用急性肾衰竭大鼠模型证明，L-Nil（诱导型 NO 合酶抑制剂）、卵磷脂化 SOD 和依布硒啉（过氧亚硝酸盐清除剂）治疗可改善肾功能，因为它们抑制过氧亚硝酸盐的产生或清除，从而防止脂质过氧化和氧化 DNA (2) 我们发现亚甲基四氢叶酸还原酶 (MTHFR) TT 基因型可能与儿童节段性肾小球硬化症的早期发展和进展相关。(3) 我们检查了年轻 1 型糖尿病患者在疾病早期临床阶段是否会增加晚期糖基化终产物 (AGE) 的产生和氧化应激。结果表明，AGEs的积累（其形成与氧化应激密切相关）以及由此产生的内皮功能障碍可能在1型糖尿病病程的早期就开始了。（4）我们使用ECIS技术检查了NO对人微血管内皮细胞粘附的影响。结果表明，NO调节内皮细胞中的细胞-基质和/或细胞-细胞粘附，并且该分子可能改变人体组织和器官中的微血管通透性。(5)我们回顾了NO氧化和歧化的基本化学方面，并建立了可靠预测任何NO组（与O_2）和中NO_2或N_2O形成的公式。 任何时候。较少的

项目成果

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

Noiri E 等人：“急性肾缺血中的氧化和亚硝化应激”Am J Physiol Renal Physiol。

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)

Tsukahara H：“一氧化氮在炎症性疾病中的病理生理作用”小儿哮喘和其他过敏性疾病的最新进展。

Tsukahara H, et al.: "Oxidant and antioxidant activities in childhood meningitis"Life Sci. 71(23). 2797-2806 (2002)

Tsukahara H 等人：“儿童脑膜炎中的氧化剂和抗氧化活性”生命科学。

Zou C, et al.: "Methylenetetrahydrofolate reductase polymorphism in childhood focal segmental glomerulosclerisis"Nephron. 92(2). 449-451 (2002)

Zou C，等人：“儿童局灶节段性肾小球硬化症中的亚甲基四氢叶酸还原酶多态性”肾单位。

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)

Tsukahara H、Ishida T、Todoroki Y、Hiraoka M、Mayumi M.：“高压下一氧化氮的气相歧化。”自由基研究。