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A pan-NADPH Oxidase Inhibitor Ameliorates Kidney Injury in Type 1 Diabetic Rats

Title
A pan-NADPH Oxidase Inhibitor Ameliorates Kidney Injury in Type 1 Diabetic Rats
Authors
Dorotea, DebraKwon, GuideockLee, Jung HwaSaunders, ErikaBae, Yun SooMoon, Sung HwanLee, Soo JinCha, Dae RyongHa, Hunjoo
Ewha Authors
배윤수하헌주
SCOPUS Author ID
배윤수scopus; 하헌주scopus
Issue Date
2018
Journal Title
PHARMACOLOGY
ISSN
0031-7012JCR Link

1423-0313JCR Link
Citation
PHARMACOLOGY vol. 102, no. 3-4, pp. 180 - 189
Keywords
Diabetic kidney diseasepan-NADPH oxidases inhibitorAPX-115NADPH oxidasesOxidative stress
Publisher
KARGER
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Background: NADPH oxidases (Nox) is a major enzyme system contributing to oxidative stress, which plays an important role in the pathogenesis of diabetic kidney disease (DKD). We have shown an elevation of renal Nox1, Nox2, and Nox4 in diabetic mice. APX-115, a pan-Nox inhibitor, attenuated the progression of DKD in mice. As the standard diabetic mice cannot fully mimic human DKD, the present study was aimed to show the dose-dependent effect and to provide a confirmatory evidence of APX-115 in attenuating DKD in diabetic rats. Method: Type 1 diabetes was induced by a single 60 mg/kg intraperitoneal injection of streptozotocin in Sprague-Dawley rats. 0.5, 5, or 30 mg APX-115/kg/day or losartan 1 mg/kg/day were administered orally to diabetic rats for 8 weeks. Results: APX-115 treatment showed an improvement in kidney function and tubular and podocyte injury, as well as attenuation of inflammation, fibrosis, and oxidative stress as much as losartan, a comparative drug and mainstay treatment in DKD. Therapeutic effect of APX-115 was exhibited in a dose-dependent manner; a dose of 30 mg/kg displayed a superior efficacy. Conclusion: This finding verified the pre-clinical data of APX-115 in protecting against DKD, which is important to bring APX-115 toward the next stage of drug development. (C) 2018 S. Karger AG, Basel
DOI
10.1159/000491398
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약학대학 > 약학과 > Journal papers
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