Osthole Preconditioning Protects Rats Against Renal Ischemia-Reperfusion Injury.

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.

• Authors: D-Q Xie, G-Y Sun, X-G Zhang, H Gan
• Journal: Transplantation proceedings (Transplant Proc) 2015 Jul-Aug Vol. 47 Issue 6 Pg. 1620-6 ISSN: 1873-2623 [Electronic] United States
• PMID: 26293024 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Coumarins
• Interleukin-6
• Interleukin-8
• NF-kappa B
• Protective Agents
• Tumor Necrosis Factor-alpha
• Phosphatidylinositol 3-Kinases
• osthol

Topics

• Acute Kidney Injury (etiology, 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, 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)
• Tumor Necrosis Factor-alpha (metabolism)