Nicorandil Protects against Ischaemia-Reperfusion Injury in Newborn Rat Kidney

Abstract

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 (K_ATP) 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 K_IR6.2 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 K_IR6.2 potentially through the PI3K-Akt-NF-κB axis.

Osthole Preconditioning Protects Rats Against Renal Ischemia-Reperfusion Injury

“…NF-kB is an important nuclear transcription factor that could induce the expression of various pro-inflammatory cytokines such as TNF-a and IL-6 and that consisted of p65, p50, p102, and p110. However, its activation is mainly dependent on p65 activation [7,8]. In our study, we found that both I/R insult and osthole have no influence on the expression of p65 but have influence on the expression of p-p65.…”

“…Therefore, suppression of NF-kB activation may be a promising intervention for the anti-inflammatory treatment in renal I/R injury [7].…”

Neuroprotective effect of nicorandil through inhibition of apoptosis by the PI3K/Akt1 pathway in a mouse model of deep hypothermic low flow

“…Numerous experimental and clinical studies have reported the protective effects of nicorandil in I/R injury, and have attributed these effects to its function as a K ATP channel opener [12,31,36]. Wang [31] showed that nicorandil exerted a protective effect on myocardial I/R injury by increasing the expression of Bcl-2 and decreasing the expression of Bax, changes that were mediated primarily by opening of the mitoK ATP channel and lowering of the Ca 2+ overload.…”

“…Wang [31] showed that nicorandil exerted a protective effect on myocardial I/R injury by increasing the expression of Bcl-2 and decreasing the expression of Bax, changes that were mediated primarily by opening of the mitoK ATP channel and lowering of the Ca 2+ overload. Moreover, Zhang [36] reported that nicorandil inhibited I/R-induced upregulation of caspase-3 and downregulation of Bcl-2 in I/R injury in kidney, an effect likely mediated by the PI3K/Akt signaling pathway. These studies, which were carried out in the heart and kidney, indicated that inhibition of apoptosis by opening of the mitoK ATP channel is one of the most important mechanisms by which nicorandil exerts its protective effects.…”

Different sulfonylureas induce the apoptosis of proximal tubular epithelial cell differently via closing KATP channel

“…This process may subsequently induce Ca 2+ -dependent-apoptosis (Efanova et al 1998). Several studies have shown that the opening of the K ATP channel is renoprotective (Shiraishi et al 2014; Assad et al 2009; Zhang et al 2013). So, SUs might have detrimental effects on kidney, which is a concern in clinical practice.…”