A pan-NADPH Oxidase Inhibitor Ameliorates Kidney Injury in Type 1 Diabetic Rats
- 주제(키워드) Diabetic kidney disease , pan-NADPH oxidases inhibitor , APX-115 , NADPH oxidases , Oxidative stress
- 주제(기타) Pharmacology & Pharmacy
- 설명문(일반) [Dorotea, Debra; Kwon, Guideock; Lee, Jung Hwa; Ha, Hunjoo] Ewha Womans Univ, Coll Pharm, Grad Sch Pharmaceut Sci, 52 Ewhayeodae Gil, Seoul 120750, South Korea; [Saunders, Erika] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA; [Bae, Yun Soo] Ewha Womans Univ, Dept Life Sci, Seoul, South Korea; [Moon, Sung Hwan; Lee, Soo Jin] Aptabio Therapeut Inc, Yongin, South Korea; [Cha, Dae Ryong] Korea Univ, Ansan Hosp, Dept Nephrol, Ansan, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 KARGER
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000159806
- 본문언어 영어
- Published As http://dx.doi.org/10.1159/000491398
초록/요약
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
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