Osthole decreases renal ischemia-reperfusion injury by suppressing JAK2/STAT3 signaling activation
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- Published online on: August 22, 2016 https://doi.org/10.3892/etm.2016.3603
- Pages: 2009-2014
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Copyright: © Luo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
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Abstract
Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury. The pathogenetic mechanisms underlying renal I/R injury involve inflammation, oxidative stress and apoptosis. Osthole is a coumarin derivative that exhibits potential anti‑inflammatory activity. The aim of the present study was to investigate the effect of osthole in renal I/R injury and its underlying mechanism. Renal I/R injury was induced by clamping the left renal artery for 45 min followed by 24 h reperfusion with the contralateral nephrectomy. A total of 70 rats were randomly assigned to seven groups (n=10 per group): Sham; IRI; and osthole (0, 5, 10, 20 and 40 mg/kg) groups. Rats were administered intraperitoneally with osthole 45 min prior to renal ischemia. Serum and renal tissue were harvested 24 h after reperfusion. Renal function and histological changes were assessed. In addition, the mRNA and protein expression of tumor necrosis factor‑α (TNF‑α), interleukin‑8 (IL‑8) and interleukin‑6 (IL‑6) in renal tissue and serum were evaluated using quantitative polymerase chain reaction and ELISA assays, respectively. The protein expression levels of p65, p‑p65, janus kinase 2 (JAK2), p‑JAK2, signal transducer and activator of transcription 3 (STAT3) and p‑STAT3 were measured using western blot analysis. The results indicate that osthole pretreatment was able to significantly attenuate the renal dysfunction in a dose‑dependent manner, histological changes and the expression of TNF‑α, IL‑8, IL‑6, p‑JAK2, p‑STAT3 and p‑p65 induced by renal I/R injury. However, neither osthole or I/R injury affected the expression p65, JAK2 and STAT3. Osthole pretreatment is able to reduce renal I/R injury by abrogating inflammation and the mechanism is partially involved in suppressing JAK2/STAT3 activation. Thus, osthole may be a novel practical strategy for the mitigation of renal I/R injury.
