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

被引:24
作者
Alaaeldin, Rania [1 ]
Bakkar, Sally M. [2 ]
Mohyeldin, Reham H. [3 ]
Ali, Fares E. M. [4 ]
Abdel-Maqsoud, Nehad M. Reda [5 ]
Fathy, Moustafa [6 ,7 ]
机构
[1] Deraya Univ, Fac Pharm, Dept Biochem, Al Minya 61519, Egypt
[2] Assiut Univ, Fac Med, Dept Biochem, Assiut 71515, Egypt
[3] Deraya Univ, Fac Pharm, Dept Pharmacol & Toxicol, Al Minya 61519, Egypt
[4] Al Azhar Univ, Fac Pharm, Dept Pharmacol & Toxicol, Assiut Branch, Assiut 71524, Egypt
[5] Deraya Univ, Fac Med, Dept Pathol, Al Minya 61519, Egypt
[6] Minia Univ, Fac Pharm, Dept Biochem, Al Minya 61511, Egypt
[7] Univ Toyama, Grad Sch Med & Pharmaceut Sci, Dept Regenerat Med, Toyama 9300194, Japan
关键词
azilsartan; renal ischemia; reperfusion injury; NF-kappa B; ERK1; 2; JNK; apoptosis; CELL-CYCLE ARREST; IN-VIVO; ISCHEMIA/REPERFUSION INJURY; HEPATOCELLULAR-CARCINOMA; SIGNALING PATHWAYS; ACTIVATION; KIDNEY; DIFFERENTIATION; PROLIFERATION; INFLAMMATION;
D O I
10.3390/cells12010185
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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-kappa B, and p53 proteins were investigated using ELISA. mRNA levels of IL-1 beta,IL6, IL10, TNF-alpha, NF-kappa B, p53, and bax 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-kappa B, and p53 levels, decreasing GPX and SOD activities, and up-regulation of NF-kappa B, IL-1 beta,IL6, TNF-alpha, p53, and bax genes. Furthermore, it up-regulated the expression of phosphorylated/total ratio of p38, ERK1/2, and JNK proteins. Interestingly, treat-ment 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-kappa B, and p53 levels, elevated GPX and SOD activities, down-regulated the expression of NF-kappa B, IL-1 beta,IL6, TNF-alpha, p53, and bax genes, and up-regulated IL10 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-kappa B/p38/ERK1/2/JNK signaling pathway.
引用
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页数:15
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