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

Debra Dorotea, Guideock Kwon, Jung Hwa Lee, Erika Saunders, Yun Soo Bae, Sung Hwan Moon, Soo Jin Lee, Dae-Ryong Cha, Hunjoo Ha

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7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)180-189
Number of pages10
JournalPharmacology
Volume102
Issue number3-4
DOIs
Publication statusPublished - 2018 Sep 1

Keywords

  • APX-115
  • Diabetic kidney disease
  • NADPH oxidases
  • Oxidative stress
  • pan-NADPH oxidases inhibitor

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Dorotea, D., Kwon, G., Lee, J. H., Saunders, E., Bae, Y. S., Moon, S. H., Lee, S. J., Cha, D-R., & Ha, H. (2018). A pan-NADPH Oxidase Inhibitor Ameliorates Kidney Injury in Type 1 Diabetic Rats. Pharmacology, 102(3-4), 180-189. https://doi.org/10.1159/000491398