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

by Selleckchem | Dec 23 2023

Renal ischemia-reperfusion injury is a critical clinical condition with a potentially fatal prognosis if not adequately managed. NHWD-870, a known Brd4 inhibitor with anti-cancer properties, exhibits additional attributes such as antioxidant, anti-inflammatory, and anti-apoptotic effects, suggesting its potential to preserve renal tissue and mitigate damage during ischemic insults. We aimed to assess the potential nephroprotective effect of NHWD-870 by investigating its anti-apoptotic, anti-inflammatory, and antioxidant properties in a rat model of renal ischemia-reperfusion injury. Male Wistar Albino rats (n=24) were randomly assigned to four groups: sham, control, vehicle, and NHWD-870. The control group experienced bilateral renal ischemia for 30 minutes, followed by 2 hours of reperfusion, while the sham group underwent a laparotomy without ischemia-reperfusion induction. The vehicle group received a DMSO injection, and the NHWD-870 group was administered 3mg/kg NHWD-870 orally 24 hours before repeating the control group protocol. Blood samples were collected after reperfusion for blood urea nitrogen (BUN) and serum creatinine (SCr) analysis. ELISA method was used to assess IL-1B, BCL-2, PGF-2, and PI3K/AKT signaling pathways in renal tissue. Tubular injury severity was evaluated through histopathological analysis. NHWD-870 treatment improved renal function and histological preservation compared to the control and vehicle groups. BUN, sCR, IL-1B, BCL-2, and PGF-2 levels in renal tissue were significantly improved in the NHWD-870 group (p<0.05). Furthermore, the PI3K/AKT signaling pathway was significantly upregulated (p<0.01), and tubular injury severity was reduced in the NHWD-870 group. NHWD-870 demonstrated substantial nephroprotective effects in reducing renal damage induced by ischemia-reperfusion injury in rats. These effects may be attributed to the anti-apoptotic properties, as indicated by increased levels of the anti-apoptotic protein Bcl-2, and the reduction in oxidative stress marker PGF-2 through upregulation of the PI3K/AKT signaling pathway, along with the decrease in the inflammatory marker IL-1B.

Comments:

This study exploring NHWD-870's potential in mitigating renal ischemia-reperfusion injury looks promising! The multi-faceted nature of NHWD-870, acting as a Brd4 inhibitor with anti-cancer properties, alongside its antioxidant, anti-inflammatory, and anti-apoptotic effects, seems particularly beneficial in preserving renal tissue during ischemic insults.

The experimental design with the rat model and the four groups (sham, control, vehicle, NHWD-870) offers a robust platform for assessment. The administration of NHWD-870 24 hours prior to inducing ischemia-reperfusion injury is an interesting approach, likely allowing the compound to exert its effects and potentially pre-condition the tissue against the injury.

The improvements in renal function and histological preservation observed in the NHWD-870 group compared to the control and vehicle groups, as indicated by the significant changes in BUN, sCR, IL-1B, BCL-2, and PGF-2 levels, are significant findings. The upregulation of the PI3K/AKT signaling pathway, known for its role in cell survival and growth, further supports the nephroprotective effects of NHWD-870.

The correlation between the decrease in tubular injury severity and the observed changes in biomarkers suggests a promising avenue for potential clinical applications. This compound's ability to modulate multiple pathways involved in apoptosis, oxidative stress, and inflammation showcases its potential as a therapeutic agent for managing renal ischemia-reperfusion injury.

Overall, this study's findings suggest that NHWD-870 holds promise as a nephroprotective agent, but further research, particularly in clinical settings or larger animal models, would be crucial to validate its efficacy and safety for human use.