Protective effects of octreotide on renal ischemia-reperfusion injury
Zhen Xu, Peng Han, Zhiqiang Qin, Jingyuan Tang, Wei Wang
Abstract
Zhen Xu, Peng Han, Zhiqiang Qin, Jingyuan Tang, Wei Wang
Abstract
Objective To investigate the protective effects of octreotide (OCT) on renal ischemia-reperfusion (I/R) injury and its underlying mechanism. Methods Mice were randomly divided into three groups (n=8) using randomized number table method: Sham group, I/R group and octreotide preconditioning (OPC) + I/R group. Mice in group Sham received no treatment of I/R. The renal I/R was established in group I/R and group OPC+ I/R. Serum and renal tissues from these mice were collected 24 h after I/R. The levels of serum creatinine (SCr) and blood urea nitrogen (BUN) were measured. The renal injury was observed by hematoxylin-eosin (HE) staining. The contents of renal malondialdehyde (MDA)and the activities of superoxide dismutase(SOD)were tested. The levels of nuclear factor erythroid 2-related factor 2(Nrf2), heme oxygenase-1(HO-1) and nuclear factor-kappa B (NF-κB) expression in renal tissues were detected by Western blotting. Results The levels of SCr and BUN in I/R group [(113.38±18.39) μmol/L, (32.31±6.66)mmol/L] were significantly higher than in sham group [(27.61±7.77) μmol/L, (11.82±2.56) mmol/L; t=12.153, P=0.000; t=8.124, P=0.000]. The levels of SCr and BUN in OPC+ I/R group [(72.39±11.97) μmol/L, (22.12±3.75) mmol/L] were significantly lower compared to I/R group(t=5.285, P=0.000; t=3.774, P=0.003). Renal tubular injury scores in I/R group (4.13±0.84)were significantly higher than in OPC+ I/R group(2.13±0.64; t=5.736, P=0.000). The MDA levels in I/R group [(5.94±1.23) μmol/g ] were higher than in OPC+ I/R group [(3.92±0.69) μmol/g; t=5.004, P=0.002]. The SOD activities in I/R group [(24.05±6.15) kU/g] were lower than in OPC+ I/R group [(34.64±6.77) kU/g; t=3.276, P=0.006]. The relative expressions of Nrf2 and HO-1 protein in OPC+ I/R group (4.60±0.88, 4.76±0.87) were significantly increased as compared with I/R group (2.35±0.50, 2.67±0.54; t=6.294, P=0.000; t=5.737, P=0.000). The relative expression of NF-κB protein in OPC + I/R group (2.51±0.21) was significantly decreased as compared with I/R group (5.02±0.75; t=7.434, P=0.000). Conclusion OCT protects renal against I/R injury, which may be through activation of Nrf2/HO-1 signaling pathway and downregulation of NF-κB expression. Key words: Octreotide; Renal ischemia; Reperfusion injury; Nuclear factor erythroid 2-related factor 2; Nuclear factor-kappa B
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Objective To investigate the protective effects of octreotide (OCT) on renal ischemia-reperfusion (I/R) injury and its underlying mechanism. Methods Mice were randomly divided into three groups (n=8) using randomized number table method: Sham group, I/R group and octreotide preconditioning (OPC) + I/R group. Mice in group Sham received no treatment of I/R. The renal I/R was established in group I/R and group OPC+ I/R. Serum and renal tissues from these mice were collected 24 h after I/R. The levels of serum creatinine (SCr) and blood urea nitrogen (BUN) were measured. The renal injury was observed by hematoxylin-eosin (HE) staining. The contents of renal malondialdehyde (MDA)and the activities of superoxide dismutase(SOD)were tested. The levels of nuclear factor erythroid 2-related factor 2(Nrf2), heme oxygenase-1(HO-1) and nuclear factor-kappa B (NF-κB) expression in renal tissues were detected by Western blotting. Results The levels of SCr and BUN in I/R group [(113.38±18.39) μmol/L, (32.31±6.66)mmol/L] were significantly higher than in sham group [(27.61±7.77) μmol/L, (11.82±2.56) mmol/L; t=12.153, P=0.000; t=8.124, P=0.000]. The levels of SCr and BUN in OPC+ I/R group [(72.39±11.97) μmol/L, (22.12±3.75) mmol/L] were significantly lower compared to I/R group(t=5.285, P=0.000; t=3.774, P=0.003). Renal tubular injury scores in I/R group (4.13±0.84)were significantly higher than in OPC+ I/R group(2.13±0.64; t=5.736, P=0.000). The MDA levels in I/R group [(5.94±1.23) μmol/g ] were higher than in OPC+ I/R group [(3.92±0.69) μmol/g; t=5.004, P=0.002]. The SOD activities in I/R group [(24.05±6.15) kU/g] were lower than in OPC+ I/R group [(34.64±6.77) kU/g; t=3.276, P=0.006]. The relative expressions of Nrf2 and HO-1 protein in OPC+ I/R group (4.60±0.88, 4.76±0.87) were significantly increased as compared with I/R group (2.35±0.50, 2.67±0.54; t=6.294, P=0.000; t=5.737, P=0.000). The relative expression of NF-κB protein in OPC + I/R group (2.51±0.21) was significantly decreased as compared with I/R group (5.02±0.75; t=7.434, P=0.000). Conclusion OCT protects renal against I/R injury, which may be through activation of Nrf2/HO-1 signaling pathway and downregulation of NF-κB expression. Key words: Octreotide; Renal ischemia; Reperfusion injury; Nuclear factor erythroid 2-related factor 2; Nuclear factor-kappa B
Key concepts: Blood urea nitrogen, Creatinine, Malondialdehyde, Kidney, Internal medicine, Endocrinology, Octreotide, Renal ischemia