Glucocorticoid receptor agonist dexamethasone attenuates renal ischemia/reperfusion injury by up-regulating eNOS/iNOS

Zhang, Jiong; Li, Junhua; Wang, Le; Han, Min; Xiao, Fang; Lan, Xiaoqin; Li, Yueqiang; Xu, Gang; Ying, Yao

doi:10.1007/s11596-014-1308-y

Cited by 17 publications

(7 citation statements)

References 23 publications

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“…In normal kidney tissues, endothelial NOS is predominantly expressed in the renal blood vessels and capillaries; neuronal NOS is predominantly expressed in the juxtaglomerular macula densa; and iNOS is expressed in the renal medullary thick ascending limb, proximal tubule, distal convoluted tubule and interlobular arteries, arcuate arteries and blood vessels, and other areas of the glomerulus (31). Under a pathophysiological state, iNOS exhibits high levels of expression in mesangial cells, epithelial cells, smooth muscle cells and renal tubular epithelial cells, and there are high levels of infiltrated inflammatory cells, including in the glomeruli and renal interstitium (32). The present study showed that honokiol significantly decreased the gene expression and activity of iNOS in the IRI rats.…”

Section: Discussionmentioning

confidence: 99%

Honokiol protects against renal ischemia/reperfusion injury via the suppression of oxidative stress, iNOS, inflammation and STAT3 in rats

et al. 2015

Molecular Medicine Reports

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Abstract. Honokiol is the predominant active ingredient in the commonly used traditional Chinese medicine, Magnolia, which has been confirmed in previous studies to exhibit anti-oxidation, antimicrobial, antitumor and other pharmacological effects. However, its effects on renal ischemia/reperfusion injury (IRI) remain to be elucidated. The present study aimed to examine the effects of honokiol on renal IRI, and to investigate its potential protective mechanisms in the heart. Male adult Wistar albino rats were induced into a renal IRI model. Subsequently, the levels of serum creatinine, blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), and the levels of serum nitrite and the kidney nitrite were examined in the IRI group. The levels of oxidative stress, inducible nitric oxide synthase (iNOS), inflammatory factors and caspase-3 were evaluated using a series of commercially available kits. The levels of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and the protein expression levels of STAT3 were determined using western blotting. Pretreatment with honokiol significantly reduced the levels of serum creatinine, BUN, ALT, AST and ALP, and the level of nitrite in the kidney of the IRI group, compared with the control group. The levels of malondialdehyde, the activity of myeloperoxidase, and the gene expression and activity of iNOS were reduced in the IRI rats, compared with the sham-operated rats, whereas the levels of superoxide dismutase and catalase were increased following treatment with honokiol in the IRI rats. In addition, the expression levels of tumor necrosis factor-α and interleukin-6 in the IRI rats were increased by honokiol. Treatment with honokiol suppressed the protein expression levels of p-STAT3 and caspase-3 in the IRI rats. These findings indicated that honokiol protects against renal IRI via the suppression of oxidative stress, iNOS, inflammation and STAT3 in the rat.

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Section: Discussionmentioning

confidence: 99%

Honokiol protects against renal ischemia/reperfusion injury via the suppression of oxidative stress, iNOS, inflammation and STAT3 in rats

et al. 2015

Molecular Medicine Reports

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“…In view of the above, attenuation of inflammation after acute ischemic kidney injury may be a suitable therapeutic strategy in the attenuation or prevention of progressive renal injury. Dexamethasone is a glucocorticoid, widely used in renal diseases as an anti-inflammatory and immunosuppressive agent [ 8 ]. Corticosteroids inhibit the synthesis of chemokines and cytokines resulting in protection against inflammation, and at high doses inhibit the immune response [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…It was already shown in experimental models that dexamethasone has a protective effect against ischemic damage in liver and hart [ 10 , 11 ]. In the kidney, pre-treatment with dexamethasone has been demonstrated to ameliorate the severity of an acute ischemic insult [ 8 ]. These studies, however, particularly covered the acute injury phase up to 24 h after the ischemic insult.…”

Section: Introductionmentioning

confidence: 99%

Short-term dexamethasone treatment transiently, but not permanently, attenuates fibrosis after acute-to-chronic kidney injury

et al. 2018

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BackgroundAcute kidney injury (AKI) is an underestimated, yet important, risk factor for the development of chronic kidney disease (CKD). Persistence of inflammation after a renal ischemic injury has been observed, both in experimental models and patients, and is thought to be an important mechanisms underlying progression of acute-to-chronic renal injury. Temporary suppression of inflammation immediately after AKI might therefore be a good first-line therapeutic strategy towards a better long term outcome.MethodsMale C57Bl/6 J mice (Charles River, 10–12 weeks of age) underwent warm (36 °C body temperature) unilateral ischemia-reperfusion of the kidney for 21 min, after which treatment with intraperitoneal injection of the corticosteroid dexamethasone (10 mg/kg) was initiated for 3 weeks. Both at that time point and after an additional 3 week post-treatment follow up period, fibrosis was quantified by collagen I gene expression and immunostaining, as well as gene expression analysis of fibrosis-related genes Tgfβ, Ccn2 (Ctgf), Pai-1 and Ccn3. Furthermore, inflammation was evaluated by Tnfα gene expression and protein expression of the F4/80 macrophage marker and the α-SMA fibroblast marker. Lastly, renal histopathology was quantified by a morphometric analysis of the tubulointerstitial area.ResultsTreatment with dexamethasone attenuated development of fibrosis, as evidenced by reduced collagen I gene expression and immunostaining, in combination with reduced gene expression of the pro-fibrotic Ccn2 and increased expression of the anti-fibrotic Ccn3. The effects of dexamethasone on renal fibrosis persisted during the 3 week follow up period, as evidenced by stagnation of collagen I deposition in the ischemic kidney, in contrast to vehicle-treatment, where progression of fibrosis was observed. However, expression levels of the pro-fibrotic genes re-approached those of vehicle-treated injured kidneys suggesting that the effects of dexamethasone on fibrosis beyond the treatment period are temporary.ConclusionA short term anti-inflammatory therapy with dexamethasone only transiently attenuates ischemia induced fibrosis. Prolonged or persistent anti-inflammatory treatment seems warranted to achieve long term benefit.Electronic supplementary materialThe online version of this article (10.1186/s12882-018-1151-7) contains supplementary material, which is available to authorized users.

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“…blood supply to an organ, in which the arterial blood supply shortens and led to a severe imbalance of metabolic supply and demand that causes tissue hypoxia [2][3][4][5][6][7][8]; however, reperfusion is commonly used to re-establish reoxygenation and the restoration of blood flow, exacerbate renal tissue injury and dysfunction, and initiate profound inflammatory response [9]. The pathogenesis of AKI is complex; an excessive and inflammation response [10][11][12] has been elucidated as the key mechanisms of renal ischemia/ reperfusion injury.…”

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confidence: 99%

The Effect of Autophagy on Inflammation Cytokines in Renal Ischemia/Reperfusion Injury

et al. 2015

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Acute kidney injury (AKI) is characterized by a rapid loss of kidney function and an antigen-independent inflammatory process that causes tissue damage, which was one of the main manifestations of kidney ischemia/reperfusion (I/R). Recent studies have demonstrated autophagy participated in the pathological process of acute kidney injury. In this study, we discuss how autophagy regulated inflammation response in the kidney I/R. AKI was performed by renal I/R. Autophagy activator rapamycin (Rap) and inhibitor 3-methyladenine (MA) were used to investigate the role of autophagy on kidney function and inflammation response. After the experiment, kidney tissues were obtained for the detection of autophagy-related protein microtubule-associated protein light chain 3(LC3)II, Beclin1, and Rab7 and lysosome-associated membrane protein type (LAMP)2 protein by reverse transcription-polymerase chain reaction (PT-PCR) and Western blotting, and histopathology and tissue injury scores also. The blood was harvested to measure kidney function (creatinine (Cr) and blood urea nitrogen (BUN) levels) after I/R. Cytokines TNF-α, IL-6, HMGB1, and IL-10 were measured after I/R. I/R induced the expression of LC3II, Beclin1, LAMP2, and Rab7. The activation and inhibition of autophagy by rapamycin and 3-MA were promoted and attenuated histological and renal function in renal I/R rats, respectively. Cytokines TNF-α, IL-6, and HMGB1 were decreased, and IL-10 was further increased after activation of autophagy treated in I/R rats, while 3-MA exacerbated the pro-inflammatory cytokines TNF-α, IL-6, HMGB1, and anti-inflammatory cytokine IL-10 in renal I/R. I/R can activated the autophagy, and autophagy increase mitigated the renal injury by decreasing kidney injury score, levels of Cr and BUN after renal I/R, and inflammation response via regulating the balance of pro-inflammation and anti-inflammation cytokines.

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Glucocorticoid receptor agonist dexamethasone attenuates renal ischemia/reperfusion injury by up-regulating eNOS/iNOS

Cited by 17 publications

References 23 publications

Honokiol protects against renal ischemia/reperfusion injury via the suppression of oxidative stress, iNOS, inflammation and STAT3 in rats

Honokiol protects against renal ischemia/reperfusion injury via the suppression of oxidative stress, iNOS, inflammation and STAT3 in rats

Short-term dexamethasone treatment transiently, but not permanently, attenuates fibrosis after acute-to-chronic kidney injury

The Effect of Autophagy on Inflammation Cytokines in Renal Ischemia/Reperfusion Injury

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