NHWD-870 protects the kidney from ischemia/reperfusion injury by upregulating the PI3K/AKT signaling pathway

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Saba Sahib Younis1, Fadhaa Abdul Ameer Ghafil2, Sahar Majeed2

  • 1Al-Sadr Medical City, Al-Najaf Health Directorate, Al Najaf Al-Ashraf, Iraq.

Journal of Medicine and Life
|September 7, 2023
PubMed

Insights

NHWD-870, a Brd4 inhibitor, shows significant nephroprotective effects against renal ischemia-reperfusion injury in rats. It reduces kidney damage by decreasing inflammation and oxidative stress, preserving renal function and tissue integrity.

Area of Science:

  • Nephrology
  • Pharmacology
  • Molecular Biology

Background:

  • Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury.
  • NHWD-870, a Brd4 inhibitor, possesses antioxidant, anti-inflammatory, and anti-apoptotic properties.
  • These properties suggest NHWD-870's potential for mitigating IRI-induced renal damage.

Purpose of the Study:

  • To evaluate the nephroprotective effects of NHWD-870 in a rat model of renal IRI.
  • To investigate the underlying anti-apoptotic, anti-inflammatory, and antioxidant mechanisms of NHWD-870.

Main Methods:

  • Male Wistar Albino rats were subjected to 30 minutes of bilateral renal ischemia and 2 hours of reperfusion.
  • NHWD-870 (3mg/kg) was administered orally 24 hours prior to the IRI procedure.
  • Renal function was assessed by blood urea nitrogen (BUN) and serum creatinine (SCr).
  • Inflammatory marker (IL-1β), apoptotic markers (Bcl-2), oxidative stress marker (PGF-2), and PI3K/AKT pathway were analyzed using ELISA.
  • Renal tissue damage was evaluated through histopathology.

Main Results:

  • NHWD-870 treatment significantly improved renal function, indicated by reduced BUN and SCr levels.
  • Histopathological analysis revealed reduced tubular injury severity in the NHWD-870 group.
  • NHWD-870 administration led to decreased levels of IL-1β and PGF-2, and increased Bcl-2 levels in renal tissue.
  • The PI3K/AKT signaling pathway was significantly upregulated following NHWD-870 treatment.

Conclusions:

  • NHWD-870 demonstrates significant nephroprotective effects against renal IRI in rats.
  • These protective effects are likely mediated by its anti-apoptotic (via Bcl-2), anti-inflammatory (via IL-1β reduction), and antioxidant (via PGF-2 reduction) properties.
  • Upregulation of the PI3K/AKT pathway contributes to the observed renoprotection by NHWD-870.
Keywords:
AKI: Acute Kidney InjuryBCL-2BCL-2: B-cell lymphoma-2BUN: Blood Urea NitrogenDMSO: Dimethyl SulfoxideELISA: Enzyme-Linked Immunosorbent AssayI/R: Ischemia ReperfusionIL-1BIL-1B: Interleukin-1 BetaNHWD-870P-Akt: Phosphorylated-Protein Kinase BPGF-2PI3K/AKTPI3K: Phosphatidylinositide 3-KinasesRIRI: Renal Ischemia-Reperfusion InjuryROS: Reactive Oxygen SpeciesSCr: Serum Creatinineischemia reperfusion injury

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