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

• Published in: Cells (Basel, Switzerland) Switzerland), 2023-01, Vol.12 (1), p.185
• Main Authors: Alaaeldin, Rania, Bakkar, Sally M, Mohyeldin, Reham H, Ali, Fares E M, Abdel-Maqsoud, Nehad M Reda, Fathy, Moustafa
• Format: Article
• Language: English
• Subjects: Analysis; Angiotensin; Animals; Apoptosis; azilsartan; BAX protein; bcl-2-Associated X Protein - metabolism; Blood flow; Care and treatment; Caspase 3 - metabolism; Caspase-3; Cellulose; Chromosomal proteins; Complications and side effects; Creatinine; Creatinine - metabolism; ERK1/2; Experiments; Extracellular signal-regulated kinase; FDA approval; Gene expression; Health aspects; HMGB1 protein; HMGB1 Protein - metabolism; IL-1β; Interleukin 10; Interleukin-10 - metabolism; Interleukin-6 - metabolism; Ischemia; JNK; JNK protein; Kidney; Kidneys; Kinases; MAP Kinase Signaling System; NF-kappa B - metabolism; NF-κB; NF-κB protein; Oxidative stress; p53 Protein; Proteins; Rats; Renal function; renal ischemia/reperfusion injury; Reperfusion; Reperfusion Injury - metabolism; Signal Transduction; Superoxide Dismutase - metabolism; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumor proteins; Tumor Suppressor Protein p53 - metabolism; Western blotting
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells12010185

Renal ischemia/reperfusion (IR) injury is characterized by an unexpected impairment of blood flow to the kidney. Azilsartan is an angiotensin receptor blocker that is approved for the management of hypertension. The present study aimed to investigate, on molecular basics, the nephroprotective activity of azilsartan on renal IR injury in rats. Rats were assigned into four groups: (1) Sham group, (2) Azilsartan group, (3) IR group, and (4) IR/Azilsartan-treated group. Histological examination and renal function were evaluated. Levels of KIM-1, HMGB1, caspase 3, GPX, SOD, NF-κB, and p53 proteins were investigated using ELISA. mRNA levels of , , , , , , and were assessed by qRT-PCR. Expression of p38, JNK, and ERK1/2 proteins was investigated by Western blotting. IR injury resulted in tissue damage, elevation of creatinine, BUN, KIM-1, HMGB1, caspase 3, NF-κB, and p53 levels, decreasing GPX and SOD activities, and up-regulation of , , , , , genes. Furthermore, it up-regulated the expression of phosphorylated/total ratio of p38, ERK1/2, and JNK proteins. Interestingly, treatment of the injured rats with azilsartan significantly alleviated IR injury-induced histopathological and biochemical changes. It reduced the creatinine, BUN, KIM-1, HMGB1, caspase-3, NF-κB, and p53 levels, elevated GPX and SOD activities, down-regulated the expression of , , , , , genes, and up-regulated gene expression. Furthermore, it decreased the phosphorylated/total ratio of p38, ERK1/2, and JNK proteins. Azilsartan exhibited nephroprotective activity in IR-injured rats via its antioxidant effect, suppression of inflammation, attenuation of apoptosis, and inhibition of HMGB1/NF-κB/p38/ERK1/2/JNK signaling pathway.