Nicorandil protects against ischaemia-reperfusion injury in newborn rat kidney
| Autor: | Xia-Xia Zhao, Ai-Qi Zhang, Zhi-Liang Tian, Yu-Jing Zhang, Li Yao |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
Necrosis ATP-sensitive potassium channel Vasodilator Agents Apoptosis Pharmacology Proinflammatory cytokine Glibenclamide Phosphatidylinositol 3-Kinases KATP Channels Medicine Animals Potassium Channels Inwardly Rectifying Rats Wistar Nicorandil Inflammation Kidney urogenital system business.industry Acute kidney injury NF-kappa B Interleukin General Medicine Acute Kidney Injury medicine.disease Rats Disease Models Animal medicine.anatomical_structure Animals Newborn Anesthesia Reperfusion Injury cardiovascular system Cytokines medicine.symptom business Proto-Oncogene Proteins c-akt medicine.drug |
| Zdroj: | Pharmacology. 92(5-6) |
| ISSN: | 1423-0313 |
| Popis: | Ischaemia-reperfusion injury (IRI) is the predominant cause of acute kidney injury. Nevertheless, the underlying molecular mechanisms are still unclear. The current study investigated the effects of nicorandil on ATP-sensitive potassium (KATP) channels and the potential signal transduction pathway(s) in a rat kidney IRI model and in cultured tubular HK-2 cells subjected to oxygen and glucose deprivation/reoxygenation (OGD/R) injury. The standard procedure for IRI was performed in newborn rat kidneys. Pretreatment with nicorandil (10 mg/kg) 2 h prior to induction of IRI improved renal function, attenuated tubule damage, and prevented apoptosis of tubule cells, infiltration of neutrophils and macrophages, and production of inflammatory cytokines interleukin (IL)-6, IL-17 and tumour necrosis factor-a. Ischaemia-reperfusion-induced reduction of KIR6.2 was restored to normal levels by nicorandil. The activation of the phosphoinositide-3-kinase (PI3K)-Akt-nuclear factor (NF)-κB axis was detected in this rat kidney IRI model, which was blocked by nicorandil. The renoprotection of nicorandil against IRI was abolished by its inhibitor glibenclamide (1 mg/kg). Similar results were obtained in OGD/R-damaged HK-2 cells. Taken together, our findings demonstrated the specific renoprotective role of nicorandil in the newborn rat IRI kidney by decreasing the production of inflammatory cytokines, and restoring the expression of KIR6.2 potentially through the PI3K-Akt-NF-κB axis. |
| Databáze: | OpenAIRE |
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