title: 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: Division of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Division of Nephrology, Yibin Second People's Hospital, Yibin, China.
authors: D-Q
authors: DQ
authors: Xie
authors: Division of Nephrology, Yibin Second People's Hospital, Yibin, China.
authors: G-Y
authors: GY
authors: Sun
authors: Division of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors: X-G
authors: XG
authors: Zhang
authors: Division of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: 18280141016@163.com.
authors: H
authors: H
authors: Gan
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology*; D007249:Inflammation / Q000517:prevention & control; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D019194:Ischemic Preconditioning / Q000379:methods*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D003374:Coumarins; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D019869:Phosphatidylinositol 3-Kinases; C046627:osthol