scholarly journals Nephroprotective Effects of Polydatin against Ischemia/Reperfusion Injury: A Role for the PI3K/Akt Signal Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Hong-Bao Liu ◽  
Qiu-Hong Meng ◽  
Chen Huang ◽  
Jian-Bo Wang ◽  
Xiao-Wei Liu
Keyword(s):  
Nitric Oxide ◽  
Molecular Mechanisms ◽  
Glutathione Transferase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Interleukin 1 ◽  
Specific Inhibitor ◽  
Prostaglandin E ◽  
Beneficial Effects

Oxidative stress and inflammation are involved in the pathogenesis in renal ischemia/reperfusion (I/R) injury. It has been demonstrated that polydatin processed the antioxidative, anti-inflammatory, and nephroprotective properties. However, whether it has beneficial effects and the possible mechanisms on renal I/R injury remain unclear. In our present study I/R models were simulated bothin vitroandin vivo. Compared with vehicle control, the administration of polydatin significantly improved the renal function, accelerated the mitogenic response and reduced cell apoptosis in renal I/R injury models, strongly suppressed the I/R-induced upregulation of the expression of tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, inducible nitric oxide synthase, prostaglandin E-2, and nitric oxide levels, and dramatically decreased contents of malondialdehyde, but it increased the activity of superoxide dismutase, glutathione transferase, glutathione peroxidase and catalase, and the level of glutathione. Further investigation showed that polydatin upregulated the phosphorylation of Akt in kidneys of I/R injury dose-dependently. However, all beneficial effects of polydatin mentioned above were counteracted when we inhibited PI3K/Akt pathway with its specific inhibitor, wortmannin. Taken together, the present findings provide the first evidence demonstrating that PD exhibited prominent nephroprotective effects against renal I/R injury by antioxidative stress and inflammation through PI3-K/Akt-dependent molecular mechanisms.

scholarly journals Normothermic Ex-vivo Kidney Perfusion in a Porcine Auto-Transplantation Model Preserves the Expression of Key Mitochondrial Proteins: An Unbiased Proteomics Analysis

2020 ◽  
Author(s):  
Caitriona M. McEvoy ◽  
Sergi Clotet-Freixas ◽  
Tomas Tokar ◽  
Chiara Pastrello ◽  
Shelby Reid ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Kidney Injury ◽  
Tca Cycle ◽  
Proteomics Analysis ◽  
Beneficial Effects ◽  
Kidney Perfusion

AbstractNormothermic ex-vivo kidney perfusion (NEVKP) results in significantly improved graft function in porcine auto-transplant models of DCD injury compared to static cold storage (SCS); however, the molecular mechanisms underlying these beneficial effects remain unclear. We performed an unbiased proteomics analysis of 28 kidney biopsies obtained at 3 time points from pig kidneys subjected to 30-minutes of warm ischemia, followed by 8 hours of NEVKP or SCS, and auto-transplantation. 70/6593 proteins quantified were differentially expressed between NEVKP and SCS groups (FDR<0.05). Proteins increased in NEVKP mediated key metabolic processes including fatty acid ß-oxidation, the TCA-cycle and oxidative phosphorylation. Comparison of our findings with external datasets of ischemia-reperfusion, and other models of kidney injury confirmed that 47 of our proteins represent a common signature of kidney injury reversed or attenuated by NEVKP. We validated key metabolic proteins (ETFB, CPT2) by immunoblotting. Transcription factor databases identified PPARGC1A, PPARA/G/D and RXRA/B as the upstream regulators of our dataset, and we confirmed their increased expression in NEVKP with RT-PCR. The proteome-level changes observed in NEVKP mediate critical metabolic pathways that may explain the improved graft function observed. These effects may be coordinated by PPAR-family transcription factors, and may represent novel therapeutic targets in ischemia-reperfusion injury.

scholarly journals Huaier Extract Attenuates Acute Kidney Injury to Chronic Kidney Disease Transition by Inhibiting Endoplasmic Reticulum Stress and Apoptosis via miR-1271 Upregulation

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Jing-Ying Zhao ◽  
Yu-Bin Wu
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Endoplasmic Reticulum ◽  
Kidney Disease ◽  
Endoplasmic Reticulum Stress ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury

Endoplasmic reticulum stress (ERS) is strongly associated with acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Huaier extract (HE) protects against kidney injury; albeit, the underlying mechanism is unknown. We hypothesized that HE reduces kidney injury by inhibiting ERS. In this study, using an AKI-CKD mouse model of ischemia-reperfusion injury (IRI), we evaluated the effect of HE on AKI-CKD transition. We also explored the underlying molecular mechanisms in this animal model and in the HK-2 human kidney cell line. The results showed that HE treatment improved the renal function, demonstrated by a significant decrease in serum creatinine levels after IRI. HE appreciably reduced the degree of kidney injury and fibrosis and restored the expression of the microRNA miR-1271 after IRI. Furthermore, HE reduced the expression of ERS markers glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) and inhibited apoptosis in the IRI group. This in vivo effect was supported by in vitro results in which HE inhibited apoptosis and decreased the expression of CHOP and GRP78 induced by ERS. We demonstrated that CHOP is a target of miR-1271. In conclusion, HE reduces kidney injury, probably by inhibiting apoptosis and decreasing the expression of GRP78 and CHOP via miR-1271 upregulation.

scholarly journals Tadalafil significantly reduces ischemia reperfusion injury in skin island flaps

2013 ◽  
Vol 46 (01) ◽  
pp. 075-081 ◽  
Author(s):  
Oguz Kayiran ◽  
Suat S. Cuzdan ◽  
Afsin Uysal ◽  
Ugur Kocer
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Statistical Significance ◽  
Skin Flap ◽  
Smooth Muscles ◽  
Specific Inhibitor ◽  
Neutrophil Infiltration ◽  
Medication Group ◽  
Beneficial Effects ◽  
Ischemic Group

ABSTRACT Introduction: Numerous pharmacological agents have been used to enhance the viability of flaps. Ischemia reperfusion (I/R) injury is an unwanted, sometimes devastating complication in reconstructive microsurgery. Tadalafil, a specific inhibitor of phosphodiesterase type 5 is mainly used for erectile dysfunction, and acts on vascular smooth muscles, platelets and leukocytes. Herein, the protective and therapeutical effect of tadalafil in I/R injury in rat skin flap model is evaluated. Materials and Methods: Sixty epigastric island flaps were used to create I/R model in 60 Wistar rats (non-ischemic group, ischemic group, medication group). Biochemical markers including total nitrite, malondialdehyde (MDA) and myeloperoxidase (MPO) were analysed. Necrosis rates were calculated and histopathologic evaluation was carried out. Results: MDA, MPO and total nitrite values were found elevated in the ischemic group, however there was an evident drop in the medication group. Histological results revealed that early inflammatory findings (oedema, neutrophil infiltration, necrosis rate) were observed lower with tadalafil administration. Moreover, statistical significance (P < 0.05) was recorded. Conclusions: We conclude that tadalafil has beneficial effects on epigastric island flaps against I/R injury.

scholarly journals Antioxidant Activity and Cardioprotective Effect of a Nonalcoholic Extract ofVaccinium meridionaleSwartz during Ischemia-Reperfusion in Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Yasmin E. Lopera ◽  
Juliana Fantinelli ◽  
Luisa F. González Arbeláez ◽  
Benjamín Rojano ◽  
José Luis Ríos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reperfusion Injury ◽  
Cardiac Tissue ◽  
Ischemia Reperfusion ◽  
Antioxidant Properties ◽  
Thiobarbituric Acid ◽  
Scavenging Activity ◽  
Ischemia And Reperfusion Injury ◽  
Beneficial Effects

Our objective was to assess the antioxidant properties and the effects against the reperfusion injury of a nonalcoholic extract obtained by fermentation from the Colombian blueberry, mortiño (Vaccinium meridionaleSwartz, Ericaceae). Antioxidant properties were assessed byin vitrosystems. To examine the postischemic myocardial function, isolated rat hearts were treated 10 min before ischemia and during the first 10 min of reperfusion with the extract. To analyze the participation of nitric oxide (NO), other experiments were performed in the presence of nitric oxide synthase (NOS) inhibition withNG-nitro-L-arginine methyl ester (L-NAME). In cardiac tissue thiobarbituric acid reactive substances (TBARS) concentration, reduced glutathione (GSH) content, endothelial NOS (eNOS), and Akt expression were also measured. The blueberry extract showed higher total phenols and anthocyanins contents, scavenging activity of superoxide radical and systolic and diastolic function was improved, TBARS diminished, GSH was partially preserved, and both NOS and Akt expression increased in hearts treated with the extract. These beneficial effects were lost when eNOS was inhibited. In resume, these data show that the increase of eNOS expression via Akt and the scavenging activity contribute to the cardioprotection afforded by acute treatment with Colombian blueberry extract against ischemia and reperfusion injury.

scholarly journals Pyrogen–prostaglandin coupling in the pathogenesis of fever: evidence against a role for nitric oxide

1995 ◽  
Vol 73 (10) ◽  
pp. 1466-1474 ◽  
Author(s):  
Jane Redford ◽  
Isis Bishai ◽  
Flavio Coceani
Keyword(s):  
Nitric Oxide ◽  
Brain Tissue ◽  
Cyclic Gmp ◽  
Interleukin 1 ◽  
Prostaglandin E ◽  
Signal Transducer ◽  
Cerebral Tissue ◽  
Cerebral Microvessels

There is much debate on the mechanism by which blood-borne pyrogens trigger prostaglandin E2 (PGE2) synthesis in brain and fever. This investigation was undertaken to determine whether nitric oxide qualifies as a signal transducer for pyrogens at the interface between blood and brain. Experiments were carried out in vitro and in vivo using, respectively, preparations of cerebral tissue and microvessels from the rat, and the conscious, chronically instrumented cat. In vitro preparations produced PGE2 and its production increased during a 30-min treatment with interleukin 1 (brain tissue) or endotoxin (microvessels). In addition, both pyrogens increased cyclic GMP levels in cerebral microvessels. In both brain tissue and microvessels, NG-nitro-L-arginine had no effect on basal PGE2 release, while it curtailed the pyrogen-stimulated release. The same treatment reduced the cyclic GMP accumulation brought about by pyrogens in the microvessels. Conversely, in the conscious cat, inhibitors of nitric oxide synthesis (NG-monomethyl-L-argimne, NG-nitro-L-arginine) had no effect on fever and the concomitant elevation of PGE2 in cerebrospinal fluid, regardless of the pyrogen used (endotoxin, interleukin 1) and the route of administration (intravenous, intracerebroventricular). We conclude that nitric oxide may serve as a pyrogen mediator in brain. This mediator function, however, is seemingly not important in the development of fever.Key words: pyrogen, fever mechanism, nitric oxide, prostaglandin E2, blood–brain barrier.

Nitric oxide-induced regulation of renal organic cation transport after renal ischemia-reperfusion injury

2011 ◽  
Vol 301 (5) ◽  
pp. F997-F1004 ◽  
Author(s):  
R. Schneider ◽  
M. Meusel ◽  
B. Betz ◽  
M. Kersten ◽  
K. Möller-Ehrlich ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Organic Cation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Fractional Excretion ◽  
Renal Ischemia ◽  
Organic Cation Transporters ◽  
Cation Transporters

Renal organic cation transporters are downregulated by nitric oxide (NO) in rat endotoxemia. NO generated by inducible NO synthase (iNOS) is substantially increased in the renal cortex after renal ischemia-reperfusion (I/R) injury. Therefore, we investigated the effects of iNOS-specific NO inhibition on the expression of the organic cation transporters rOct1 and rOct2 (Slc22a1 and Slc22a2, respectively) after I/R injury both in vivo and in vitro. In vivo, N6-(1-iminoethyl)-l-lysine (l-NIL) completely inhibited NO generation after I/R injury. Moreover, l-NIL abolished the ischemia-induced downregulation of rOct1 and rOct2 as determined by qPCR and Western blotting. Functional evidence was obtained by measuring the fractional excretion (FE) of the endogenous organic cation serotonin. Concordant with the expression of the rate-limiting organic cation transporter, the FE of serotonin decreased after I/R injury and was totally abolished by l-NIL. In vitro, ischemia downregulated both rOct1 and rOct2, which were also abolished by l-NIL; the same was true for the uptake of the organic cation MPP. We showed that renal I/R injury downregulates rOct1 and rOct2, which is most probably mediated via NO. In principle, this may be an autocrine effect of proximal tubular epithelial cells. We conclude that rOct1, or rOct1 and rOct2 limit the rate of the renal excretion of serotonin.

Remifentanil Preconditioning Reduces Hepatic Ischemia–Reperfusion Injury in Rats via  Inducible Nitric Oxide Synthase Expression

2011 ◽  
Vol 114 (5) ◽  
pp. 1036-1047 ◽  
Author(s):  
Li-Qun Yang ◽  
Kun-Ming Tao ◽  
Yan-Tao Liu ◽  
Chi-Wai Cheung ◽  
Michael G. Irwin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion ◽  
Inducible Nos

Background Opioid preconditioning against ischemia reperfusion injury has been well studied in myocardial and neuronal tissues. The objective of this study was to determine whether remifentanil could attenuate hepatic injury and to investigate the mechanisms. Methods A rat model of hepatic ischemia reperfusion injury and a hepatocyte hypoxia reoxygenation (HR) injury model were used, respectively, in two series of experiments. Remifentanil was administered before ischemia or hypoxia and the experiments were repeated with previous administration of naloxone, L-arginine and N-ω-nitro-L-arginine methyl ester, a nonselective opioid receptor antagonist, a nitric oxide donor, and nitric oxide synthase (NOS) inhibitor, respectively. Serum aminotransferase, cytokines, and hepatic lipid peroxidation were measured. Histopathology examination and apoptotic cell detection were assessed. For the in vitro study, cell viability, intracellular nitric oxide, apoptosis, and NOS expression were evaluated. Results Remifentanil and L-arginine pretreatment reduced concentrations of serum aminotransferases and cytokines, decreased the concentrations of hepatic malondialdehyde and myeloperoxidase activity, and increased superoxide dismutase, nitric oxide, and inducible NOS expression in vivo. Decreased histologic damage and apoptosis were also seen in these two groups. These changes were prevented by previous administration of N-ω-nitro-L-arginine methyl ester but not naloxone. There was an increase in inducible NOS protein expression but not endogenous NOS in remifentanil and L-arginine pretreated groups compared with control, naloxone, and N-ω-nitro-L-arginine methyl ester groups. Conclusion Pretreatment with remifentanil can attenuate liver injury both in vivo and in vitro. Inducible NOS but not opioid receptors partly mediate this effect by exhausting reactive oxygen species and attenuating the inflammatory response.

scholarly journals Antibacterial and Anti-Inflammatory Activities ofPhysalis Alkekengivar.franchetiiand Its Main Constituents

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Zunpeng Shu ◽  
Na Xing ◽  
Qiuhong Wang ◽  
Xinli Li ◽  
Bingqing Xu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nuclear Translocation ◽  
Interleukin 1 ◽  
Inflammatory Activity ◽  
Prostaglandin E ◽  
Active Components ◽  
Necrosis Factor Alpha ◽  
Anti Inflammatory

This study was designed to determine whether the 50% EtOH fraction from AB-8 macroporous resin fractionation of a 70% EtOH extract ofP. Alkekengi(50-EFP) has antibacterial and/or anti-inflammatory activity bothin vivoandin vitroand to investigate the mechanism of 50-EFP anti-inflammatory activity. Additionally, this study sought to define the chemical composition of 50-EFP. Results indicated that 50-EFP showed significant antibacterial activityin vitroand efficacyin vivo. Moreover, 50-EFP significantly reduced nitric oxide (NO), prostaglandin E2(PGE2), tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1), and interleukin 6 (IL-6) production in lipopolysaccharide- (LPS-) stimulated THP-1 cells. Nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) (examined at the protein level) in THP-1 cells were suppressed by 50-EFP, which inhibited nuclear translocation of p65. Consistent with this anti-inflammatory activityin vitro, 50-EFP reduced inflammation in both animal models. Finally, seventeen compounds (8 physalins and 9 flavones) were isolated as major components of 50-EFP. Our data demonstrate that 50-EFP has antibacterial and anti-inflammatory activities bothin vitroandin vivo. The anti-inflammatory effect appears to occur, at least in part, through the inhibition of nuclear translocation of p65. Moreover, physalins and flavones are probably the active components in 50-EFP that exert antibacterial and anti-inflammatory activities.

scholarly journals Cynanchum wilfordii Polysaccharides Suppress Dextran Sulfate Sodium-Induced Acute Colitis in Mice and the Production of Inflammatory Mediators from Macrophages

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Chang-Won Cho ◽  
Sungeun Ahn ◽  
Tae-Gyu Lim ◽  
Hee-Do Hong ◽  
Young Kyoung Rhee ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Molecular Mechanisms ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Prostaglandin E ◽  
High Molecular Weight Fraction ◽  
Colon Tissue ◽  
Anti Inflammatory ◽  
Crude Polysaccharide

We recently reported the immune-enhancing effects of a high-molecular-weight fraction (HMF) of CW in macrophages and immunosuppressed mice, and this effect was attributed to a crude polysaccharide. As polysaccharides may also have anti-inflammatory functions, we investigated the anti-inflammatory effects and related molecular mechanisms of a crude polysaccharide (HMFO) obtained from HMF of CW in mice with dextran sulfate sodium- (DSS-) induced colitis and in lipopolysaccharide-induced RAW 264.7 macrophages. HMFO ameliorated the pathological characteristics of colitis and significantly reduced production of proinflammatory cytokines in the serum. Histological analysis indicated that HMFO improved the signs of histological damage such as abnormal crypts, crypt loss, and inflammatory cell infiltration induced by DSS. In addition, HMFO inhibited iNOS and COX-2 protein expression, as well as phosphorylated NF-κB p65 levels in the colon tissue of mice with DSS-induced colitis. In macrophages, HMFO inhibited several cytokines and enzymes involved in inflammation such as prostaglandin E2, nitric oxide, tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 by attenuating nuclear factor-κB (NF-κB) and mitogen-activated protein kinases. HMFO attenuated inflammation both in vitro and in vivo, primarily by inhibiting NF-κB activation. Our findings indicate that HMFO is a promising remedy for treating inflammatory bowel diseases, such as colitis.

scholarly journals p53 target Siva regulates apoptosis in ischemic kidneys

2011 ◽  
Vol 300 (5) ◽  
pp. F1130-F1141 ◽  
Author(s):  
Kurinji Singaravelu ◽  
Babu J. Padanilam
Keyword(s):  
Cytochrome C ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Tumor Necrosis Factor Receptor ◽  
Kidney Injury ◽  
Cytochrome C Release ◽  
Apoptosis Inhibition ◽  
Apoptosis Inducing Factor

The role of p53 in inducing apoptosis following acute kidney injury is well-established; however, the molecular mechanisms remain largely unknown. We report here that the p53 proapoptotic target Siva and its receptor CD27, a member of the tumor necrosis factor receptor family, are upregulated following renal ischemia-reperfusion injury (IRI). Inhibition of Siva using antisense oligonucleotides conferred functional and morphological protection, and it prevented apoptosis postrenal IRI in mice. Renal IRI in CD27-deficient mice displayed functional protection and partial inhibition of apoptosis, suggesting an incomplete role for CD27 in Siva-mediated apoptosis. To further elucidate mechanisms by which Siva elicits apoptosis, in vitro studies were performed. In Siva-transfected LLC-PK1 cells, Siva is persistently expressed in the nucleus at 3 h onwards and its translocation to mitochondria and the plasma membrane occurred at 6 h. Moreover, Siva overexpression induced mitochondrial permeability, cytochrome c release, caspase-8 and -9 activation, translocation of apoptosis-inducing factor (AIF) to the nucleus, and apoptosis. Inhibition of Siva in ischemic kidneys prevented mitochondrial release of cytochrome c and AIF. These data indicate that Siva function is pivotal in regulating apoptosis in the pathology of renal IRI. Targeting Siva may offer a potential therapeutic strategy for renal IRI.

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