Potential nephroprotective effects of angiotensin II type 2 receptor agonist Compound 21 in renal

Lafta Fayez Kadhim1, Sarmad Nory Gany2, Heider Qassam3

  • 1Ministry of Health, Al-Najaf Health Directorate, Al-Najaf, Iraq.

PubMed

Insights

Compound 21 protects kidneys from injury by regulating the PI3K/AKT pathway. This reduces inflammation and oxidative stress, offering reno-protective effects in a mouse model of renal ischemia-reperfusion injury.

Area of Science:

  • Nephrology
  • Pharmacology
  • Molecular Biology

Background:

  • Renal ischemia-reperfusion (I/R) injury is a significant clinical challenge.
  • Understanding molecular mechanisms underlying I/R injury is crucial for developing effective treatments.
  • The PI3K/AKT signaling pathway plays a role in cellular protection and survival.

Purpose of the Study:

  • To investigate the reno-protective effects of Compound 21 in a mouse model of renal I/R injury.
  • To elucidate the role of the PI3K/AKT signaling pathway in mediating these protective effects.
  • To assess the impact of Compound 21 on inflammatory markers and oxidative stress.

Main Methods:

  • Adult male Swiss-albino mice were subjected to renal I/R injury and treated with Compound 21.
  • Serum urea, creatinine, TNF-α, IL-6, IL-10, 8-isoprostane, and myeloperoxidase were measured.
  • Renal tissue damage was assessed via histology.
  • PI3K and phosphorylated AKT (P-AKT) expression levels were analyzed using PCR.

Main Results:

  • Compound 21 significantly reduced serum urea, creatinine, and inflammatory mediators (TNF-α, IL-6, IL-10) compared to controls.
  • Histological analysis showed reduced renal tissue damage in the Compound 21 group.
  • Compound 21 upregulated PI3K and P-AKT expression, indicating activation of the PI3K/AKT pathway.
  • Levels of 8-isoprostane and myeloperoxidase were decreased by Compound 21 treatment.

Conclusions:

  • Compound 21 demonstrates significant reno-protective potential against I/R injury in mice.
  • The protective effects are mediated through the modulation of the PI3K/AKT signaling pathway.
  • Compound 21 reduces inflammation and oxidative stress, making it a promising therapeutic candidate for renal I/R injury.

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