A novel pan-Nox inhibitor, APX-115, protects kidney injury in streptozotocin-induced diabetic mice: Possible role of peroxisomal and mitochondrial biogenesis

Guideock Kwon, Md Jamal Uddin, Gayoung Lee, Songling Jiang, Ahreum Cho, Jung Hwa Lee, Sae Rom Lee, Yun Soo Bae, Sung Hwan Moon, Soo Jin Lee, Dae-Ryong Cha, Hunjoo Ha

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are increasingly recognized as a key factor in inflammation and extracellular matrix accumulation in diabetic kidney disease. APX-115 (3-phenyl-1-(pyridin-2-yl)-4-propyl-1-5- hydroxypyrazol HCl) is a novel orally active pan-Nox inhibitor. The objective of this study was to compare the protective effect of APX-115 with a renin-angiotensin system inhibitor (losartan), the standard treatment against kidney injury in diabetic patients, on streptozotocin (STZ)-induced diabetic kidney injury. Diabetes was induced by intraperitoneal injection of STZ at 50 mg/kg/day for 5 days in C57BL/6J mice. APX-115 (60 mg/kg/day) or losartan (1.5 mg/kg/day) was administered orally to diabetic mice for 12 weeks. APX-115 effectively prevented kidney injury such as albuminuria, glomerular hypertrophy, tubular injury, podocyte injury, fibrosis, and inflammation as well as oxidative stress in diabetic mice, similar to losartan. In addition, both APX-115 and losartan treatment effectively inhibited mitochondrial and peroxisomal dysfunction associated with lipid accumulation. Our data suggest that APX-115, a pan-Nox inhibitor, may become a novel therapeutic agent against diabetic kidney disease by maintaining peroxisomal and mitochondrial fitness.

Original languageEnglish
Pages (from-to)74217-74232
Number of pages16
JournalOncotarget
Volume8
Issue number43
DOIs
Publication statusPublished - 2017 Jan 1

Fingerprint

NADPH Oxidase
Organelle Biogenesis
Streptozocin
Losartan
Kidney
Wounds and Injuries
Diabetic Nephropathies
Inflammation
Podocytes
Albuminuria
Renin-Angiotensin System
Intraperitoneal Injections
Inbred C57BL Mouse
Hypertrophy
Extracellular Matrix
Reactive Oxygen Species
Oxidative Stress
Fibrosis
Therapeutics
Lipids

Keywords

  • APX-115
  • Diabetic kidney disease
  • Mitochondria and peroxisome
  • Oxidative stress
  • pan-Nox inhibitor

ASJC Scopus subject areas

  • Oncology

Cite this

A novel pan-Nox inhibitor, APX-115, protects kidney injury in streptozotocin-induced diabetic mice : Possible role of peroxisomal and mitochondrial biogenesis. / Kwon, Guideock; Uddin, Md Jamal; Lee, Gayoung; Jiang, Songling; Cho, Ahreum; Lee, Jung Hwa; Lee, Sae Rom; Bae, Yun Soo; Moon, Sung Hwan; Lee, Soo Jin; Cha, Dae-Ryong; Ha, Hunjoo.

In: Oncotarget, Vol. 8, No. 43, 01.01.2017, p. 74217-74232.

Research output: Contribution to journalArticle

Kwon, Guideock ; Uddin, Md Jamal ; Lee, Gayoung ; Jiang, Songling ; Cho, Ahreum ; Lee, Jung Hwa ; Lee, Sae Rom ; Bae, Yun Soo ; Moon, Sung Hwan ; Lee, Soo Jin ; Cha, Dae-Ryong ; Ha, Hunjoo. / A novel pan-Nox inhibitor, APX-115, protects kidney injury in streptozotocin-induced diabetic mice : Possible role of peroxisomal and mitochondrial biogenesis. In: Oncotarget. 2017 ; Vol. 8, No. 43. pp. 74217-74232.
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