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，其特征是在大多数情况下突然发生，可逆肾功能障碍或进行性肾脏功能障碍，在大多数情况下，不可逆的肾功能障碍。煽动因素的光谱很广，肾衰竭的病理生理包括内皮，肾小球和管状功能障碍，其严重程度和外观时间各不相同。本项目旨在检查氧化和亚硝化应激对体内肾脏损伤和体外情况的贡献。通过该项目获得的结果如下。（1）我们已经使用急性肾衰竭的大鼠模型证明了l-nil（可诱导的无合酶抑制剂），lecithinized SOD和EBSLEN和EBSLEN（过氧亚硝酸盐的清除剂）改善肾功能，从而改善了肾脏功能，从而抑制了多氧化剂的生产或驱动性的驱动性，并导致了其驱动的效果，并导致了其遗传性的降低。 （2）我们发现，甲基元素甲基二氢干燥酸（MTHFR）tt基因型可能会与早期发育和儿童期分段性肾小球硬化症的早期发展和进展有关。结果表明，年龄的积累，其形成与氧化应激密切相关，最终的内皮功能障碍可能在1型糖尿病的过程中开始。（4）我们使用ECIS技术检查了NO对人类微血管内皮细胞粘附的影响。结果表明，NO在内皮细胞中调节细胞 - 垫和/或细胞细胞粘合剂，并且该分子可能会改变人体组织和器官中的微血管渗透性。（5）我们已经审查了NO的氧化和氧化和不成比例的基本化学方面，并且还建立了no__2或NO__2或NO_2或NO_2O _2o的形式（任何时间。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, 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。

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。

Hattori K, et al.: "Augmentation of NO-mediated vasodilation in metabolic acidosis"Life Sci. 71(12). 1439-1447 (2002)

Hattori K 等人：“代谢性酸中毒中 NO 介导的血管舒张的增强”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。