Osthole Preconditioning Protects Rats Against Renal Ischemia-Reperfusion Injury

• Published in: Transplantation proceedings 2015-07, Vol.47 (6), p.1620-1626
• Main Authors: Xie, D.-Q, Sun, G.-Y, Zhang, X.-G, Gan, H
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - etiology; Acute Kidney Injury - prevention & control; Animals; Anti-Inflammatory Agents - pharmacology; Apoptosis - drug effects; Coumarins - pharmacology; Inflammation - prevention & control; Interleukin-6 - metabolism; Interleukin-8 - metabolism; Ischemic Preconditioning - methods; Kidney - blood supply; Kidney - drug effects; Male; NF-kappa B - metabolism; Oxidative Stress - drug effects; Phosphatidylinositol 3-Kinases - metabolism; Protective Agents - pharmacology; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury - prevention & control; Surgery; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2015.06.011

Abstract Background Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury. The pathogenetic mechanisms of renal I/R injury involve inflammation, oxidative stress, and apoptosis. Osthole, a natural coumarin derivative, has potential anti-inflammatory effects. This study investigated the effect of osthole on renal I/R injury and its potential mechanism. Methods We induced renal I/R injury by clamping the left renal artery for 45 min followed by reperfusion, along with a contralateral nephrectomy. We randomly assigned 30 rats to 3 groups (n = 10): sham-operated, vehicle-treated I/R, and osthole-treated I/R. We treated rats intra-peritoneally with osthole (40 mg/kg) or vehicle (40 mg/kg) 45 min before renal ischemia. We harvested serum and kidneys at 24 h after reperfusion. Renal function and histological changes were assessed. The expression of tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), and interleukin-6 (IL-6) in renal tissue and serum were examined by means of RT-PCR and ELISA, respectively. The expression of p-p85, p85, p-Akt, Akt, p-p65, and p65 were measured by means of Western blotting. Results Osthole pre-treatment significantly attenuated renal dysfunction, renal histological changes, NF-κB activation, and the expression of TNF-α, IL-8, and IL-6 induced by I/R injury, but the activation of PI3K/Akt signaling was further increased. Conclusions Osthole pre-treatment protects rats against renal I/R injury by suppressing NF-κB activation, which is involved in PI3K/Akt signaling activation. Thus, osthole may be a novel practical strategy to prevent renal I/R injury.