Combination of ACE inhibitor with nicorandil provides further protection in chronic kidney disease

Shiraishi, Takeshi; Tamura, Yoshifuru; Taniguchi, Koki; Higaki, Masato; Ueda, Shuko; Shima, Tomoko; Nagura, Michito; Nakagawa, Takahiko; Johnson, Richard J.; Uchida, Shunya

doi:10.1152/ajprenal.00521.2014

Cited by 20 publications

(27 citation statements)

References 36 publications

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Zhou

Shen

et al. 2018

Mol Med

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BackgroundSulfonylureas (SUs) are widely prescribed for the treatment of type 2 diabetes (T2DM). Sulfonylurea receptors (SURs) are their main functional receptors. These receptors are also found in kidney, especially the tubular cells. However, the effects of SUs on renal proximal tubular epithelial cells (PTECs) were unclear.MethodsThree commonly used SUs were included in this study to investigate if different SUs have different effects on the apoptosis of PTECs. HK-2 cells were exposed to SUs for 24 h prior to exposure to 30 mM glucose, the apoptosis rate was evaluated by Annexin/PI flow cytometry. Bcl-2, Bax and the ratio of LC3II to LC3I were also studied by western blot in vitro. Diazoxide was used to evaluate the role of KATP channel in SUs-induced apoptosis of PTECs. A Student’s t-test was used to assess significance for data within two groups.ResultsTreatment with glibenclamide aggravated the apoptosis of HK-2 cells in high-glucose, as indicated by a significant decrease in the expression of Bcl-2 and increase in Bax. Additionally, the decreased LC3II/LC3I reflects that the autophagy was inhibited by glibenclamide. Similar but less pronounced change was found in glimepiride group, however, nearly opposite effects were found in gliclazide group. Further, the effects of glibenclamide on apoptosis promotion and the decreased LC3II/LC3I were ameliorated obviously by treatment with 100uM diazoxide. The potential protection effect of gliclazide was also inhibited after opening the KATP channel.ConclusionOur results suggest that, the effects of glibenclamide and glimepiride on PTECs apoptosis, especially the former, were achieved in part by closing the KATP channel. In contrast to glibenclamide and glimepiride, therapeutic concentrations of gliclazide showed an inhibitory effect on apoptosis of PTECs, which may have a benefit in the preservation of functional PTECs mass.

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Section: Introductionmentioning

confidence: 99%

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

Zhang

Zhou

Shen

et al. 2018

Mol Med

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“…Sirt3 has also been demonstrated to protect against podocyte injury as the target of the membrane G protein-coupled receptor 5 (TGR5) in kidney injuries caused by obesity and diabetes mellitus [50]. In addition, Shiraishi et al [51] provided direct evidence that nicorandil may synergize with enalapril to alleviate chronic kidney injuries via regulation Sirt3. Our studies have highlighted the role of Sirt6 in podocytes, which has pleiotropic protective actions including anti-inflammatory and antiapoptotic effects, maintenance of the actin cytoskeleton, and promotion of autophagy [9].…”

Section: Nad + -Dependent Deacetylases On the Regulation Of Podocyte mentioning

confidence: 99%

Histone Deacetylases Take Center Stage on Regulation of Podocyte Function

et al. 2020

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Background: Podocytes (highly specialized and terminally differentiated epithelial cells) are integral components of the glomerular filtration barrier that are vulnerable to a variety of injuries and, as a result, they undergo a series of changes ranging from hypertrophy to detachment and apoptosis. Podocyte injury is a major determinant in proteinuric kidney disease and identification of potential therapeutic targets for preventing podocyte injury has clinical importance. Although numerous studies have achieved dramatic advances in the understanding of podocyte biology and its relevance to renal injury, few effective and specific therapies are available. Summary: Epigenetic modifications have been proven to play important roles in the pathogenesis of kidney diseases. Among them, histone deacetylase (HDAC)-mediated epigenetic acetylation in the kidney has attracted much attention, which may play multiple roles in both kidney development and the pathogenesis of kidney disease. Recent studies have demonstrated that HDAC protect against podocyte injury by regulation of inflammation, apoptosis, autophagy, mitochondrial function, and insulin resistance. In this review, we summarize recent advances in the understanding of the functions and regulatory mechanisms of HDAC in podocytes and associated proteinuric kidney diseases. In addition, we provide evidence of the potential therapeutic effects of HDAC inhibitors for proteinuric kidney disease. Key Messages: Pharmacological targeting of HDAC-mediated epigenetic processes may open new therapeutic avenues for chronic kidney disease.

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“…In addition, Tamura et al (2012) demonstrated the renoprotective effects of nicorandil on a rat remnant kidney model of chronic kidney disease. Moreover, Shiraishi et al (2014) demonstrated that nicorandil might synergize with renoprotective effects of enalapril in chronic kidney disease.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, nicorandil (K ATP channel opener) pretreatment caused upregulation of nrf2 in aortic tissues obtained from rats treated with high adenine diet at the level of mRNA suggesting improvement of oxidative stress in aortic tissues might reduce the aortic calcifications. The antioxidant action of nicorandil was demonstrated in a rat model of remnant kidney disease (Tamura et al 2012;Shiraishi et al 2014), rat model of renal I/R injury (Ozturk et al 2017) and brain injury after cardiac arrest in pigs (Zhu et al 2018). Endothelial dysfunctions in chronic kidney disease was demonstrated in high adenine rat model and occurred in the form of imbalance between the vasodilators (serum nitric oxide) and vasoconstrictors (serum endothelin) (Peng et al 2013;Ali et al 2015).…”

Section: Control Control Adeninementioning

confidence: 99%

Effects of nicorandil on vascular and renal dysfunctions in adenine-induced nephropathy: Possible underlying mechanisms

Hussein

El-Dosoky²,

Malek³

et al. 2019

gpb

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Vascular dysfunctions in chronic kidney disease (CKD) include endothelial dysfunctions and vascular calcification (VC). In the present study, we examined the possible protective effect of nicorandil (potassium channel opener) on renal and vascular dysfunctions in a rat model of adenine-induced nephropathy and its underlying mechanisms. Thirty-four male Sprague-Dawley rats were randomly allocated into 3 groups: Control group, Adenine group (animals received high-adenine diet for 4 weeks), and Nicorandil group (animals received adenine for 4 weeks and nicorandil 1 mg/kg per oral for 4 weeks). The results showed significant reduction in the body weight, heart rate (HR), hemoglobin contents, serum Ca 2+ and reduction in the expression of mRNA of endothelial nitric oxide synthase (eNOS) and nuclear factor erythroid related factor 2 (nrf2) genes in aortic tissues with significant increase in arterial blood pressure (ABP), serum creatinine, blood urea nitrogen (BUN), plasma renin activity (PRA), K + and phosphate (PO 4 3-), urinary albumin excretion (UAE) and aortic VC in Adenine group compared to normal group (p < 0.05). On the other hand, coadminsitration of nicorandil caused significant improvement in the studied parameters compared to Adenine group (p < 0.05). We concluded that nicorandil has a potential protective effect against the vascular and renal impairment induced by adenine, which might be due to attenuation of vascular calcifications, activation of Nrf2 and eNOS genes in aortic tissues.

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Combination of ACE inhibitor with nicorandil provides further protection in chronic kidney disease

Cited by 20 publications

References 36 publications

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

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

Histone Deacetylases Take Center Stage on Regulation of Podocyte Function

Effects of nicorandil on vascular and renal dysfunctions in adenine-induced nephropathy: Possible underlying mechanisms

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