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Updated: Jul 8, 2025

Improved Renal Denervation Mitigated Hypertension Induced by Angiotensin II Infusion
Published on: May 26, 2022
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.
Abstract:
This study examined the reno-protective potential of Compound 21 during renal ischemia-reperfusion injury by regulating the PI3K expression. 20 adult male Swiss-albino mice, aged 8-12 weeks and weighing 20-30g, were randomly assigned to four equal groups: sham, control, vehicle, and Compound 21. Serum urea, creatinine, inflammatory mediators, tissue 8-isoprostane, and myeloperoxidase were quantified using ELISA. Compared to the sham group, blood levels of urea, creatinine, TNF-α, IL-6, and IL-10 were significantly higher in the ischemia-reperfusion group than in the sham group (p<0.05). However, these indicators were significantly lower in the Compound 21 group (p<0.05). Histological analysis revealed significant renal tissue damage in the ischemia-reperfusion group (p<0.05), which was significantly reduced in the Compound 21 group (p<0.05). PCR results showed that PI3K expression was significantly lower (p<0.05) in the control group compared to the sham group but significantly higher in the Compound 21 group (p<0.05). Furthermore, P-AKT expression levels in the control group were considerably lower than in the sham group (p<0.05). On the other hand, the level of P-AKT expression in the Compound 21 group was significantly upregulated compared to the control group (p<0.05). The findings revealed that Compound 21 could mitigate renal dysfunction induced by ischemia-reperfusion injury in male mice through modulation of the PI3K/AKT signaling pathway, resulting in decreased levels of pro-inflammatory cytokines and renal oxidative stress markers.
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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