Azilsartan Modulates HMGB1/NF-κB/p38/ERK1/2/JNK and Apoptosis Pathways during Renal Ischemia Reperfusion Injury

Area of Science:

• Nephrology
• Pharmacology

Background:

• Renal ischemia/reperfusion (IR) injury is a critical condition causing kidney damage.
• Azilsartan, an angiotensin receptor blocker, is used for hypertension management.

Purpose of the Study:

• To investigate the molecular mechanisms of azilsartan's nephroprotective effects against renal IR injury in a rat model.
• To evaluate azilsartan's impact on oxidative stress, inflammation, apoptosis, and specific signaling pathways.

Main Methods:

• Rats were divided into Sham, Azilsartan, IR, and IR/Azilsartan groups.
• Histological and biochemical analyses were performed.
• Levels of key proteins (KIM-1, HMGB1, caspase 3, GPX, SOD, NF-κB, p53) and gene expression (IL-1β, IL6, IL10, TNF-α, NF-κB, p53, bax) were measured.
• Western blotting assessed p38, JNK, and ERK1/2 protein expression.

Main Results:

• IR injury led to kidney damage, elevated creatinine, BUN, inflammatory markers, and apoptosis indicators.
• IR also increased oxidative stress markers and activated NF-κB and p53 signaling pathways.
• Azilsartan treatment significantly improved kidney function, reduced tissue damage, and modulated inflammatory and apoptotic markers.
• Azilsartan suppressed oxidative stress, downregulated pro-inflammatory genes, and inhibited the HMGB1/NF-κB/p38/ERK1/2/JNK signaling pathway.

Conclusions:

• Azilsartan exhibits significant nephroprotective activity against renal IR injury in rats.
• Its protective effects are attributed to antioxidant, anti-inflammatory, and anti-apoptotic properties.
• Azilsartan effectively inhibits the HMGB1/NF-κB/p38/ERK1/2/JNK signaling pathway, offering a potential therapeutic strategy for renal IR injury.