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A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion
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Published on: February 2, 2021

Combined Apocynin and Novokinin Treatment Attenuates Renal Damage and Reduces KIM-1 Expression in a Model of Ischemic

Milan Ivanov1, Nevena Mihailović-Stanojević1, Una-Jovana Vujačić1

  • 1Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Dr Subotića 4, 11000 Belgrade, Serbia.

International Journal of Molecular Sciences
|July 28, 2026
PubMed

Insights

Targeting both NADPH oxidase and angiotensin II type 2 receptors may offer a promising therapeutic strategy for kidney ischemia-reperfusion injury (IRI). Combined treatment significantly reduced kidney injury and oxidative stress in a rat model.

Area of Science:

  • Nephrology
  • Cardiovascular Research
  • Oxidative Stress

Background:

  • Kidney ischemia-reperfusion injury (IRI) is a significant clinical challenge with incompletely understood mechanisms.
  • NADPH oxidase and angiotensin II type 2 receptors (AT2R) are implicated in the pathogenesis of ischemic acute kidney injury (AKI).

Purpose of the Study:

  • To investigate the therapeutic effects of apocynin (APO), an NADPH oxidase inhibitor, and novokinin (NOV), an AT2R agonist, on kidney IRI in spontaneously hypertensive rats (SHR).
  • To evaluate the combined efficacy of APO and NOV in mitigating kidney damage and oxidative stress.

Main Methods:

  • Spontaneously hypertensive rats (SHR) underwent induced kidney IRI and were divided into five groups: Sham-operated, AKI, and AKI treated with APO, NOV, or both.
  • Renal function, kidney injury molecule-1 (KIM-1) levels, and oxidative stress markers were assessed.

Main Results:

  • All treatments showed slight improvements in renal function.
  • The combination of APO and NOV significantly reduced KIM-1 levels and oxidative stress compared to the control AKI group.
  • Additive effects were observed when targeting both NADPH oxidase and AT2R.

Conclusions:

  • Combined inhibition of NADPH oxidase and AT2R activation offers superior therapeutic benefits for kidney IRI than individual treatments.
  • This dual-targeting strategy presents a potentially promising approach for managing AKI in critically ill patients.
Keywords:
NADPH oxidaseacute kidney injuryangiotensin II type 2 receptorapocyninhypertensionkidney injury molecule-1novokinin

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