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

Debra Dorotea1, Guideock Kwon1, Jung Hwa Lee1

  • 1Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, Republic of Korea.

Pharmacology
|August 13, 2018
PubMed
Abstract

Insights

The novel pan-Nox inhibitor APX-115 effectively treats diabetic kidney disease (DKD) in rats, showing dose-dependent improvements in kidney function and reduced injury. This confirms APX-115

Area of Science:

  • Nephrology
  • Pharmacology
  • Oxidative Stress Research

Background:

  • NADPH oxidases (Nox) contribute to oxidative stress in diabetic kidney disease (DKD) pathogenesis.
  • Renal Nox1, Nox2, and Nox4 are elevated in diabetic conditions.
  • Previous studies indicated APX-115, a pan-Nox inhibitor, attenuates DKD in mice.

Purpose of the Study:

  • To investigate the dose-dependent effects of APX-115 in a rat model of DKD.
  • To provide confirmatory evidence for APX-115's efficacy in attenuating DKD progression.

Main Methods:

  • Type 1 diabetes was induced in Sprague-Dawley rats using streptozotocin.
  • Diabetic rats received oral administration of APX-115 (0.5, 5, or 30 mg/kg/day) or losartan (1 mg/kg/day) for 8 weeks.

Main Results:

  • APX-115 improved kidney function, reduced tubular and podocyte injury, and attenuated inflammation, fibrosis, and oxidative stress.
  • The therapeutic effects of APX-115 were dose-dependent, with 30 mg/kg showing superior efficacy.
  • APX-115 demonstrated comparable efficacy to losartan, a standard DKD treatment.

Conclusions:

  • APX-115 demonstrates significant protective effects against DKD in a rat model.
  • These findings validate pre-clinical data and support advancing APX-115 to further drug development stages.
Keywords:
APX-115Diabetic kidney diseaseNADPH oxidasesOxidative stresspan-NADPH oxidases inhibitor

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