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  1. Effects Of Ischemic Preconditioning On The Renal Ischemia- Reperfusion Injury

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    Anyamanesh S

    2003-07-01

    Full Text Available  During kidney and other organ transplantation, the organ to be transplanted, must inevitably remain out of the body with little or no blood perfusion at all for a long period of time (ischemia. These events have been suggested to cause the formation of oxygen- derived free radicals (OFR. Reperfusion (reintroduction of blood flow will further exacerbate the initial damage caused by the ischemic insult and may result in the production of free radicals. The aim of this study was to investigate whether induction of brief periods of renal artery occlusion (ischemic pre¬conditioning, IPC can provide protection from the effects of a subsequent period of ischemia and reperfusion (IR in the rat kidney."nMaterials and Methods: In this regard, 28 white, male rats were randomly and equally divided into four groups: Control (sham- operated, IPC alone, IR alone (30 min ischemia followed by 10 min reperfusion, and IPC- IR. Preconditioning involved the sequential clamping of the right renal artery for 5 min and declamping for 5 min for a total of 3 cycles. To demonstrate the effectiveness of IPC regimen, vitamin E as an endogenous antioxidant and an index of lipid peroxidation was measured by HPLC after its extraction from right renal venous plasma and right renal tissue."nResults: Results of this study showed that the amount of vitamin E of renal tissue and venous plasma in the IR group had a significant decrease when compared to the control group (P< 0.0001. Whereas the amount of this vitamin in both renal tissue and venous plasma of the IPC- IR group was significantly higher than that in the IR group (P< 0.0001, but did not show any significant difference with the control group."nConclusion: In this study, preconditioning method prevented the reduction of the endogenous antioxidant (Vit. E in encountering the following sustained ischemic insult. Therefore, we suggest that ischemic preconditioning can be used to protect the Vit. E level of kidney from its

  2. Ischemic conditioning by short periods of reperfusion attenuates renal ischemia/reperfusion induced apoptosis and autophagy in the rat

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    Chien Chiang-Ting

    2009-02-01

    Full Text Available Abstract Prolonged ischemia amplified iscehemia/reperfusion (IR induced renal apoptosis and autophagy. We hypothesize that ischemic conditioning (IC by a briefly intermittent reperfusion during a prolonged ischemic phase may ameliorate IR induced renal dysfunction. We evaluated the antioxidant/oxidant mechanism, autophagy and apoptosis in the uninephrectomized Wistar rats subjected to sham control, 4 stages of 15-min IC (I15 × 4, 2 stages of 30-min IC (I30 × 2, and total 60-min ischema (I60 in the kidney followed by 4 or 24 hours of reperfusion. By use of ATP assay, monitoring O2-. amounts, autophagy and apoptosis analysis of rat kidneys, I60 followed by 4 hours of reperfusion decreased renal ATP and enhanced reactive oxygen species (ROS level and proapoptotic and autophagic mechanisms, including enhanced Bax/Bcl-2 ratio, cytochrome C release, active caspase 3, poly-(ADP-ribose-polymerase (PARP degradation fragments, microtubule-associated protein light chain 3 (LC3 and Beclin-1 expression and subsequently tubular apoptosis and autophagy associated with elevated blood urea nitrogen and creatinine level. I30 × 2, not I15 × 4 decreased ROS production and cytochrome C release, increased Manganese superoxide dismutase (MnSOD, Copper-Zn superoxide dismutase (CuZnSOD and catalase expression and provided a more efficient protection than I60 against IR induced tubular apoptosis and autophagy and blood urea nitrogen and creatinine level. We conclude that 60-min renal ischemia enhanced renal tubular oxidative stress, proapoptosis and autophagy in the rat kidneys. Two stages of 30-min ischemia with 3-min reperfusion significantly preserved renal ATP content, increased antioxidant defense mechanisms and decreased ischemia/reperfusion enhanced renal tubular oxidative stress, cytosolic cytochrome C release, proapoptosis and autophagy in rat kidneys.

  3. Extracellular ascorbic acid fluctuation during the protective process of ischemic preconditioning in rabbit renal ischemia-reperfusion model measured

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    LIU Lei; LIN Yu-qing; YAN Long-tao; HONG Kai; HOU Xiao-fei; MAO Lan-qun; MA Lu-lin

    2010-01-01

    Background Ascorbic acid has important antioxidant properties, and may play a role in the protective effects of ischemic preconditioning on later ischemia-reperfusion. Herein, we examined the role of endogenous extracellular ascorbic acid in ischemic preconditioning in the kidney.Methods We developed a solitary rabbit kidney model where animals received ischemia-reperfusion only (ischemia-reperfusion group, n=15) or ischemic preconditioning followed by ischemia-reperfusion (ischemic preconditioning group, n=15). Ischemia-reperfusion was induced by occluding and loosening of the renal pedicle. The process of ischemic preconditioning included 15-minute brief ischemia and 10-minute reperfusion. In vivo microdialysis coupled with online electrochemical detection was used to determine levels of endogenous extracellular ascorbic acid in both groups. The extent of tissue damage was determined in kidney sections stained with hematoxylin and eosin. Serum creatinine and urea nitrogen were also detected to assess renal function.Results During ischemia-reperfusion, the extracellular ascorbic acid concentration during ischemia increased rapidly to the peak level ((130.01 ±9.98)%), and then decreased slowly to near basal levels. Similar changes were observed during reperfusion (peak level, (126.78±18.24)%). In the ischemic preconditioning group there was a similar pattern of extracellular ascorbic acid concentration during ischemic preconditioning. However, the ascorbic acid level was significantly lower during the ischemia and early reperfusion stage compared to the ischemia-reperfusion group. Additionally, the extent of glomerular ischemic collapse, tubular dilation, tubular denudation, and loss of brush border were markedly attenuated in the ischemic preconditioning group. Levels of serum creatinine and urea nitrogen were also decreased significantly in the ischemic preconditioning group.Conclusions Ischemic preconditioning may protect renal tissue against ischemia-reperfusion

  4. Diannexin protects against renal ischemia reperfusion injury and targets phosphatidylserines in ischemic tissue.

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    Kimberley E Wever

    Full Text Available Renal ischemia/reperfusion injury (IRI frequently complicates shock, renal transplantation and cardiac and aortic surgery, and has prognostic significance. The translocation of phosphatidylserines to cell surfaces is an important pro-inflammatory signal for cell-stress after IRI. We hypothesized that shielding of exposed phosphatidylserines by the annexin A5 (ANXA5 homodimer Diannexin protects against renal IRI. Protective effects of Diannexin on the kidney were studied in a mouse model of mild renal IRI. Diannexin treatment before renal IRI decreased proximal tubule damage and leukocyte influx, decreased transcription and expression of renal injury markers Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 and improved renal function. A mouse model of ischemic hind limb exercise was used to assess Diannexin biodistribution and targeting. When comparing its biodistribution and elimination to ANXA5, Diannexin was found to have a distinct distribution pattern and longer blood half-life. Diannexin targeted specifically to the ischemic muscle and its affinity exceeded that of ANXA5. Targeting of both proteins was inhibited by pre-treatment with unlabeled ANXA5, suggesting that Diannexin targets specifically to ischemic tissues via phosphatidylserine-binding. This study emphasizes the importance of phosphatidylserine translocation in the pathophysiology of IRI. We show for the first time that Diannexin protects against renal IRI, making it a promising therapeutic tool to prevent IRI in a clinical setting. Our results indicate that Diannexin is a potential new imaging agent for the study of phosphatidylserine-exposing organs in vivo.

  5. Effects of dexmedetomidine in conjunction with remote ischemic preconditioning on renal ischemia–reperfusion injury in rats

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    Emine Bagcik

    2014-12-01

    Full Text Available Background and objectives: The aim of this study was to evaluate the effects of remote ischemic preconditioning by brief ischemia of unilateral hind limb when combined with dexmedetomidine on renal ischemia-reperfusion injury by histopathology and active caspase-3 immunoreactivity in rats. Methods: 28 Wistar albino male rats were divided into 4 groups. Group I (Sham, n = 7: Laparotomy and renal pedicle dissection were performed at 65th minute of anesthesia and the rats were observed under anesthesia for 130min. Group II (ischemia-reperfusion, n = 7: At 65th minute of anesthesia bilateral renal pedicles were clamped. After 60 min ischemia 24 h of reperfusion was performed. Group III (ischemia-reperfusion + dexmedetomidine, n = 7: At the fifth minute of reperfusion (100 μg/kg intra-peritoneal dexmedetomidine was administered with ischemia-reperfusion group. Reperfusion lasted 24 h. Group IV (ischemia-reperfusion + remote ischemic preconditioning + dexmedetomidine, n = 7: After laparotomy, three cycles of ischemic preconditioning (10 min ischemia and 10 min reperfusion were applied to the left hind limb and after 5 min with group III. Results: Histopathological injury scores and active caspase-3 immunoreactivity were significantly lower in the Sham group compared to the other groups. Histopathological injury scores in groups III and IV were significantly lower than group II (p = 0.03 and p = 0.05. Active caspase-3 immunoreactivity was significantly lower in the group IV than group II (p = 0.01 and there was no significant difference between group II and group III (p = 0.06. Conclusions: Pharmacologic conditioning with dexmedetomidine and remote ischemic preconditioning when combined with dexmedetomidine significantly decreases renal ischemia- reperfusion injury histomorphologically. Combined use of two methods prevents apoptosis via active caspase-3.

  6. Acute hepatic ischemic-reperfusion injury induces a renal cortical "stress response," renal "cytoresistance," and an endotoxin hyperresponsive state.

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    Zager, Richard A; Johnson, Ali C M; Frostad, Kirsten B

    2014-10-01

    Hepatic ischemic-reperfusion injury (HIRI) is considered a risk factor for clinical acute kidney injury (AKI). However, HIRI's impact on renal tubular cell homeostasis and subsequent injury responses remain ill-defined. To explore this issue, 30-45 min of partial HIRI was induced in CD-1 mice. Sham-operated or normal mice served as controls. Renal changes and superimposed injury responses (glycerol-induced AKI; endotoxemia) were assessed 2-18 h later. HIRI induced mild azotemia (blood urea nitrogen ∼45 mg/dl) in the absence of renal histologic injury or proteinuria, implying a "prerenal" state. However, marked renal cortical, and isolated proximal tubule, cytoprotective "stress protein" gene induction (neutrophil gelatinase-associated lipocalin, heme oxygenase-1, hemopexin, hepcidin), and increased Toll-like receptor 4 (TLR4) expression resulted (protein/mRNA levels). Ischemia caused release of hepatic heme-based proteins (e.g., cytochrome c) into the circulation. This corresponded with renal cortical oxidant stress (malondialdehyde increases). That hepatic derived factors can evoke redox-sensitive "stress protein" induction was implied by the following: peritoneal dialysate from HIRI mice, soluble hepatic extract, or exogenous cytochrome c each induced the above stress protein(s) either in vivo or in cultured tubule cells. Functional significance of HIRI-induced renal "preconditioning" was indicated by the following: 1) HIRI conferred virtually complete morphologic protection against glycerol-induced AKI (in the absence of hyperbilirubinemia) and 2) HIRI-induced TLR4 upregulation led to a renal endotoxin hyperresponsive state (excess TNF-α/MCP-1 gene induction). In conclusion, HIRI can evoke "renal preconditioning," likely due, in part, to hepatic release of pro-oxidant factors (e.g., cytochrome c) into the systemic circulation. The resulting renal changes can impact subsequent AKI susceptibility and TLR4 pathway-mediated stress.

  7. Renoprotective Mechanism of Remote Ischemic Preconditioning Based on Transcriptomic Analysis in a Porcine Renal Ischemia Reperfusion Injury Model.

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    Young Eun Yoon

    Full Text Available Ischemic preconditioning (IPC is a well-known phenomenon in which tissues are exposed to a brief period of ischemia prior to a longer ischemic event. This technique produces tissue tolerance to ischemia reperfusion injury (IRI. Currently, IPC's mechanism of action is poorly understood. Using a porcine single kidney model, we performed remote IPC with renal IRI and evaluated the IPC mechanism of action. Following left nephrectomy, 15 female Yorkshire pigs were divided into three groups: no IPC and 90 minutes of warm ischemia (control, remote IPC immediately followed by 90 minutes of warm ischemia (rIPCe, and remote IPC with 90 minutes of warm ischemia performed 24 hours later (rIPCl. Differential gene expression analysis was performed using a porcine-specific microarray. The microarray analysis of porcine renal tissues identified 1,053 differentially expressed probes in preconditioned pigs. Among these, 179 genes had altered expression in both the rIPCe and rIPCl groups. The genes were largely related to oxidation reduction, apoptosis, and inflammatory response. In the rIPCl group, an additional 848 genes had altered expression levels. These genes were primarily related to immune response and inflammation, including those coding for cytokines and cytokine receptors and those that play roles in the complement system and coagulation cascade. In the complement system, the membrane attack complex was determined to be sublytic, because it colocalized with phosphorylated extracellular signal-regulated kinase. Furthermore, alpha 2 macroglobulin, tissue plasminogen activator, uterine plasmin trypsin inhibitor, and arginase-1 mRNA levels were elevated in the rIPCl group. These findings indicate that remote IPC produces renoprotective effects through multiple mechanisms, and these effects develop over a long timeframe rather than immediately following IPC.

  8. Molecular Mechanisms of Renal Ischemic Conditioning Strategies

    NARCIS (Netherlands)

    Kierulf-Lassen, Casper; Nieuwenhuijs-Moeke, Gertrude J.; Krogstrup, Nicoline V.; Oltean, Mihai; Jespersen, Bente; Dor, Frank J. M. F.

    2015-01-01

    Ischemia-reperfusion injury is the leading cause of acute kidney injury in a variety of clinical settings such as renal transplantation and hypovolemic and/or septic shock. Strategies to reduce ischemia-reperfusion injury are obviously clinically relevant. Ischemic conditioning is an inherent part o

  9. Preclinical Evidence for the Efficacy of Ischemic Postconditioning against Renal Ischemia-Reperfusion Injury, a Systematic Review and Meta-Analysis

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    Jonker, Simone J.; Menting, Theo P.; Warlé, Michiel C.; Ritskes-Hoitinga, Merel; Wever, Kimberley E.

    2016-01-01

    Background Renal ischemia-reperfusion injury (IRI) is a major cause of kidney damage after e.g. renal surgery and transplantation. Ischemic postconditioning (IPoC) is a promising treatment strategy for renal IRI, but early clinical trials have not yet replicated the promising results found in animal studies. Method We present a systematic review, quality assessment and meta-analysis of the preclinical evidence for renal IPoC, and identify factors which modify its efficacy. Results We identified 39 publications studying >250 control animals undergoing renal IRI only and >290 animals undergoing renal IRI and IPoC. Healthy, male rats undergoing warm ischemia were used in the vast majority of studies. Four studies applied remote IPoC, all others used local IPoC. Meta-analysis showed that both local and remote IPoC ameliorated renal damage after IRI for the outcome measures serum creatinine, blood urea nitrogen and renal histology. Subgroup analysis indicated that IPoC efficacy increased with the duration of index ischemia. Measures to reduce bias were insufficiently reported. Conclusion High efficacy of IPoC is observed in animal models, but factors pertaining to the internal and external validity of these studies may hamper the translation of IPoC to the clinical setting. The external validity of future animal studies should be increased by including females, comorbid animals, and transplantation models, in order to better inform clinical trial design. The severity of renal damage should be taken into account in the design and analysis of future clinical trials. PMID:26963819

  10. Preclinical Evidence for the Efficacy of Ischemic Postconditioning against Renal Ischemia-Reperfusion Injury, a Systematic Review and Meta-Analysis.

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    Simone J Jonker

    Full Text Available Renal ischemia-reperfusion injury (IRI is a major cause of kidney damage after e.g. renal surgery and transplantation. Ischemic postconditioning (IPoC is a promising treatment strategy for renal IRI, but early clinical trials have not yet replicated the promising results found in animal studies.We present a systematic review, quality assessment and meta-analysis of the preclinical evidence for renal IPoC, and identify factors which modify its efficacy.We identified 39 publications studying >250 control animals undergoing renal IRI only and >290 animals undergoing renal IRI and IPoC. Healthy, male rats undergoing warm ischemia were used in the vast majority of studies. Four studies applied remote IPoC, all others used local IPoC. Meta-analysis showed that both local and remote IPoC ameliorated renal damage after IRI for the outcome measures serum creatinine, blood urea nitrogen and renal histology. Subgroup analysis indicated that IPoC efficacy increased with the duration of index ischemia. Measures to reduce bias were insufficiently reported.High efficacy of IPoC is observed in animal models, but factors pertaining to the internal and external validity of these studies may hamper the translation of IPoC to the clinical setting. The external validity of future animal studies should be increased by including females, comorbid animals, and transplantation models, in order to better inform clinical trial design. The severity of renal damage should be taken into account in the design and analysis of future clinical trials.

  11. Moxonidine prevents ischemia/reperfusion-induced renal injury in rats.

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    Tsutsui, Hidenobu; Sugiura, Takahiro; Hayashi, Kentaro; Ohkita, Mamoru; Takaoka, Masanori; Yukimura, Tokihito; Matsumura, Yasuo

    2009-01-28

    Enhancement of renal sympathetic nerve activity during renal ischemia and its consequent effect on norepinephrine overflow from nerve endings after reperfusion play important roles in the development of ischemic acute kidney injury. In the present study, we evaluated whether moxonidine, an alpha(2)-adrenaline/I(1)-imidazoline receptor agonist which is known to elicit sympathoinhibitory action, would prevent the post-ischemic renal injury. Ischemic acute kidney injury was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Intravenous (i.v.) injection of moxonidine at a dose of 360 nmol/kg to ischemic acute kidney injury rats suppressed the enhanced renal sympathetic nerve activity during the ischemic period, to a degree similar to findings with intracerebroventricular (i.c.v.) injection of moxonidine at a dose of 36 nmol/kg. On the other hand, suppressive effects of the i.v. treatment on renal venous norepinephrine overflow, renal dysfunction and tissue injury in the post-ischemic kidney were significantly greater than those elicited by the i.c.v. treatment. These results suggest that renoprotective effects of moxonidine on ischemic acute kidney injury probably result from its suppressive action on the ischemia-enhanced renal sympathetic nerve activity followed by norepinephrine spillover from the nerve endings of the post-ischemic kidney.

  12. Red propolis ameliorates ischemic-reperfusion acute kidney injury.

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    da Costa, Marcus Felipe Bezerra; Libório, Alexandre Braga; Teles, Flávio; Martins, Conceição da Silva; Soares, Pedro Marcos Gomes; Meneses, Gdayllon C; Rodrigues, Francisco Adelvane de Paulo; Leal, Luzia Kalyne Almeida Moreira; Miron, Diogo; Silva, Aline Holanda; Martins, Alice Maria Costa

    2015-08-15

    Acute kidney injury (AKI) remains a great problem in clinical practice. Renal ischemia/reperfusion (I/R) injury is a complex pathophysiological process. Propolis is a natural polyphenol-rich resinous substance collected by honeybees from a variety of plant sources that has anti-inflammatory and anti-oxidative properties. Red propolis (RP) protection in renal I/R injury was investigated. Male Wistar rats underwent unilateral nephrectomy and contralateral renal I/R (60 min). Rats were divided into four groups: (1) sham group, (2) RP group (sham-operated rats treated with RP), 3) IR group (rats submitted to ischemia) and (4) IR-RP (rats treated with RP before ischemia). At 48 h after reperfusion, renal function was assessed and kidneys were removed for analysis. I/R increased plasma levels of creatinine and reduced creatinine clearance (CrCl), and RP provided protection against this renal injury. Red propolis significantly improves oxidative stress parameters when compared with the IR group. Semiquantitative assessment of the histological lesions showed marked structural damage in I/R rats compared with the IR-RP rats. RP attenuates I/R-induced endothelial nitric oxide-synthase down regulation and increased heme-oxygenase expression in renal tissue. Red propolis protects kidney against acute ischemic renal failure and this protection is associated with reduced oxidative stress and eNOS and heme-oxygenase up regulation. Copyright © 2015 Elsevier GmbH. All rights reserved.

  13. Ischemic preconditioning protects post-ischemic renal function in anesthetized dogs: role of adenosine and adenine nucleotides

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    Fan-zhu LI; Shoji KIMURA; Akira NISHIYAMA; Matlubur RAHMAN; Guo-xing ZHANG; Youichi ABE

    2005-01-01

    Aim: To investigate the effects of renal ischemic preconditioning (IPC) on both renal hemodynamics and the renal interstitial concentrations of adenosine and adenine nucleotides induced by ischemia-reperfusion injury.Methods: Renal hemodynamics responses to ischemia-reperfusion injury in mongrel dog models were determined with or without multiple brief renal ischemic preconditioning treatments, as well as the adenosine A1 receptor antagonist (KW-3902),respectively.The renal interstitial concentrations of adenosine and adenine nucleotides in response to ischemia-reperfusion injury, either following 1-3 cycles of IPC or not, were measured simultaneously using microdialysis sampling technology.Results: One 10-min IPC, adenosine A1 receptor antagonist (KW3902) also shortened the recovery time of renal blood flow (RBF) and urine flow (UF), as well as mean blood pressure (BP).Advanced renal IPC attenuated the increment of adenosine and adenine nucleotides, as well as recovery time during the 60-min reperfusion which followed the 60-min renal ischemia.All of these recovery times were dependent on the cycles of 10-min IPC.The renal interstitial concentrations of adenosine and adenine nucleotides increased and decreased during renal ischemia and reperfusion, respectively.Conclusion: A significant relativity in dog models exists between the cycles of 10-min renal IPC and the recovery time of BP, UF, and RBF during the 60-min renal reperfusion following 60-min renal ischemia, respectively.Renal IPC can protect against ischemiareperfusion injury and the predominant effect of endogenous adenosine induced by prolonged renal ischemia; renal adenosine A1 receptor activation during the renal ischemia-reperfusion injury is detrimental to renal function.

  14. Ischemia reperfusion injury, ischemic conditioning and diabetes mellitus.

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    Lejay, Anne; Fang, Fei; John, Rohan; Van, Julie A D; Barr, Meredith; Thaveau, Fabien; Chakfe, Nabil; Geny, Bernard; Scholey, James W

    2016-02-01

    Ischemia/reperfusion, which is characterized by deficient oxygen supply and subsequent restoration of blood flow, can cause irreversible damages to tissue. Mechanisms contributing to the pathogenesis of ischemia reperfusion injury are complex, multifactorial and highly integrated. Extensive research has focused on increasing organ tolerance to ischemia reperfusion injury, especially through the use of ischemic conditioning strategies. Of morbidities that potentially compromise the protective mechanisms of the heart, diabetes mellitus appears primarily important to study. Diabetes mellitus increases myocardial susceptibility to ischemia reperfusion injury and also modifies myocardial responses to ischemic conditioning strategies by disruption of intracellular signaling responsible for enhancement of resistance to cell death. The purpose of this review is twofold: first, to summarize mechanisms underlying ischemia reperfusion injury and the signal transduction pathways underlying ischemic conditioning cardioprotection; and second, to focus on diabetes mellitus and mechanisms that may be responsible for the lack of effect of ischemic conditioning strategies in diabetes.

  15. Effect of U-74500A, a 21-aminosteroid on renal ischemia-reperfusion injury in rats.

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    Kaur, Hitchintan; Satyanarayana, Padi S V; Chopra, Kanwaljit

    2003-03-01

    Renal ischemia-reperfusion injury constitutes the most common pathogenic factor for acute renal failure and is the main contributor to renal dysfunction in allograft recipients and revascularization surgeries. Many studies have demonstrated that reactive oxygen species play an important role in ischemic acute renal failure. The aim of the present study was to investigate the effects of the synthetic antioxidant U-74500A, a 21-aminosteroid in a rat model of renal ischemia-reperfusion injury. Renal ischemia-reperfusion was induced by clamping unilateral renal artery for 45 min followed by 24 h of reperfusion. Two doses of U-74500A (4.0 mg/kg, i.v.) were administered 45 min prior to renal artery occlusion and then 15 min prior to reperfusion. Tissue lipid peroxidation was measured as thiobarbituric acid reacting substances (TBARS) in kidney homogenates. Renal function was assessed by estimating serum creatinine, blood urea nitrogen (BUN), creatinine and urea clearance. Renal morphological alterations were assessed by histopathological examination of hematoxylin-eosin stained sections of the kidneys. Ischemia-reperfusion produced elevated levels of TBARS and deteriorated the renal function as assessed by increased serum creatinine, BUN and decreased creatinine and urea clearance as compared to sham operated rats. The ischemic kidneys of rats showed severe hyaline casts, epithelial swelling, proteinaceous debris, tubular necrosis, medullary congestion and hemorrhage. U-74500A markedly attenuated elevated levels of TBARS as well as morphological changes, but did not improve renal dysfunction in rats subjected to renal ischemia-reperfusion. These results clearly demonstrate the in vivo antioxidant effect of U-74500A, a 21-aminosteroid in attenuating renal ischemia-reperfusion injury.

  16. Relation between reperfusion and hemorrhagic transformation in acute ischemic stroke

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    Horsch, Alexander D. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Rijnstate Hospital, Department of Radiology, Arnhem (Netherlands); Dankbaar, Jan Willem; Niesten, Joris M.; Seeters, Tom van; Schaaf, Irene C. van der; Velthuis, Birgitta K. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Graaf, Yolanda van der [Julius Center for Health Sciences and Primary Care, Utrecht (Netherlands); Kappelle, L.J. [University Medical Center, Department of Neurology, Utrecht Stroke Center, Utrecht (Netherlands); Collaboration: DUST investigators

    2015-12-15

    Intravenous recombinant tissue plasminogen activator (IV-rtPA) is given in acute ischemic stroke patients to achieve reperfusion. Hemorrhagic transformation (HT) is a serious complication of IV-rtPA treatment and related to blood-brain barrier (BBB) injury. It is unclear whether HT occurs secondary to reperfusion in combination with ischemic BBB injury or is caused by the negative effect of IV-rtPA on BBB integrity. The aim of this study was to establish the association between reperfusion and the occurrence of HT. From the DUST study, patients were selected with admission and follow-up non-contrast CT (NCCT) and CT perfusion (CTP) imaging, and a perfusion deficit in the middle cerebral artery territory on admission. Reperfusion was categorized qualitatively as reperfusion or no-reperfusion by visual comparison of admission and follow-up CTP. Occurrence of HT was assessed on follow-up NCCT. The association between reperfusion and occurrence of HT on follow-up was estimated by calculating odds ratios (ORs) and 95 % confidence intervals (CIs) with additional stratification for IV-rtPA treatment. Inclusion criteria were met in 299 patients. There was no significant association between reperfusion and HT (OR 1.2 95%CI 0.5-3.1). In patients treated with IV-rtPA (n = 203), the OR was 1.3 (95%CI 0.4-4.0), and in patients not treated with IV-rtPA (n = 96), the OR was 0.8 (95%CI 0.1-4.5). HT occurred in 14 % of the IV-rtPA patients and in 7 % of patients without IV-rtPA (95%CI of difference -1 to 14 %). Our results suggest that the increased risk of HT after acute ischemic stroke treatment is not dependent on the reperfusion status. (orig.)

  17. Influence of remote ischemic conditioning and tramadol hydrochloride on oxidative stress in kidney ischemia/reperfusion injury in rats

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    Oliveira,Rita de Cássia Silva de; BRITO, Marcus Vinicius Henriques; Ribeiro Júnior,Rubens Fernando Gonçalves; Oliveira,Leonam Oliver Durval; Monteiro,Andrew Moraes; Brandão,Fernando Mateus Viegas; Cavalcante,Lainy Carollyne da Costa; Gouveia,Eduardo Henrique Herbster; Henriques,Higor Yuri Bezerra

    2017-01-01

    Abstract Purpose: To evaluate the effects of tramadol hydrochloride associated to remote ischemic perconditioning on oxidative stress. Methods: Twenty five male rats (Wistar) underwent right nephrectomy and were distributed into five groups: Sham group (S); Ischemia/Reperfusion group (I/R) with 30 minutes of renal ischemia; Remote ischemic perconditioning group (Per) with three cycles of 10 minutes of I/R performed during kidney ischemia; Tramadol group (T) treated with tramadol hydrochlori...

  18. CURRENT REPERFUSION THERAPY POSSIBILITIES IN MYOCARDIAL INFARCTION AND ISCHEMIC STROKE

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    E. V. Konstantinova

    2015-01-01

    Full Text Available Myocardial infarction and ischemic stroke remain to be of the greatest medical and social importance because of their high prevalence, disability, and mortality rates. Intractable thrombotic occlusion of the respective artery leads to the formation of an ischemic lesion focus in the tissue of the heart or brain. Emergency reperfusion serves to decrease a necrotic focus, makes its formation reversible, and reduces patient death rates. The paper considers main reperfusion therapy lines: medical (with thrombolytic drugs and mechanical (with primary interventions one and their combination in treating patients with acute myocardial and cerebral ischemia. Each reperfusion procedure is discussed in view of its advantages, disadvantages, available guidelines, and possibilities of real clinical practice. Tenecteplase is assessed in terms of its efficacy, safety, and capacities for bolus administration, which allows its use at any hospital and at the pre-hospital stage. Prehospital thrombolysis permits reperfusion therapy to bring much closer to the patient and therefore aids in reducing time to reperfusion and in salvaging as much the myocardial volume as possible. The rapidest recovery of myocardial and cerebral perfusion results in a decreased necrotic area and both improved immediate and late prognosis. The results of randomized clinical trials studying the possibilities of the medical and mechanical methods to restore blood flow are analyzed in the context of evidence-based medicine. The reason why despite the available contraindications, limited efficiency, and the risk of hemorrhagic complications, thrombolytic therapy remains the method of choice for prehospital reperfusion, an alternative to primary percutaneous coronary intervention (PCI if it cannot be carried out in patients with myocardial infarction at the stated time, and the only treatment ischemic stroke treatment that has proven its efficiency and safety in clinical trials is under

  19. Sex differences in ischemia/reperfusion-induced acute kidney injury are dependent on the renal sympathetic nervous system.

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    Tanaka, Ryosuke; Tsutsui, Hidenobu; Ohkita, Mamoru; Takaoka, Masanori; Yukimura, Tokihito; Matsumura, Yasuo

    2013-08-15

    Resistance to ischemic acute kidney injury has been shown to be higher in female rats than in male rats. We found that renal venous norepinephrine overflow after reperfusion played important roles in the development of ischemic acute kidney injury. In the present study, we investigated whether sex differences in the pathogenesis of ischemic acute kidney injury were derived from the renal sympathetic nervous system using male and female Sprague-Dawley rats. Ischemia/reperfusion-induced acute kidney injury was achieved by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function was impaired after reperfusion in both male and female rats; however, renal dysfunction and histological damage were more severe in male rats than in female rats. Renal venous plasma norepinephrine levels after reperfusion were markedly elevated in male rats, but were not in female rats. These sex differences were eliminated by ovariectomy or treatment with tamoxifen, an estrogen receptor antagonist, in female rats. Furthermore, an intravenous injection of hexamethonium (25mg/kg), a ganglionic blocker, 5 min before ischemia suppressed the elevation in renal venous plasma norepinephrine levels after reperfusion, and attenuated renal dysfunction and histological damage in male rats, and ovariectomized and tamoxifen-treated female rats, but not in intact females. Thus, the present findings confirmed sex differences in the pathogenesis of ischemic acute kidney injury, and showed that the attenuation of ischemia/reperfusion-induced acute kidney injury observed in intact female rats may be dependent on depressing the renal sympathetic nervous system with endogenous estrogen.

  20. Specific features of reperfusion therapy for vertebrobasilar ischemic stroke

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    K. V. Anisimov

    2015-01-01

    Full Text Available Ischemic stroke in the vertebrobasilar system (VBS is characterized by the high rates of death and disability; reperfusion therapy in patients with a lesion focus in the VBS is safe and effective beyond the 4.5-hour therapeutic window. Actively developed current methods for the endovascular treatment of acute ischemic stroke enable one to increase recanalization rates and hence to improve the degree of functional recovery in this group of patients. Considering that there are no significant differences in the outcomes of systemic and selective thrombolytic therapy in patients with occlusion of the basilar arteries, the urgent problem is to increase the time from the onset of the disease to reperfusion therapy, therefore combined reperfusion therapy may be an optimal option. This approach would make it possible to initiate the therapy in a shorter period of time and to use the advantages of both reperfusion techniques. Intravenous thrombolysis as the rapidest and technically simplest method may be performed in the first step of therapy in the clinics unequipped with an X-ray surgical service, with the patient being further transported to a specialized endovascular center if the intravenous injection of a thrombolytic agent has no effect. Taking into account the fact that reperfusion therapy may be performed in patients with vertebrobasilar stroke in the wider therapeutic window, a similar organizational chart with multistep therapy for this disease might become the treatment of choice.

  1. Poly-IC preconditioning protects against cerebral and renal ischemia-reperfusion injury.

    Science.gov (United States)

    Packard, Amy E B; Hedges, Jason C; Bahjat, Frances R; Stevens, Susan L; Conlin, Michael J; Salazar, Andres M; Stenzel-Poore, Mary P

    2012-02-01

    Preconditioning induces ischemic tolerance, which confers robust protection against ischemic damage. We show marked protection with polyinosinic polycytidylic acid (poly-IC) preconditioning in three models of murine ischemia-reperfusion injury. Poly-IC preconditioning induced protection against ischemia modeled in vitro in brain cortical cells and in vivo in models of brain ischemia and renal ischemia. Further, unlike other Toll-like receptor (TLR) ligands, which generally induce significant inflammatory responses, poly-IC elicits only modest systemic inflammation. Results show that poly-IC is a new powerful prophylactic treatment that offers promise as a clinical therapeutic strategy to minimize damage in patient populations at risk of ischemic injury.

  2. Effects of ischemic preconditioning on cyclinD1 expression during early ischemic reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Fang-Gang Cai; Jian-Sheng Xiao; Qi-Fa Ye

    2006-01-01

    AIM: To observe the effect of ischemic preconditioning on cyclinD1 expression in rat liver cells during early ischemic reperfusion.METHODS: Fifty-four SD rats were randomly divided into ischemic preconditioning group (IP), ischemia/reperfusion group (IR) and sham operation group (SO). The IP and IR groups were further divided into four sub-groups (n = 6). Sham operation group (SO)served as the control group (n = 6). A model of partial liver ischemia/reperfusion was used, in which rats were subjected to liver ischemia for 60 min prior to reperfusion. The animals in the IP group underwent ischemic preconditioning twice for 5 min each time prior to the ischemia/reperfusion challenge. After 0, 1, 2, and 4 h of reperfusion, serum and liver tissue in each group were collected to detect the level of serum ALT, liver histopathology and expression of cyclinD1 mRNA and protein. Flow cytometry was used to detect cell cycle as the quantity indicator of cell regeneration.RESULTS: Compared with IR group, IP group showed asignificantly lower ALT level in 1 h to 4 h sub-groups (P< 0.05). Proliferation index(PI) indicated by the S-phase and G2/M-phase ratio [(S+G2/M)/(G0/G1+S+G2/M)] was significantly increased in IP group at 0 and 1 h (26.44± 7.60% vs 18.56 ± 6.40%,41.87 ± 7.27% vs 20.25 ±6.70%, P < 0.05). Meanwhile, cyclinD1 protein expression could be detected in IP group. But in IR group, cyclinD1 protein expression occurred 2 h after reperfusion. The expression of cyclinD1 mRNA increased significantly in IP group at 0 and 1 h (0.568 ± 0.112 vs 0.274 ± 0.069, 0.762± 0.164 vs 0.348 ± 0.093, P < 0.05).CONCLUSION: Ischemic preconditioning can protect liver cells against ischemia/reperfusion injury, which may be related to cell proliferation and expression of cyclinD1 during early ischemic reperfusion.

  3. TLR9 Mediates Remote Liver Injury following Severe Renal Ischemia Reperfusion.

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    Pieter J Bakker

    Full Text Available Ischemia reperfusion injury is a common cause of acute kidney injury and is characterized by tubular damage. Mitochondrial DNA is released upon severe tissue injury and can act as a damage-associated molecular pattern via the innate immune receptor TLR9. Here, we investigated the role of TLR9 in the context of moderate or severe renal ischemia reperfusion injury using wild-type C57BL/6 mice or TLR9KO mice. Moderate renal ischemia induced renal dysfunction but did not decrease animal well-being and was not regulated by TLR9. In contrast, severe renal ischemia decreased animal well-being and survival in wild-type mice after respectively one or five days of reperfusion. TLR9 deficiency improved animal well-being and survival. TLR9 deficiency did not reduce renal inflammation or tubular necrosis. Rather, severe renal ischemia induced hepatic injury as seen by increased plasma ALAT and ASAT levels and focal hepatic necrosis which was prevented by TLR9 deficiency and correlated with reduced circulating mitochondrial DNA levels and plasma LDH. We conclude that TLR9 does not mediate renal dysfunction following either moderate or severe renal ischemia. In contrast, our data indicates that TLR9 is an important mediator of hepatic injury secondary to ischemic acute kidney injury.

  4. Influence of remote ischemic conditioning and tramadol hydrochloride on oxidative stress in kidney ischemia/reperfusion injury in rats.

    Science.gov (United States)

    Oliveira, Rita de Cássia Silva de; Brito, Marcus Vinicius Henriques; Ribeiro, Rubens Fernando Gonçalves; Oliveira, Leonam Oliver Durval; Monteiro, Andrew Moraes; Brandão, Fernando Mateus Viegas; Cavalcante, Lainy Carollyne da Costa; Gouveia, Eduardo Henrique Herbster; Henriques, Higor Yuri Bezerra

    2017-03-01

    To evaluate the effects of tramadol hydrochloride associated to remote ischemic perconditioning on oxidative stress. Twenty five male rats (Wistar) underwent right nephrectomy and were distributed into five groups: Sham group (S); Ischemia/Reperfusion group (I/R) with 30 minutes of renal ischemia; Remote ischemic perconditioning group (Per) with three cycles of 10 minutes of I/R performed during kidney ischemia; Tramadol group (T) treated with tramadol hydrochloride (40mg/kg); remote ischemic perconditioning + Tramadol group (Per+T) with both treatments. Oxidative stress was assessed after 24 hours of reperfusion. Statistical differences were observed in MDA levels between I/R group with all groups (pTramadol with Sham, Per and Per+T groups (ptramadol or association of both treatments.

  5. Reperfusion Therapies of Acute Ischemic Stroke: potentials and failures

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    Georgios eTsivgoulis

    2014-12-01

    Full Text Available Over the past twenty years clinical research has focused on the development of reperfusion therapies for acute ischemic stroke (AIS, which include the use of systemic intravenous thrombolytics (alteplase, desmoteplase or tenecteplase, the augmentation of systemic intravenous recanalization with ultrasound, the bridging of intravenous with intra-arterial thrombolysis, the use of multi-modal approaches to reperfusion including thrombectomy and thromboaspiration with different available retrievers. Clinical trials testing these acute reperfusion therapies provided novel insight regarding the comparative safety and efficacy, but also raised new questions and further uncertainty on the field. Intravenous alteplase (tPA remains the fastest and easiest way to initiate acute stroke reperfusion treatment, and should continue to be the first-line treatment for patients with AIS within 4.5 hours from onset. The use of tenecteplase instead of tPA and the augmentation of systemic thrombolysis with ultrasound are both novel therapeutical modalities that may emerge as significant options in AIS treatment. Endovascular treatments for AIS are rapidly evolving due to technological advances in catheter-based interventions and are currently emphasizing speed in order to result in timely restoration of perfusion of still-salvageable, infracted brain tissue, since delayed recanalization of proximal intracranial occlusions has not been associated with improved clinical outcomes. Comprehensive imaging protocols in AIS may enable better patient selection for endovascular interventions and for testing multi-modal combinatory strategies.

  6. Protective effects of tumor necrosis factor antibody and ulinastatin on liver ischemic reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Yan-Ling Yang; Ji-Peng Li; Xiao-Ping Xu; Ke-Feng Dou; Shu-Qiang Yue; Kai-Zong Li

    2004-01-01

    AIM: To study the protective effects of tumor necrosis factor α(TNFα) antibody and ulinastatin on liver ischemic reperfusion in rats.METHODS: One hundred and twenty male SD rats were randomly divided into four groups: normal control group,ischemic group, TNFα antibody group and TNFα antibody + ulinastatin group. The animals were killed at 0, 3, 6, 9,12 h after ischemia for 60 min and followed by reperfusion.Serum alanine aminotransferase (ALT), malondialdehyde (MDA) and liver histopathology were observed.RESULTS: After ischemic reperfusion, the serum ALT and MDA were remarkably increased, and the hepatic congestion was obvious. Treatment of TNFα antibody and ulinastatin could significantly decrease serum ALT and MDA levels,and relieve hepatic congestion.CONCLUSION: Ulinastatin and TNFα antibody can suppress the inflammatory reaction induced by hepatic ischemic reperfusion, and have protective effects on rat hepatic ischemic reperfusion injury.

  7. Endovascular reperfusion therapies for acute ischemic stroke: dissecting the evidence.

    Science.gov (United States)

    Tsivgoulis, Georgios; Safouris, Apostolos; Krogias, Christos; Arthur, Adam S; Alexandrov, Andrei V

    2016-05-01

    Ischemic stroke is a major cause of death and disability and intravenous thrombolysis has been the only approved acute reperfusion therapy (RT) for many years. Seven randomized-controlled clinical trials (RCTs) evaluating the safety and efficacy of endovascular therapy in patients with acute ischemic stroke (AIS) due to emergent large vessel occlusion (ELVO) have been recently published. These studies have changed the treatment paradigm by establishing mechanical thrombectomy (MT) as the most effective acute stroke therapy for improving functional outcome in anterior circulation ELVO with a NNT of 6. The present review will critically evaluate the results of these RCTs and of the existing meta-analyses investigating the safety and efficacy of endovascular therapy for AIS. Points of debate such as acute stroke imaging, posterior circulation stroke and general anesthesia will be addressed. We will also discuss health policies aiming to increase the availability of endovascular treatment for stroke patients.

  8. Effect of N-desulfated heparin on hepatic/renal ischemia reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Tong Zhou; Jin-Lian Chen; Wei Song; Feng Wang; Ming-Jun Zhang; Pei-Hua Ni; Jian-Guo Geng

    2002-01-01

    AIM: To investigate the effect of N-desulfated heparin onhepatic/renal ischemia and reperfusion injury in rats.METHODS: Using rat models of 60 minutes hepatic or renalischemia followed by 1 h,3 h,6 h and 24 h reperfusion,animalswere randomly divided into following groups,the shamoperated controls,ischemic group receiving only normalsaline,and treated group receiving N-desulfated heparin ata dose of 12 mg/kg at 5 minutes before reperfusion. P-selectin expression was detected in bepatic/renal tissueswith immunohistochemistry methodRESULTS: P-selectin expression, serum ALT, AST, BUN andCr levels were significantly increased during 60 minuteischemia and 1 h, 3 h, 6 h and 24 h reperfusion,while theincrement was significantly inhibited,and hepatic/renalpathology observed by light microscopy was remarkablyimproved by treatment with the N-desulfated heparin.Furthermore,the heparin was found no effects on PT and KPTT.CONCLUSION: P-selectin might mediate neutrophilinfiltration and contribute to hepatic/renal ischemia andreperfusion. The N-desulfated heparin might preventhepatic/renal damage induced by ischemia and reperfusioninjury without significant anticoagulant activity.

  9. Protective effects of remote ischemic preconditioning in rat hindlimb on ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Ying Zhang; Xiangrong Liu; Feng Yan; Lianqiu Min; Xunming Ji; Yumin Luo

    2012-01-01

    Three cycles of remote ischemic pre-conditioning induced by temporarily occluding the bilateral femoral arteries (10 minutes) prior to 10 minutes of reperfusion were given once a day for 3 days before the animal received middle artery occlusion and reperfusion surgery. The results showed that brain infarct volume was significantly reduced after remote ischemic pre-conditioning. Scores in the forelimb placing test and the postural reflex test were significantly lower in rats having undergone remote ischemic pre-conditioning compared with those who did not receive remote ischemic pre-conditioning. Thus, neurological function was better in rats having undergone remote ischemic pre-conditioning compared with those who did not receive remote ischemic pre-conditioning. These results indicate that remote ischemic pre-conditioning in rat hindlimb exerts protective effects in ischemia-reperfusion injury.

  10. Comparison of the effects of dexmedetomidine administered at two different times on renal ischemia/reperfusion injury in rats

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    Edip Gonullu

    2014-06-01

    Full Text Available Background and objectives: We investigated the effect of dexmedetomidine on ischemic renal failure in rats. Methods: In the present study, 26 male adult Wistar albino rats weighting 230-300 g were randomly separated into four groups: sham-operated (n = 5, ischemia reperfusion (IR (IR group, n = 7, IR/reperfusion treatment with dexmedetomidine (Dex. R group, n = 7 and IR/pre-ischemic treatment with dexmedetomidine (Dex. I group, n = 7. In the first group, sham operation was achieved and renal clamps were not applied. For the IR group, renal ischemia was induced by occlusion of the bilateral renal arteries and veins for 60 min followed by reperfusion for 24 h. For the Dex. R and Dex. I groups, the same surgical procedure as in the IR group was performed, and dexmedetomidine (100 mcg/kg intraperitoneal was administrated at the 5th min after reperfusion and before ischemia. At the end of reperfusion, blood samples were drawn, the rats were sacrificed, and the left kidney was processed for histopathology. Results: The blood urea nitrogen (BUN levels in groups Dex. R and Dex. I were significantly lower than in the IR group (p = 0.015, p = 0.043, although urine flow was significantly higher in group Dex. R (p = 0.003. The renal histopathological score in the IR group was significantly higher than in the other groups. There was no significant difference between the Dex. R and Dex. I groups. Conclusions: The results were shown that administration of dexmedetomidine reduced the renal IR injury histomorphologically. Administration of dexmedetomidine in the reperfusion period was considered as more effective due to increase in urinary output and decrease in BUN levels.

  11. Ischemic Postconditioning and Subanesthetic S(+)-Ketamine Infusion: Effects on Renal Function and Histology in Rats

    Science.gov (United States)

    de Resende, Marco A. C.; Pantoja, Alberto V.; Barcellos, Bruno M.; Reis, Eduardo P.; Consolo, Thays D.; Módolo, Renata P.; Domingues, Maria A. C.; Assad, Alexandra R.; Cavalcanti, Ismar L.; Castiglia, Yara M. M.; Módolo, Norma S. P.

    2015-01-01

    Background. Ischemic postconditioning (IP) in renal Ischemia reperfusion injury (IRI) models improves renal function after IRI. Ketamine affords significant benefits against IRI-induced acute kidney injury (AKI). The present study investigated the effects of IP and IP associated with subanesthetic S(+)-ketamine in ischemia-reperfusion-induced AKI. Methods. Forty-one Wistar rats were randomized into four groups: CG (10), control; KG (10), S(+)-ketamine infusion; IPG (10), IP; and KIPG (11), S(+)-ketamine infusion + IP. All rats underwent right nephrectomy. IRI and IP were induced only in IPG and KIPG by left kidney arterial occlusion for 30 min followed by reperfusion for 24 h. Complete reperfusion was preceded by three cycles of 2 min of reocclusion followed by 2 min of reperfusion. Renal function was assessed by measuring serum neutrophil gelatinase-associated lipocalin (NGAL), creatinine, and blood urea nitrogen (BUN). Tubular damage was evaluated by renal histology. Results. Creatinine and BUN were significantly increased. Severe tubular injury was only observed in the groups with IRI (IPG and KIPG), whereas no injury was observed in CG or KG. No significant differences were detected between IPG and KIPG. Conclusions. No synergic effect of the use of subanesthetic S(+)-ketamine and IP on AKI was observed in this rat model. PMID:26413552

  12. Ischemic Postconditioning and Subanesthetic S(+-Ketamine Infusion: Effects on Renal Function and Histology in Rats

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    Marco A. C. de Resende

    2015-01-01

    Full Text Available Background. Ischemic postconditioning (IP in renal Ischemia reperfusion injury (IRI models improves renal function after IRI. Ketamine affords significant benefits against IRI-induced acute kidney injury (AKI. The present study investigated the effects of IP and IP associated with subanesthetic S(+-ketamine in ischemia-reperfusion-induced AKI. Methods. Forty-one Wistar rats were randomized into four groups: CG (10, control; KG (10, S(+-ketamine infusion; IPG (10, IP; and KIPG (11, S(+-ketamine infusion + IP. All rats underwent right nephrectomy. IRI and IP were induced only in IPG and KIPG by left kidney arterial occlusion for 30 min followed by reperfusion for 24 h. Complete reperfusion was preceded by three cycles of 2 min of reocclusion followed by 2 min of reperfusion. Renal function was assessed by measuring serum neutrophil gelatinase-associated lipocalin (NGAL, creatinine, and blood urea nitrogen (BUN. Tubular damage was evaluated by renal histology. Results. Creatinine and BUN were significantly increased. Severe tubular injury was only observed in the groups with IRI (IPG and KIPG, whereas no injury was observed in CG or KG. No significant differences were detected between IPG and KIPG. Conclusions. No synergic effect of the use of subanesthetic S(+-ketamine and IP on AKI was observed in this rat model.

  13. The effect of Allium sativum on ischemic preconditioning and ischemia reperfusion induced cardiac injury

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    Bhatti Rajbir

    2008-01-01

    Full Text Available In the present study, the effect of garlic (Allium sativum extract on ischemic preconditioning and ischemia-reperfusion induced cardiac injury has been studied. Hearts from adult albino rats of Wistar strain were isolated and immediately mounted on Langendorff′s apparatus for retrograde perfusion. After 15 minutes of stabilization, the hearts were subjected to four episodes of 5 min ischemia, interspersed with 5 min reperfusion (to complete the protocol of ischemic preconditioning, 30 min global ischemia, followed by 120 min of reperfusion. In the control and treated groups, respective interventions were given instead of ischemic preconditioning. The magnitude of cardiac injury was quantified by measuring Lactate Dehydrogenase and creatine kinase concentration in the coronary effluent and myocardial infarct size by macroscopic volume method. Our study demonstrates that garlic extract exaggerates the cardio protection offered by ischemic preconditioning and per se treatment with garlic extract also protects the myocardium against ischemia reperfusion induced cardiac injury.

  14. Amelioration of myocardial ischemic reperfusion injury with Calendula officinalis.

    Science.gov (United States)

    Ray, Diptarka; Mukherjee, Subhendu; Falchi, Mario; Bertelli, Aldo; Das, Dipak K

    2010-12-01

    Calendula officinalis of family Asteraceae, also known as marigold, has been widely used from time immemorial in Indian and Arabic cultures as an anti-inflammatory agent to treat minor skin wound and infections, burns, bee stings, sunburn and cancer. At a relatively high dose, calendula can lower blood pressure and cholesterol. Since inflammatory responses are behind many cardiac diseases, we sought to evaluate if calendula could be cardioprotective against ischemic heart disease Two groups of hearts were used: the treated rat hearts were perfused with calendula solution at 50 mM in KHB buffer (in mM: sodium chloride 118, potassium chloride 4.7, calcium chloride 1.7, sodium bicarbonate 25, potassium biphosphate 0.36, magnesium sulfate 1.2, and glucose 10) for 15 min prior to subjecting the heart to ischemia, while the control group was perfused with the buffer only. Calendula achieved cardioprotection by stimulating left ventricular developed pressure and aortic flow as well as by reducing myocardial infarct size and cardiomyocyte apoptosis. Cardioprotection appears to be achieved by changing ischemia reperfusion-mediated death signal into a survival signal by modulating antioxidant and anti-inflammatory pathways as evidenced by the activation of Akt and Bcl2 and depression of TNFα. The results further strengthen the concept of using natural products in degeneration diseases like ischemic heart disease.

  15. DNA damage response in renal ischemia-reperfusion and ATP-depletion injury of renal tubular cells.

    Science.gov (United States)

    Ma, Zhengwei; Wei, Qingqing; Dong, Guie; Huo, Yuqing; Dong, Zheng

    2014-07-01

    Renal ischemia-reperfusion leads to acute kidney injury (AKI) that is characterized pathologically by tubular damage and cell death, followed by tubular repair, atrophy and interstitial fibrosis. Recent work suggested the possible presence of DNA damage response (DDR) in AKI. However, the evidence is sketchy and the role and regulation of DDR in ischemic AKI remain elusive. In this study, we demonstrated the induction of phosphorylation of ATM, H2AX, Chk2 and p53 during renal ischemia-reperfusion in mice, suggesting DDR in kidney tissues. DDR was also induced in vitro during the recovery or "reperfusion" of renal proximal tubular cells (RPTCs) after ATP depletion. DDR in RPTCs was abrogated by supplying glucose to maintain ATP via glycolysis, indicating that the DDR depends on ATP depletion. The DDR was also suppressed by the general caspase inhibitor z-VAD and the overexpression of Bcl-2, supporting a role of apoptosis-associated DNA damage in the DDR. N-acetylcysteine (NAC), an antioxidant, suppressed the phosphorylation of ATM and p53 and, to a less extent, Chk2, but NAC increased the phosphorylation and nuclear foci formation of H2AX. Interestingly, NAC increased apoptosis, which may account for the observed H2AX activation. Ku55933, an ATM inhibitor, blocked ATM phosphorylation and ameliorated the phosphorylation of Chk2 and p53, but it increased H2AX phosphorylation and nuclear foci formation. Ku55933 also increased apoptosis in RPTCs following ATP depletion. The results suggest that DDR occurs during renal ischemia-reperfusion in vivo and ATP-depletion injury in vitro. The DDR is partially induced by apoptosis and oxidative stress-related DNA damage. ATM, as a sensor in the DDR, may play a cytoprotective role against tubular cell injury and death.

  16. Protective Effects of Hydrocortisone, Vitamin C and E Alone or in Combination against Renal Ischemia-Reperfusion Injury in Rat

    Science.gov (United States)

    Azari, Omid; Kheirandish, Reza; Azizi, Shahrzad; Farajli Abbasi, Mohammad; Ghahramani Gareh Chaman, Shahin; Bidi, Masoud

    2015-01-01

    Background: Renal ischemia reperfusion injury may occur in a variety of clinical situations, following a transient drop in total or regional blood flow to the kidney. This study was performed to investigate the protective effects of different antioxidants such as vitamin C, vitamin E, hydrocortisone and combination of these agents against experimental renal ischemia-reperfusion injury. Method: Thirty male rats were divided into six groups. Group Sham, Group I/R: (45 min of ischemia followed by 1h of reperfusion), Group I/R+Vit C: (50 mg/kg Vit C, IV, immediately after reperfusion), Group I/R+Vit E: (20 mg/kg Vit E, IM, 15 min before reperfusion), Group I/R+Hydrocortisone: (50 mg/kg, IV, immediately after reperfusion), and Group Combination: Ischemia-reperfusion plus combination of Vit C, E and hydrocortisone. After the experiments, the left kidney was removed and the tissues were processed for histopathological examination. Result: Severe injuries such as necrosis of tubules, atrophy of glomerulus, and hemorrhage were observed in group I/R. Histological scores indicating tissue injury significantly decreased in all treatment groups compared to the group I/R. The renal tissue in group treatment was preserved in comparison with the group I/R. Comparison between the treatment groups showed that group combination was more effective and group vit E was less effective in protecting of renal tissue against I/R injuries. Conclusion: The results demonstrated simultaneous administration of combination of Vit C, E and hydrocortisone before reperfusion of blood flow to the ischemic tissue could show a synergy against deleterious effects of I/R injuries in kidney. PMID:26351497

  17. Protective Effect of Salvia miltiorrhiza Extract Against Renal Ischemia-Reperfusion-Induced Injury in Rats

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    Gang Chen

    2012-01-01

    Full Text Available The present study investigates the effect of pre-treatment with Salvia miltiorrhiza ethanol extracts (SMEE on renal function markers, immunity and antioxidant activities in renal ischemia and reperfusion (IR rats. Wistar rat kidneys were subjected to 60 min of global ischemia at 37 °C followed by 30 min of reperfusion, and were randomly assigned into the sham, IR model and three SMEE-treated groups (n = 8 per group. Results showed that high serum creatinin (Scr, blood urea nitrogen (BUN, interleukin-6 (IL-6, interleukin-8 (IL-8, tumor necrosis factor-alpha (TNF-α and malondialhehyde (MDA levels, and low antioxidant enzyme activities were observed in IR rats compared to the sham rats. Pre-treatment of Salvia miltiorrhiza ethanol extracts for 20 days prior to IR operation improved renal function, reduced IR induced renal inflammatory and oxidative injury. It is concluded that Salvia miltiorrhiza ethanol extracts could be beneficial in the treatment of renal ischemic injury.

  18. Ischemic preconditioning increases endothelial progenitor cell number to attenuate partial nephrectomy-induced ischemia/reperfusion injury.

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    Hao Liu

    Full Text Available OBJECTIVES: The objective of this study was to investigate the role of endothelial progenitor cells (EPCs in the modulation of ischemia-reperfusion injury (IRI in a partial nephrectomy (PN rat model using early-phase ischemic preconditioning (IPC. MATERIALS AND METHODS: Ninety male Sprague-Dawley rats were randomly divided into three groups following right-side nephrectomy: Sham-operated rats (surgery without vascular clamping; PN rats (renal blood vessels were clamped for 40 min and PN was performed; and IPC rats (pretreated with 15 min ischemia and 10 min reperfusion. At 1, 3, 6, 12, 24 h, and 3 days after reperfusion, the pool of circulating EPCs and kidneys were harvested. The extent of renal injury was assessed, along with EPC number, cell proliferation, angiogenesis, and vascular growth factor expression. RESULTS: Pretreated rats exhibited significant improvements in renal function and morphology. EPC numbers in the kidneys were increased at 12 h following reperfusion in the IPC group as compared to the PN or Sham groups. Cell proliferation (including endothelial and tubular epithelial cells and angiogenesis in peritubular capillaries were markedly increased in kidneys treated with IPC. In addition, vascular endothelial growth factor-A (VEGF-A and stromal cell-derived factor-1α (SDF-1α expression in the kidneys of pretreated rats was increased compared to rats subjected to PN. CONCLUSIONS: OUR INVESTIGATION SUGGESTED THAT: (1 the early phase of IPC may attenuate renal IRI induced by PN; (2 EPCs play an important role in renal protection, involving promotion of cell proliferation and angiogenesis through release of several angiogenic factors.

  19. Delayed administration of darbepoetin or erythropoietin protects against ischemic acute renal injury and failure.

    Science.gov (United States)

    Johnson, D W; Pat, B; Vesey, D A; Guan, Z; Endre, Z; Gobe, G C

    2006-05-01

    Administration of human recombinant erythropoietin (EPO) at time of acute ischemic renal injury (IRI) inhibits apoptosis, enhances tubular epithelial regeneration, and promotes renal functional recovery. The present study aimed to determine whether darbepoetin-alfa (DPO) exhibits comparable renoprotection to that afforded by EPO, whether pro or antiapoptotic Bcl-2 proteins are involved, and whether delayed administration of EPO or DPO 6 h following IRI ameliorates renal dysfunction. The model of IRI involved bilateral renal artery occlusion for 45 min in rats (N = 4 per group), followed by reperfusion for 1-7 days. Controls were sham-operated. Rats were treated at time of ischemia or sham operation (T0), or post-treated (6 h after the onset of reperfusion, T6) with EPO (5000 IU/kg), DPO (25 mug/kg), or appropriate vehicle by intraperitoneal injection. Renal function, structure, and immunohistochemistry for Bcl-2, Bcl-XL, and Bax were analyzed. DPO or EPO at T0 significantly abrogated renal dysfunction in IRI animals (serum creatinine for IRI 0.17 +/- 0.05 mmol/l vs DPO-IRI 0.08 +/- 0.03 mmol/l vs EPO-IRI 0.04 +/- 0.01 mmol/l, P = 0.01). Delayed administration of DPO or EPO (T6) also significantly abrogated subsequent renal dysfunction (serum creatinine for IRI 0.17 +/- 0.05 mmol/l vs DPO-IRI 0.06 +/- 0.01 mmol/l vs EPO-IRI 0.03 +/- 0.03 mmol/l, P = 0.01). There was also significantly decreased tissue injury (apoptosis, P EPO at T0 or T6. These results reaffirm the potential clinical application of DPO and EPO as novel renoprotective agents for patients at risk of ischemic acute renal failure or after having sustained an ischemic renal insult.

  20. Evaluation of Early Reperfusion Criteria in Acute Ischemic Stroke

    DEFF Research Database (Denmark)

    Ozenne, Brice; Cho, Tae-Hee; Mikkelsen, Irene Klaerke;

    2015-01-01

    BACKGROUND AND PURPOSE: Though still debated, early reperfusion is increasingly used as a biomarker for clinical outcome. However, the lack of a standard definition hinders the assessment of reperfusion therapies and study comparisons. The objective was to determine the optimal early reperfusion ...

  1. Spacial and temporal profiles of neutrophil accumulation in the reperfused ischemic myocardium

    Energy Technology Data Exchange (ETDEWEB)

    de Lorgeril, M.; Rousseau, G.; Basmadjian, A.; St-Jean, G.; Tran, D.C.; Latour, J.G. (Montreal Heart Institute, Quebec (Canada))

    1990-01-01

    To elucidate further the pathogenic role of neutrophils in evolving reperfused myocardial infarction, we investigated the dynamics of their accumulation and distribution in the ischemic myocardium. The left anterior descending coronary artery was occluded in dogs for 2 hours followed by reperfusion for 0, 3, 6, or 24 hours. 111In-labeled neutrophils were injected at the time of occlusion or after 16 hours of reperfusion. The area at risk was similar among groups. Infarct size expressed in percent of the area at risk was identical between groups reperfused for 6 (35.2 +/- 4.4%) or 24 (32.3 +/- 3.9%) hours but smaller (22.0 +/- 4.4%; p less than 0.05) after 3 hours of reperfusion. 111In-neutrophils accumulation quantified by scintigraphy correlated positively with infarct size (r = 0.64, p less than 0.005); accumulation rates (cells/h/cm2MI) were high during the first 3 (2288 +/- 754) and 6 hours (1953 +/- 463) but low (490 +/- 192) between 16 and 24 hours of reperfusion. Cells accumulating during reperfusion (12,566 +/- 2307 cells/g at 3 hours) were found within the borders of the necrotic area, and the cell counts (2420 +/- 724 cells/g, p less than 0.05) in the live tissue located within the area at risk after 3 hours of reperfusion were similar to those found in the subepicardium at the onset of reperfusion: (2240 +/- 571 cells/g). Only a few cells were detected in the normally perfused myocardium (67 +/- 33 cells/g). We conclude that reperfusion accumulation in the ischemic myocardium; the reaction takes place within 3-6 hours of reperfusion, a period of time where infarct size is growing by about 40%. These results support the concept that leukocytes may play a pathogenic role on infarct size in models with brief ischemia followed by reperfusion.

  2. Spacial and temporal profiles of neutrophil accumulation in the reperfused ischemic myocardium.

    Science.gov (United States)

    de Lorgeril, M; Rousseau, G; Basmadjian, A; St-Jean, G; Tran, D C; Latour, J G

    1990-01-01

    To elucidate further the pathogenic role of neutrophils in evolving reperfused myocardial infarction, we investigated the dynamics of their accumulation and distribution in the ischemic myocardium. The left anterior descending coronary artery was occluded in dogs for 2 hours followed by reperfusion for 0, 3, 6, or 24 hours. 111In-labeled neutrophils were injected at the time of occlusion or after 16 hours of reperfusion. The area at risk was similar among groups. Infarct size expressed in percent of the area at risk was identical between groups reperfused for 6 (35.2 +/- 4.4%) or 24 (32.3 +/- 3.9%) hours but smaller (22.0 +/- 4.4%; p less than 0.05) after 3 hours of reperfusion. 111In-neutrophils accumulation quantified by scintigraphy correlated positively with infarct size (r = 0.64, p less than 0.005); accumulation rates (cells/h/cm2MI) were high during the first 3 (2288 +/- 754) and 6 hours (1953 +/- 463) but low (490 +/- 192) between 16 and 24 hours of reperfusion. Cells accumulating during reperfusion (12,566 +/- 2307 cells/g at 3 hours) were found within the borders of the necrotic area, and the cell counts (2420 +/- 724 cells/g, p less than 0.05) in the live tissue located within the area at risk after 3 hours of reperfusion were similar to those found in the subepicardium at the onset of reperfusion: (2240 +/- 571 cells/g). Only a few cells were detected in the normally perfused myocardium (67 +/- 33 cells/g). We conclude that reperfusion accumulation in the ischemic myocardium; the reaction takes place within 3-6 hours of reperfusion, a period of time where infarct size is growing by about 40%. These results support the concept that leukocytes may play a pathogenic role on infarct size in models with brief ischemia followed by reperfusion.

  3. Lipid peroxidation and renal injury in renal ischemia/reperfusion: Effect of Benincasa cerifera

    Directory of Open Access Journals (Sweden)

    Bhalodia Y

    2009-01-01

    Full Text Available To investigate the role of the methanolic fruit extract of Benincasa cerifera on lipid peroxidation (LPO and renal pathology in ischemia/reperfusion (I/R.In experimental methodology, both renal pedicles were occluded for 60 min followed by 24 h of reperfusion. B. cerifera (500 mg/kg/day was administered orally for 5 days prior to induction of renal ischemia and was continued for 1 day after ischemia. At the end of the reperfusion period, rats were sacrificed. Sham-operated rats followed same procedure except renal arteries occlusion. LPO and histopathological analysis were done in renal tissue. Serum creatinine and urea levels were measured for the evaluation of renal function. In ischemia/reperfusion (I/R rats, malondialdehyde (MDA levels were increased significantly when compared with sham-control rats. Histological changes showed tubular cell swelling, interstitial oedema, tubular dilation and moderate-to-severe necrosis in epithelium of I/R rat as compared to sham control. The methanolic fruit extract of B. cerifera could attenuate the heightened MDA levels. I/R-induced renal injury was markedly diminished by administration of B. cerifera These results indicate that the methanolic fruit extract of B. cerifera attenuate renal damage after I/R injury of the kidney by potent antioxidant or free radical scavenging activity.

  4. Remote Ischemic Conditioning and Renal Protection.

    Science.gov (United States)

    Giannopoulos, Georgios; Vrachatis, Dimitrios A; Panagopoulou, Vasiliki; Vavuranakis, Manolis; Cleman, Michael W; Deftereos, Spyridon

    2017-07-01

    Over the course of the last 2 decades, the concept of remote ischemic conditioning (RIC) has attracted considerable research interest, because RIC, in most of its embodiments offers an inexpensive way of protecting tissues against ischemic damage inflicted by a number of medical conditions or procedures. Acute kidney injury (AKI) is a common side effect in the context of various medical procedures, and RIC has been suggested as a means of reducing its incidence. Outcomes regarding kidney function have been reported in numerous studies that evaluated the effects of RIC in a variety of settings (eg, cardiac surgery, interventions requiring intravenous administration of contrast media). Although several individual studies have implied a beneficial effect of RIC in preserving kidney function, 3 recently published randomized controlled trials evaluating more than 1000 patients each (Effect of Remote Ischemic Preconditioning in the Cardiac Surgery, Remote Ischaemic Preconditioning for Heart Surgery, and ERICCA) were negative. However, AKI or any other index of renal function was not a stand-alone primary end point in any of these trials. On the other hand, a range of meta-analyses (each including thousands of participants) have reported mixed results, with the most recent among them showing benefit from RIC, pinpointing at the same time a number of shortcomings in published studies, adversely affecting the quality of available data. The present review provides a critical appraisal of the current state of this field of research. It is the opinion of the authors of this review that there is a clear need for a common clinical trial framework for ischemic conditioning studies. If the current babel of definitions, procedures, outcomes, and goals persists, it is most likely that soon ischemic conditioning will be "yesterday's news" with no definitive conclusions having been reached in terms of its real clinical utility.

  5. Enhanced phosphodiesteratic breakdown and turnover of phosphoinositides during reperfusion of ischemic rat heart.

    Science.gov (United States)

    Otani, H; Prasad, M R; Engelman, R M; Otani, H; Cordis, G A; Das, D K

    1988-11-01

    In this study, we examined phosphoinositide metabolism during ischemia and reperfusion using an isolated and perfused rat heart. When myocardial phosphoinositides were prelabeled with [3H]inositol, reperfusion after 30 minutes of normothermic global ischemia resulted in significant accumulations of radiolabeled inositol phosphate, inositol bisphosphate, and inositol trisphosphate. Isotopic incorporation of [3H]inositol into phosphatidylinositol, phosphatidylinositol-4-phosphate, and phosphatidylinositol-4,5-bisphosphate was increased significantly in the heart reperfused with [3H]inositol after 30 minutes of ischemia compared with that perfused with [3H]inositol after 30 minutes of nonischemic perfusion. However, isotopic incorporation of [3H]glycerol into diacylglycerol, phosphatidic acid, and all of the three phosphoinositides was diminished in the reperfused hearts. Reperfusion of the ischemic heart prelabeled with [14C]arachidonic acid resulted in significant increases in [14C]diacylglycerol and [14C]phosphatidic acid. The enhanced accumulations of [3H]inositol phosphates during reperfusion were not affected by treatment with prazosin plus atropine or indomethacin, but were inhibited by hypoxic reperfusion, reperfusion with Ca2+-free buffer, or by mepacrine. These results suggest that myocardial reperfusion stimulates phosphodiesteratic breakdown and turnover of phosphoinositides, and increased Ca2+ influx caused by reperfusion may be involved in the mechanism of stimulation of phosphatidylinositol-specific phospholipase C activity in the rat heart.

  6. Ouabain Contributes to Kidney Damage in a Rat Model of Renal Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Luca Villa

    2016-10-01

    Full Text Available Warm renal ischemia performed during partial nephrectomy has been found to be associated with kidney disease. Since endogenous ouabain (EO is a neuro-endocrine hormone involved in renal damage, we evaluated the role of EO in renal ischemia-reperfusion injury (IRI. We measured plasma and renal EO variations and markers of glomerular and tubular damage (nephrin, KIM-1, Kidney-Injury-Molecule-1, α1 Na-K ATPase and the protective effect of the ouabain inhibitor, rostafuroxin. We studied five groups of rats: (1 normal; (2 infused for eight weeks with ouabain (30 µg/kg/day, OHR or (3 saline; (4 ouabain; or (5 saline-infused rats orally treated with 100 µg/kg/day rostafuroxin for four weeks. In group 1, 2–3 h after IRI, EO increased in ischemic kidneys while decreased in plasma. Nephrin progressively decreased and KIM-1 mRNA increased starting from 24 h. Ouabain infusion (group 2 increased blood pressure (from 111.7 to 153.4 mmHg and ouabain levels in plasma and kidneys. In OHR ischemic kidneys at 120 h from IRI, nephrin, and KIM-1 changes were greater than those detected in the controls infused with saline (group 3. All these changes were blunted by rostafuroxin treatment (groups 4 and 5. These findings support the role of EO in IRI and suggest that rostafuroxin pre-treatment of patients before partial nephrectomy with warm ischemia may reduce IRI, particularly in those with high EO.

  7. Ouabain Contributes to Kidney Damage in a Rat Model of Renal Ischemia-Reperfusion Injury

    Science.gov (United States)

    Villa, Luca; Buono, Roberta; Ferrandi, Mara; Molinari, Isabella; Benigni, Fabio; Bettiga, Arianna; Colciago, Giorgia; Ikehata, Masami; Messaggio, Elisabetta; Rastaldi, Maria Pia; Montorsi, Francesco; Salonia, Andrea; Manunta, Paolo

    2016-01-01

    Warm renal ischemia performed during partial nephrectomy has been found to be associated with kidney disease. Since endogenous ouabain (EO) is a neuro-endocrine hormone involved in renal damage, we evaluated the role of EO in renal ischemia-reperfusion injury (IRI). We measured plasma and renal EO variations and markers of glomerular and tubular damage (nephrin, KIM-1, Kidney-Injury-Molecule-1, α1 Na-K ATPase) and the protective effect of the ouabain inhibitor, rostafuroxin. We studied five groups of rats: (1) normal; (2) infused for eight weeks with ouabain (30 µg/kg/day, OHR) or (3) saline; (4) ouabain; or (5) saline-infused rats orally treated with 100 µg/kg/day rostafuroxin for four weeks. In group 1, 2–3 h after IRI, EO increased in ischemic kidneys while decreased in plasma. Nephrin progressively decreased and KIM-1 mRNA increased starting from 24 h. Ouabain infusion (group 2) increased blood pressure (from 111.7 to 153.4 mmHg) and ouabain levels in plasma and kidneys. In OHR ischemic kidneys at 120 h from IRI, nephrin, and KIM-1 changes were greater than those detected in the controls infused with saline (group 3). All these changes were blunted by rostafuroxin treatment (groups 4 and 5). These findings support the role of EO in IRI and suggest that rostafuroxin pre-treatment of patients before partial nephrectomy with warm ischemia may reduce IRI, particularly in those with high EO. PMID:27754425

  8. Effects of ischemic preconditioning and iloprost on myocardial ischemia-reperfusion damage in rats.

    Science.gov (United States)

    Ay, Yasin; Kara, Ibrahim; Aydin, Cemalettin; Ay, Nuray Kahraman; Teker, Melike Elif; Senol, Serkan; Inan, Bekir; Basel, Halil; Uysal, Omer; Zeybek, Rahmi

    2013-01-01

    This study investigates the effects of cardiac ischemic preconditioning and iloprost on reperfusion damage in rats with myocardial ischemia/reperfusion. 38 male Wistar Albino rats used in this study were divided into 5 groups. The control group (Group 1) (n=6), ischemia/reperfusion (IR) group (Group 2) (n=8), cardiac ischemic preconditioning (CIP) group (Group 3) (n=8), iloprost (ILO) group (Group 4) (n=8), and cardiac ischemic preconditioning + iloprost (CIP+ILO) group (Group 5) (n=8). Pre-ischemia, 15 minutes post-ischemia, 45 minutes post-reperfusion, mean blood pressure (MBP), and heart rates (HR) were recorded. The rate-pressure product (RPP) was calculated. Post-reperfusion plasma creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), troponin (cTn) vlaues, and infarct size/area at risk (IS/AAR) were calculated from myocardial tissue samples. Arrhythmia and ST segment elevations were evaluated during the ischemia and reperfusion stages. Although the MBP, HR, RPP values, biochemical parameters of CK-MB and LDH levels, IS/AAR rates, ST segment elevation values were found to be similar in CIP and CIP+ILO groups and the IR and ILO groups (p>0.05), CIP-containing group values had a positively meaningful difference (pILO group. While mild-moderate findings of damage were observed in Group 3 and Group 5, severely findings of damage were releaved in Group 2 and Group 4. The arrhythmia score of the ILO group was meaningfully lower (F: 41.4, p<0.001) than the IR group. We can conclude that the effects of myocardial reperfusion damage can be reduced by cardiac ischemic preconditioning, intravenous iloprost reduced the incidence of ventricular arrhythmia associated with reperfusion, and its use with CIP caused no additional changes.

  9. 无创远程肢体缺血联合处理对大鼠肾脏急性缺血再灌注损伤的保护作用%The protective effect of noninvasive remote ischemic limb perconditioning and postconditioning combined on acute renal ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    江海波; 陈仁富; 朱海涛; 薛松; 孙晓磊; 孙晓青

    2015-01-01

    Objectives To investigate the noninvasive remote ischemic limb perconditioning and postconditioning combined on acute renal ischemia-reperfusion injury and its mechanism in rats.Results 30 healthy male SD rats were randomly divided into three groups (n =10):A is sham operation group (Sham group),B is ischemia -reperfusion group (IR),C is noninvasive remote ischemic limb perconditioning and postconditioning combined treatment group (RIperC + RIpostC group).After 24h reperfusion,serum creatinine (Cr) and urea nitrogen (BUN) levels,kidney tissue myeloperoxidase (MPO) activity,malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured and the light microscopy observed renal histological changes.Methods These indicators in group B Cr(429.52 ±29.08) μmol/L、BUN(39.05 ±2.23) mmol/L、MPO(7.31 ± 1.48) U/g、MDA (3.94± 0.48) nmol/mgprot were higher than group A Cr(103.91 ± 21.45) μ mol/L (P < 0.001)、BUN (12.20 ± 1.86) mmol/L(p <0.001)、MPO(2.25 ±0.89) U/g(P =0.009)、MDA(1.95 ±0.29) nmol/mgprot (p =0.003) while SOD(4.03 ±0.38) U/mgprut lower in group A SOD(6.819 ±0.68) U/mgprot(P =0.003) ; group C Cr(244.85 ± 40.30) μmol/L(p =0.002) 、BUN(23.48 ± 1.80) mmol/L(p <0.001) 、MPO(3.65 ±0.73) U/g(P =0.045)、MDA(2.19 ±0.31) nmol/mgprot(p =0.006) were lower than group B(P <0.05),while SOD SOD(5.71 ±0.30) U/mgprot(P =0.003) higher than in group B.Group A is normal morphology,group C is more significantly reduced than group B in morphological changes.Conclusions The noninvasive remote ischemic limb perconditioning and postconditioning combined on acute renal ischemia-reperfusion injury have significant protective effect.Through its protective effect may be transient limb ischemia-reperfusion stimulate e-ndogenous antioxidant capacity,so as to alleviate acute renal ischemia-reperfusion injury.%目的 探讨无创远程肢体缺血联合处理对大鼠肾脏急性缺血再灌注损伤的保护及作用机制.方法 30只健

  10. Dapagliflozin, SGLT2 Inhibitor, Attenuates Renal Ischemia-Reperfusion Injury

    OpenAIRE

    Yoon-Kyung Chang; Hyunsu Choi; Jin Young Jeong; Ki-Ryang Na; Kang Wook Lee; Beom Jin Lim; Dae Eun Choi

    2016-01-01

    Dapagliflozin, a new type of drug used to treat diabetes mellitus (DM), is a sodium/glucose cotransporter 2 (SGLT2) inhibitor. Although some studies showed that SGLT2 inhibition attenuated reactive oxygen generation in diabetic kidney the role of SGLT2 inhibition is unknown. We evaluated whether SLT2 inhibition has renoprotective effects in ischemia-reperfusion (IR) models. We evaluated whether dapagliflozin reduces renal damage in IR mice model. In addition, hypoxic HK2 cells were treated wi...

  11. The protective effect of erythropoietin pretreatment on ischemic acute renal failure in rats

    Institute of Scientific and Technical Information of China (English)

    Jing-Guang Liao; Min-Yan Li; Xiao-Hua Wang; Qiang Xie

    2016-01-01

    Objective: To investigate the protective effect of erythropoietin (EPO) pretreatment on ischemic acute renal failure in rats and its molecular mechanism. Methods: Male Sprague–Dawley rats were selected as experimental animals and they were randomly divided into the sham operation group (sham group), ischemia-reperfusion injury group (IRI group) and EPO pretreatment group (EPO group). Each group had 15 rats. Serum specimens and renal specimens were collected after a IRI model was built for 4, 12 and 24 h. The contents of creatinine, urea nitrogen tumor necrosis factor-alpha (TNF-a), interleukin-1 (IL-1), IL-6 and IL-8 in serum and the contents of TNF-a, IL-1, IL-6, IL-8, toll like receptor 4 (TLR4) and nuclear factor-kappa B (NF-kB) in the kidney tissue were determined. Results: After 4, 12 and 24 h reperfusion, there were differences between the contents of creatinine, urea nitrogen TNF-a, IL-1, IL-6 and IL-8 in serum and the contents of TNF-a, IL-1, IL-6, IL-8, TLR4 and NF-kB in rats of the three groups (P Conclusions: EPO pretreatment can protect the renal function of rats with ischemic acute renal failure by inhibiting the TLR4/NF-kB pathway mediated inflammatory responses.

  12. X-ray phase-contrast tomography of renal ischemia-reperfusion damage.

    Directory of Open Access Journals (Sweden)

    Astrid Velroyen

    Full Text Available The aim of the study was to investigate microstructural changes occurring in unilateral renal ischemia-reperfusion injury in a murine animal model using synchrotron radiation.The effects of renal ischemia-reperfusion were investigated in a murine animal model of unilateral ischemia. Kidney samples were harvested on day 18. Grating-Based Phase-Contrast Imaging (GB-PCI of the paraffin-embedded kidney samples was performed at a Synchrotron Radiation Facility (beam energy of 19 keV. To obtain phase information, a two-grating Talbot interferometer was used applying the phase stepping technique. The imaging system provided an effective pixel size of 7.5 µm. The resulting attenuation and differential phase projections were tomographically reconstructed using filtered back-projection. Semi-automated segmentation and volumetry and correlation to histopathology were performed.GB-PCI provided good discrimination of the cortex, outer and inner medulla in non-ischemic control kidneys. Post-ischemic kidneys showed a reduced compartmental differentiation, particularly of the outer stripe of the outer medulla, which could not be differentiated from the inner stripe. Compared to the contralateral kidney, after ischemia a volume loss was detected, while the inner medulla mainly retained its volume (ratio 0.94. Post-ischemic kidneys exhibited severe tissue damage as evidenced by tubular atrophy and dilatation, moderate inflammatory infiltration, loss of brush borders and tubular protein cylinders.In conclusion GB-PCI with synchrotron radiation allows for non-destructive microstructural assessment of parenchymal kidney disease and vessel architecture. If translation to lab-based approaches generates sufficient density resolution, and with a time-optimized image analysis protocol, GB-PCI may ultimately serve as a non-invasive, non-enhanced alternative for imaging of pathological changes of the kidney.

  13. Amino acids protects against renal ischemia-reperfusion injury and attenuates renal endothelin-1 disorder in rats

    Institute of Scientific and Technical Information of China (English)

    谢立平; 郑祥毅; 秦杰; 童炎岳

    2004-01-01

    Objective: To investigate nephroprotective effects of a mixture of 8 L-amino acids on renal ischemia-reperfusion injury and its effects on renal endothelin-1 (ET-1). Methods: The mixture of 8 L-amino acids includes glycine, alanine, threonine, serine, valine, leucine, isoleucine and proline. Acute ischemic renal injury was induced by clamping renal pedicle for 45 minutes in rats. Sixty male Sprague-Dawiey rats were randomly divided into 3 groups: a sham-operated group ( Group A, n = 8), a control group (Group B, n = 26 ) and an amino acid- treated group (Group C, n = 26 ). Amino acids were infused at a rate of 1 mi · 100g-1 · h-1 I hour before ischemia and during 3 hours of the whole reperfusion. The serum creatinine values, BUN levels, creatiulne clearance, urine sodium & potassium excretion, urine lactate dehydrogenase (LDH),the rate of urine flow and histological examination were measured. Renal ET-1 levels were assayed with radioimmunological assay (RIA) Results: The creatinine clearance was 471.0 μl/min ± 121.5 pi/main in Group C and 227.0 μl/min ± 27.0 μl/min in Group B 3 hours after reperfnsion, P < 0.01 ). The urine flow rate was 63.6 pi/min ± 15.2 μl/min in Group C and 24.3 μl/min ± 7.7 μl/minin Group B, P < 0.01 ) 1.5 hours after reperfusion. The serum creatinine was 85.0 μl/min ± 7.7 μmol/L and BUN oncentration11.4 mmol/L ±3.9 mmol/L in Group C and 112.7 μmol/L ± 19.5 μmol/L and 20.7 mmol/L ± 6.6 mmol/L respectively in Group B after 24 hours of reperfusion (P < 0.05) . The mean histological score by standards of Paller in kidneys was 108.7 ± 15.7 in Group C, and 168.8 ± 14.8 in Group B (P < 0.01 ). The renal ET-1 levels 15 minute and 3 hours after reperfusion were 7.2 pg/mg ± 0.8 pg/mg and 9.6 pg/ml ± 1.0 pg/ml in Group C , and 10.1 pg/ml ± 2.8 pg/ml and 13.0 pg/ml ± 2.7 pg/mi in Group B ( P < 0.01). Conclusions: The mixture of 8 L-amino acids can provide remarkable protection against renal isehemia- reperfusion injury

  14. Genistein attenuates ischemia/reperfusion injury in rat kidneys via ...

    African Journals Online (AJOL)

    by oral gavage for 7 consecutive days and then subjected to 45 min of renal bilateral ... Keywords: Oxidative stress, Genistein, Ischemic reperfusion injury, Renal ... radical production ultimately leading to cellular ... serum biomarker analysis.

  15. Kidney Injury Molecule-1 Protects against Gα12 Activation and Tissue Damage in Renal Ischemia-Reperfusion Injury

    Science.gov (United States)

    Ismail, Ola Z.; Zhang, Xizhong; Wei, Junjun; Haig, Aaron; Denker, Bradley M.; Suri, Rita S.; Sener, Alp; Gunaratnam, Lakshman

    2016-01-01

    Ischemic acute kidney injury is a serious untreatable condition. Activation of the G protein α12 (Gα12) subunit by reactive oxygen species is a major cause of tissue damage during renal ischemia-reperfusion injury. Kidney injury molecule-1 (KIM-1) is a transmembrane glycoprotein that is highly up-regulated during acute kidney injury, but the physiologic significance of this up-regulation is unclear. Here, we report for the first time that Kim-1 inhibits Gα12 activation and protects mice against renal ischemia-reperfusion injury. We reveal that Kim-1 physically interacts with and inhibits cellular Gα12 activation after inflammatory stimuli, including reactive oxygen species, by blocking GTP binding to Gα12. Compared with Kim-1+/+ mice, Kim-1−/− mice exhibited greater Gα12 and downstream Src activation both in primary tubular epithelial cells after in vitro stimulation with H2O2 and in whole kidneys after unilateral renal artery clamping. Finally, we show that Kim-1–deficient mice had more severe kidney dysfunction and tissue damage after bilateral renal artery clamping, compared with wild-type mice. Our results suggest that KIM-1 is an endogenous protective mechanism against renal ischemia-reperfusion injury through inhibition of Gα12. PMID:25759266

  16. Effects of ulinastatin on renal ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Cong-cong CHEN; Zi-ming LIU; Hui-hua WANG; Wei HE; Yi WANG; Wei-dong WU

    2004-01-01

    AIM: To investigate the effect and possible mechanism of ulinastatin on renal ischemia-reperfusion injury in rats.METHODS: Male Sprague-Dawley rats were subjected to 45-min bilateral renal ischemia, treated with intravenously 12 500 U ulinastatin at 30 min prior to ischemia and at the beginning of reperfusion, compared with a nontreated group without ulinastatin and a sham-operation group without bilateral renal ischemia. After 0 h, 2 h, 6 h, 12 h, and 24 h of reperfusion, serum creatinine and blood urea nitrogen were measured for the assessment of renal function, renal sections were used for histologic grading of renal injury, for immunohistochemical localization of Bcl-2 and heat shock protein 70. Renal ultrastructure was observed through a transmission electron microscope.RESULTS: Ulinastatin significantly reduced the increase in blood urea nitrogen and creatinine produced by renal ischemia-reperfusion, suggesting an improvement in renal function. Ulinastatin reduced the histologic evidence of renal damage associated with ischemia-reperfusion and accompanied with an up-regulation in the expression of Bcl-2 protein, but it had no significent effect on the expression of HSP 70. Ulinastatin also significantly reduced kidney ultrastructure damage caused by renal ischemia-reperfusion. CONCLUSION: The protease inhibitor, ulinastatin,reduced the renal dysfunction and injury associated with ischemia-reperfusion of the kidney. The protective effect of ulinastatin might be associated with the up-regulation of Bcl-2 expression and the effect on membrane fragility.

  17. Cytoprotective roles of GSH, SOD and solcoseryl against ischemic damage and reperfusion injury to warm ischemic lung. Study of Canine warm ischemic lung.

    OpenAIRE

    Taniguchi, Hideki; Kawahara, Katsunobu; Nakasone, Tomonori; Ikari, Hideki; Honjoh, Seiji; Hisano, Hiroshi; Takahashi, Takao; Kusano, Hiroyuki; Ayabe, Hiroyoshi; Tomita, Masao

    1990-01-01

    This study was performed to clarify the roles of reduced glutathion (GSH), superoxide dismutase (SOD), and solcosaryl in ischemic damage and reperfusion injury to the warm ischemic lungs of experimental animals. Fifty-one warm ischemic canine lungs were made by hilar stripping and clamping of the left PA, PV and bronchus for 2-3 hours. In the Non-perfusion group, GSH (50mg/ kg, I. V.: Group II) and solcoseryl (50mg/kg, I. V.: Group III) were administered. In the perfusion group, Euro-Collins ...

  18. Ischemic postconditioning enhances glycogen synthase kinase-3β expression and alleviates cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Bo Zhao; Wenwei Gao; Jiabao Hou; Yang Wu; Zhongyuan Xia

    2012-01-01

    The present study established global brain ischemia using the four-vessel occlusion method.Following three rounds of reperfusion for 30 seconds,and occlusion for 10 seconds,followed by reperfusion for 48 hours,infarct area,the number of TUNEL-positive cells and Bcl-2 expression were significantly reduced.However,glycogen synthase kinase-3β activity,cortical Bax and caspase-3 expression significantly increased,similar to results following ischemic postconditioning.Our results indicated that ischemic postconditioning may enhance glycogen synthase kinase-3β activity,a downstream molecule of the phosphatase and tensin homolog deleted on chromosome 10/phosphatidylinositol 3-kinase/protein kinase B signaling pathway,which reduces caspase-3 expression to protect the brain against ischemic injury.

  19. Ascorbic acid against reperfusion injury in human renal transplantation.

    Science.gov (United States)

    Norio, Karri; Wikström, Mårten; Salmela, Kaija; Kyllönen, Lauri; Lindgren, Leena

    2003-08-01

    The cadaveric renal graft is exposed to ischaemic injury during preservation and to oxidative damage during reperfusion. Both these mechanisms are known to cause cell damage, which may impair graft function. Reperfusion injury (RPI) is mediated by reactive oxygen species (ROS). Ascorbic acid (AA) is a potent physiological extracellular scavenger of ROS. We perfused 31 renal grafts immediately before implantation with a solution of Euro-Collins containing 0.5 mg/ml of AA to diminish RPI. From every donor, the contralateral kidney served as a control. The control grafts were perfused with the same perfusion as those of the AA group, only without the AA substitution. We assessed the effect of AA by recording serum creatinine, creatinine clearance, initial graft function and early rejections. The incidence of delayed graft function (DGF) was 32% in the AA group, and 29% in the control group. Other parameters were also similar in both groups, except for the length of DGF, which showed a trend towards a shorter duration in the AA group. The pre-operative systemic AA concentration was significantly ( P=0.01) lower in the haemodialysis patients than in those on peritoneal dialysis. In conclusion, this clinical study could not demonstrate significant benefits of AA in renal transplantation.

  20. Unilateral Renal Ischemia-Reperfusion as a Robust Model for Acute to Chronic Kidney Injury in Mice.

    Directory of Open Access Journals (Sweden)

    Nathalie Le Clef

    Full Text Available Acute kidney injury (AKI is an underestimated, yet important risk factor for development of chronic kidney disease (CKD. Even after initial total recovery of renal function, some patients develop progressive and persistent deterioration of renal function and these patients are more likely to progress to end-stage renal disease (ESRD. Animal models are indispensable for unravelling the mechanisms underlying this progression towards CKD and ESRD and for the development of new therapeutic strategies in its prevention or treatment. Ischemia (i.e. hypoperfusion after surgery, bleeding, dehydration, shock, or sepsis is a major aetiology in human AKI, yet unilateral ischemia-reperfusion is a rarely used animal model for research on CKD and fibrosis. Here, we demonstrate in C57Bl/6J mice, by both histology and gene expression, that unilateral ischemia-reperfusion without contralateral nephrectomy is a very robust model to study the progression from acute renal injury to long-term tubulo-interstitial fibrosis, i.e. the histopathological hallmark of CKD. Furthermore, we report that the extent of renal fibrosis, in terms of Col I, TGFβ, CCN2 and CCN3 expression and collagen I immunostaining, increases with increasing body temperature during ischemia and ischemia-time. Thus, varying these two main determinants of ischemic injury allows tuning the extent of the long-term fibrotic outcome in this model. Finally, in order to cover the whole practical finesse of ischemia-reperfusion and allow model and data transfer, we provide a referenced overview on crucial technical issues (incl. anaesthesia, analgesia, and pre- and post-operative care with the specific aim of putting starters in the right direction of implementing ischemia in their research and stimulate them, as well as the community, to have a critical view on ischemic literature data.

  1. Unilateral Renal Ischemia-Reperfusion as a Robust Model for Acute to Chronic Kidney Injury in Mice.

    Science.gov (United States)

    Le Clef, Nathalie; Verhulst, Anja; D'Haese, Patrick C; Vervaet, Benjamin A

    2016-01-01

    Acute kidney injury (AKI) is an underestimated, yet important risk factor for development of chronic kidney disease (CKD). Even after initial total recovery of renal function, some patients develop progressive and persistent deterioration of renal function and these patients are more likely to progress to end-stage renal disease (ESRD). Animal models are indispensable for unravelling the mechanisms underlying this progression towards CKD and ESRD and for the development of new therapeutic strategies in its prevention or treatment. Ischemia (i.e. hypoperfusion after surgery, bleeding, dehydration, shock, or sepsis) is a major aetiology in human AKI, yet unilateral ischemia-reperfusion is a rarely used animal model for research on CKD and fibrosis. Here, we demonstrate in C57Bl/6J mice, by both histology and gene expression, that unilateral ischemia-reperfusion without contralateral nephrectomy is a very robust model to study the progression from acute renal injury to long-term tubulo-interstitial fibrosis, i.e. the histopathological hallmark of CKD. Furthermore, we report that the extent of renal fibrosis, in terms of Col I, TGFβ, CCN2 and CCN3 expression and collagen I immunostaining, increases with increasing body temperature during ischemia and ischemia-time. Thus, varying these two main determinants of ischemic injury allows tuning the extent of the long-term fibrotic outcome in this model. Finally, in order to cover the whole practical finesse of ischemia-reperfusion and allow model and data transfer, we provide a referenced overview on crucial technical issues (incl. anaesthesia, analgesia, and pre- and post-operative care) with the specific aim of putting starters in the right direction of implementing ischemia in their research and stimulate them, as well as the community, to have a critical view on ischemic literature data.

  2. RGS4 inhibits angiotensin II signaling and macrophage localization during renal reperfusion injury independent of vasospasm.

    Science.gov (United States)

    Pang, Paul; Jin, Xiaohua; Proctor, Brandon M; Farley, Michelle; Roy, Nilay; Chin, Matthew S; von Andrian, Ulrich H; Vollmann, Elisabeth; Perro, Mario; Hoffman, Ryan J; Chung, Joseph; Chauhan, Nikita; Mistri, Murti; Muslin, Anthony J; Bonventre, Joseph V; Siedlecki, Andrew M

    2015-04-01

    Vascular inflammation is a major contributor to the severity of acute kidney injury. In the context of vasospasm-independent reperfusion injury we studied the potential anti-inflammatory role of the Gα-related RGS protein, RGS4. Transgenic RGS4 mice were resistant to 25 min injury, although post-ischemic renal arteriolar diameter was equal to the wild type early after injury. A 10 min unilateral injury was performed to study reperfusion without vasospasm. Eighteen hours after injury, blood flow was decreased in the inner cortex of wild-type mice with preservation of tubular architecture. Angiotensin II levels in the kidneys of wild-type and transgenic mice were elevated in a sub-vasoconstrictive range 12 and 18 h after injury. Angiotensin II stimulated pre-glomerular vascular smooth muscle cells (VSMCs) to secrete the macrophage chemoattractant RANTES, a process decreased by angiotensin II R2 (AT2) inhibition. However, RANTES increased when RGS4 expression was suppressed implicating Gα protein activation in an AT2-RGS4-dependent pathway. RGS4 function, specific to VSMC, was tested in a conditional VSMC-specific RGS4 knockout showing high macrophage density by T2 MRI compared with transgenic and non-transgenic mice after the 10 min injury. Arteriolar diameter of this knockout was unchanged at successive time points after injury. Thus, RGS4 expression, specific to renal VSMC, inhibits angiotensin II-mediated cytokine signaling and macrophage recruitment during reperfusion, distinct from vasomotor regulation.

  3. Combination of tadalafil and diltiazem attenuates renal ischemia reperfusion-induced acute renal failure in rats.

    Science.gov (United States)

    El-Sisi, Alaa E; Sokar, Samia S; Abu-Risha, Sally E; Ibrahim, Hanaa A

    2016-12-01

    Life threatening conditions characterized by renal ischemia/reperfusion (RIR) such as kidney transplantation, partial nephrectomy, renal artery angioplasty, cardiopulmonary bypass and aortic bypass surgery, continue to be among the most frequent causes of acute renal failure. The current study investigated the possible protective effects of tadalafil alone and in combination with diltiazem in experimentally-induced renal ischemia/reperfusion injury in rats. Possible underlying mechanisms were also investigated such as oxidative stress and inflammation. Rats were divided into sham-operated and I/R-operated groups. Anesthetized rats (urethane 1.3g/kg) were subjected to bilateral ischemia for 30min by occlusion of renal pedicles, then reperfused for 6h. Rats in the vehicle I/R group showed a significant (p˂0.05) increase in kidney malondialdehyde (MDA) content; myeloperoxidase (MPO) activity; TNF-α and IL-1β contents. In addition significant (p˂0.05) increase in intercellular adhesion molecule-1(ICAM-1) content, BUN and creatinine levels, along with significant decrease in kidney superoxide dismutase (SOD) activity. In addition, marked diffuse histopathological damage and severe cytoplasmic staining of caspase-3 were detected. Pretreatment with combination of tadalafil (5mg/kg bdwt) and diltiazem (5mg/kg bdwt) resulted in reversal of the increased biochemical parameters investigated. Also, histopathological examination revealed partial return to normal cellular architecture. In conclusion, pretreatment with tadalafil and diltiazem combination protected against RIR injury.

  4. Ischemic Postconditioning Protects Neuronal Death Caused by Cerebral Ischemia and Reperfusion via Attenuating Protein Aggregation

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    Jianmin Liang, Jihang Yao, Guangming Wang, Ying Wang, Boyu Wang, Pengfei Ge

    2012-01-01

    Full Text Available Objective: To investigate the effect of ischemic postconditioning on protein aggregation caused by transient ischemia and reperfusion and to clarify its underlying mechanism.Methods: Two-vessel-occluded transient global ischemia rat model was used. The rats in ischemic postconditioning group were subjected to three cycles of 30-s/30-s reperfusion/clamping after 15min of ischemia. Neuronal death in the CA1 region was observed by hematoxylin-eosin staining, and number of live neurons was assessed by cell counting under a light microscope. Succinyl-LLVY-AMC was used as substrate to assay proteasome activity in vitro. Protein carbonyl content was spectrophotometrically measured to analyze protein oxidization. Immunochemistry and laser scanning confocal microscopy were used to observe the distribution of ubiquitin in the CA1 neurons. Western blotting was used to analyze the quantitative alterations of protein aggregates, proteasome, hsp70 and hsp40 in cellular fractions under different ischemic conditions.Results: Histological examination showed that the percentage of live neurons in the CA1 region was elevated from 5.21%±1.21% to 55.32%±5.34% after administration of ischemic postconditioning (P=0.0087. Western blotting analysis showed that the protein aggregates in the ischemia group was 32.12±4.87, 41.86±4.71 and 34.51±5.18 times higher than that in the sham group at reperfusion 12h, 24h and 48h, respectively. However, protein aggregates were alleviated significantly by ischemic postconditioning to 2.84±0.97, 13.72±2.13 and 14.37±2.42 times at each indicated time point (P=0.000032, 0.0000051 and 0.0000082. Laser scanning confocal images showed ubiquitin labeled protein aggregates could not be discerned in the ischemic postconditioning group. Further study showed that ischemic postconditioning suppressed the production of carbonyl derivatives, elevated proteasome activity that was damaged by ischemia and reperfusion, increased the expression

  5. Ischemic post-conditioning attenuates the intestinal injury induced by limb ischemia/reperfusion in rats

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    Y.F. Leng

    2011-05-01

    Full Text Available The purpose of this study was to investigate the protective effects of ischemic post-conditioning on damage to the barrier function of the small intestine caused by limb ischemia-reperfusion injury. Male Wistar rats were randomly divided into 3 groups (N = 36 each: sham operated (group S, lower limb ischemia-reperfusion (group LIR, and post-conditioning (group PC. Each group was divided into subgroups (N = 6 according to reperfusion time: immediate (0 h; T1, 1 h (T2, 3 h (T3, 6 h (T4, 12 h (T5, and 24 h (T6. In the PC group, 3 cycles of reperfusion followed by ischemia (each lasting 30 s were applied immediately. At all reperfusion times (T1-T6, diamine oxidase (DAO, superoxide dismutase (SOD, and myeloperoxidase (MPO activity, malondialdehyde (MDA intestinal tissue concentrations, plasma endotoxin concentrations, and serum DAO, tumor necrosis factor-α (TNF-α, and interleukin-10 (IL-10 concentrations were measured in sacrificed rats. Chiu’s pathology scores for small intestinal mucosa were determined under a light microscope and showed that damage to the small intestinal mucosa was lower in group PC than in group LIR. In group PC, tissue DAO and SOD concentrations at T2 to T6, and IL-10 concentrations at T2 to T5 were higher than in group LIR (P < 0.05; however, tissue MPO and MDA concentrations, and serum DAO and plasma endotoxin concentrations at T2 to T6, as well as TNF-α at T2 and T4 decreased significantly (P < 0.05. These results show that ischemic post-conditioning attenuated the permeability of the small intestines after limb ischemia-reperfusion injury. The protective mechanism of ischemic post-conditioning may be related to inhibition of oxygen free radicals and inflammatory cytokines that cause organ damage.

  6. The protective activity of noscapine on renal ischemia–reperfusion injury in male Wistar rat

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    Mehrangiz Khanmoradi; Seyyed Ali Mard; Nahid Aboutaleb; Malihe Nobakht; Masoud Mahmoudian

    2014-01-01

    Objective(s): Bradykinin is a part of the kinin-kallikrein system which is involved in ischemia-reperfusion injury via B1 and B2 receptors. Noscapine is a non-competitive antagonist of bradykinin receptors. Noscapine has been reported to to be able to protect some organs against ischemia-reperfusion injury but its effect on renal ischemia-reperfusion injury (RIR) in rats is unknown. Therefore, the present study was designed to evaluate the effect of noscapine on renal ischemia-reperfusion inj...

  7. Ischemic Postconditioning Alleviates Brain Edema After Focal Cerebral Ischemia Reperfusion in Rats Through Down-Regulation of Aquaporin-4.

    Science.gov (United States)

    Han, Dong; Sun, Miao; He, Ping-Ping; Wen, Lu-Lu; Zhang, Hong; Feng, Juan

    2015-07-01

    Cerebral edema is a serious complication associated with cerebral ischemia/reperfusion (I/R). Aquaporin-4 (AQP4) plays a role in generating postischemic edema after reperfusion. Recently, ischemic postconditioning (Postcond) has been shown to produce neuroprotective effects and reduce brain edema in rats after cerebral I/R. It is unclear if ischemic Postcond alleviates brain edema injury through regulation of AQP4. In this study, middle cerebral artery occlusion (MCAO) was induced in rats by filament insertion for 2 h following 24-h reperfusion: ischemic Postcond treatment was performed before reperfusion in the experimental group. We used the wet-dry weight ratio and transmission electron microscopy to evaluate brain edema after 24 h of reperfusion. We used immunohistochemistry and Western blot analyses to evaluate the distribution and expression of AQP4. Ischemic Postcond significantly reduced the water content of the brain tissue and swelling of the astrocytic foot processes. AQP4 expression increased in the I/R and Postcond groups compared to the sham group, but it decreased in the Postcond group compared to the I/R group. The results of our study suggest that ischemic Postcond effectively reduces brain edema after reperfusion by inhibiting AQP4 expression. The data in this study support the use of ischemic Postcond for alleviating brain edema after cerebral I/R.

  8. Role of mitochondrial KATP channel in reduction of renal ischemia- reperfusion injury by ischemic postconditioning in rats%mito-KATP通道在缺血后处理减轻大鼠肾缺血再灌注损伤中的作用

    Institute of Scientific and Technical Information of China (English)

    张维亮; 赵砚丽; 刘晓明; 张东; 岳立辉

    2010-01-01

    Objective To investigate the role of mitochondrial KATP (mito-KATP) channel in reduction of renal ischemia-repeerfusion (I/R) injury by ischemic postconditioning (IPo) in rats. Methods Thirty-five adult male SD rats weighing 250-280 g were randomly divided into 5 groups ( n = 7 each): group Ⅰ sham operation (group S); group Ⅱ I/R; group Ⅲ IPo; group Ⅳ 5-HD + I/R and group V 5-HD + IPo. The rats were anesthetized with intraperitoneal (IP) chloral hydrate 300 mg/kg. Bilateral kidneys were exposed and their pedicles were occluded for 45 min with atraumatic mini-clamp followed by 6 h reperfusion in group Ⅱ - Ⅴ . In group Ⅲ and Ⅴ 3 cycles of 10 s reperfusion followed by 10 s ischemia were applied immediately after 45 min kidney ischemia. In group Ⅳ and Ⅴ 5-HD (a specific blocker of the mito-KATP channel) 10 mg/kg was given IP at 30 min before ischemia. Blood samples were obtained at 6 h of reperfusion for determination of serum creatinine (Cr) and urea nitrogen (BUN) concentrations. The animals were then killed. Bilateral kidneys were removed for determination of mitochondrial membrane potential in the renal tubular epidural cell and intracellular reactive oxygen species (ROS)content and free Ca2+ concentrations. Results Renal I/R significantly increased serum Cr and BUN concentrations and intracellular free Ca2+ concentration and ROC content and decreased mitochondrial membrane potential as compared with sham operation group. IPo significantly attenuated the I/R-induced changes mentioned above. The protective effects of IPo against renal I/R injury was reversed by 5-HD. Conclusion Mito-KATP channel is involved in reduction of I/R-induced renal injury by ischemic postconditioning.%目的 评价线粒体ATP敏感性钾通道(mito-KATP通道)在缺血后处理减轻大鼠肾缺血再灌注损伤中的作用.方法 健康成年雄性SD大鼠35只,体重250~280 g,随机分为5组(n=7):假手术组(S组)仅分离双侧肾蒂,暴露45 min不夹闭;肾

  9. Micro RNA-320 as a novel potential biomarker in renal ischemia reperfusion.

    Science.gov (United States)

    Güçlü, Aydın; Koçak, Cengiz; Koçak, Fatma Emel; Akçılar, Raziye; Dodurga, Yavuz; Akçılar, Aydın; Seçme, Mücahit

    2016-10-01

    MicroRNAs (miR) are important diagnostic and treatment targets due to their different tissue expressions and their central position in the regulation of gene expressions. miR studies might pioneer emerging of new diagnostic tools and treatment goals in kidney diseases. Captopril (CAP) and telmisartan (TEL) were shown to be effective in ischemia reperfusion (IR) injury. There is not any study about the effect of TEL and CAP over miR-21-320-146a. Our aim was to study the effects of CAP and TEL over miR on renal IR model. We used 12-16 weeks-old Wistar-Albino rats that weigh 300-350 g. Rats (n, 6) were randomized into four groups (Control, IR, IR + CAP, IR + TEL). Urea, creatinine, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), super oxide dismutase (SOD), and miRs were analyzed. Urea, creatinine, TOS, OSI levels of IR + CAP, and IR + TEL groups were lower comparing to IR group. TAS and SOD levels were higher in IR group than IR + TEL group. miR-21-320-146a showed increase in renal IR injury. miR-320, 146a showed significant decrease in IR + CAP and IR + TEL groups comparing to IR group. We showed histopathological recovery and decreased apoptosis in IR + CAP and IR + T groups than IR group. We, for the first time in the literature, showed that miR-320 is increased in IR injury. miR-320 might be a novel diagnosis and treatment target in renal ischemic reperfusion injury. Also, for the first time, we showed that CAP and TEL cause functional and histopathological recovery and lower miR-146a and miR-320.

  10. Renal ischemia and reperfusion injury: influence of chorpromazine on renal function and lipid peroxidation Lesão de isquemia e reperfusão renal: influência da clorpromazina na função renal e na peroxidação lipídica

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    Silvio Tucci Junior

    2008-01-01

    Full Text Available PURPOSE: To evaluate the influence of chlorpromazine (CPZ on renal function and lipid peroxidation in a rat model of kidney ischemia/reperfusion injury. METHODS: Forty eight Wistar rats underwent a laparotomy for hilar clamping of left kidney with a bulldog clamp for 60 minutes followed by organ reperfusion and contralateral nephrectomy. Of these, 26 received 3mg/kg of CPZ intravenously 15 minutes before renal ischemia (G-E while the remaining 22 were used as ischemic control group (G-C. Eleven rats of G-E and 8 of G-C were followed for blood urea nitrogen and creatinine determinations before renal ischemia and at 1st, 4th and 7th postoperative days. Samplings of left renal tissue were obtained at 5 minutes (5 rats from each group and 24 hours (9 G-C and 10 of G-E of reperfusion for malondialdehy (MDA content determination. Controls of renal MDA content were determined in kidneys harvested from 6 additional normal rats. RESULTS: Acute renal failure occurred in all animals but levels of BUN and creatinine were significantly lower in G-E (p0.05 and returned near to normal levels 24 hours later. CONCLUSION: CPZ conferred partial protection of renal function to kidneys submitted to ischemia/reperfusion injury that seems to be not dependent on inhibition of lipid peroxidation.OBJETIVO: avaliar a influência da clorpromazina (CPZ na função renal e na peroxidação lipídica num modelo de lesão de isquemia/reperfusão renal em ratos. MÉTODOS: 48 ratos Wistar foram submetidos à laparotomia para clampamento da artéria renal esquerda durante 60 minutos, seguido da reperfusão e nefrectomia contralateral. Destes animais, 26 receberam 3 mg/kg de CPZ intravenosa 15 minutos antes da isquemia renal (G-E, sendo os 22 animais restantes utilizados como grupo controle isquêmico (G-C. Em 11 ratos do G-E e 8 do G-C foi feita a dosagem de uréia e creatinina sérica antes da isquemia renal e no 1º, 4º e 7º dia pós-operatório. Amostras de tecido do rim

  11. Activation of SHH signaling pathway promotes vasculogenesis in post-myocardial ischemic-reperfusion injury

    OpenAIRE

    Guo, Wei; YI, XIN; Ren, Faxin; Liu, Liwen; WU, SUNING; Yang, Jun

    2015-01-01

    This study aimed to investigate the potential roles of sonic Hedgehog (SHH) expression in vasculogenesis in post-myocardial ischemic-reperfusion injury (MIRI) and its underlying mechanism. Cardiac microvascular endothelial cells (CMECs) isolated from the SD rat hearts tissues were used to construct the MIRI model. mRNA level of SHH in control cells and MIRI cells was detected using RT-PCR analysis. Furthermore, effects of SHH expression on CMECs viability and apoptosis were analyzed using MTT...

  12. Effect of pre- and posttreatment of losartan in feline model of myocardial ischemic-reperfusion injury.

    Science.gov (United States)

    Kumari, R; Manchanda, S C; Maulik, S K

    2004-01-01

    This study investigated the differential effect of losartan, an AT1 receptor blocker, when administered in pre- and postischemic phases, on the biochemical, hemodynamic and oxidative stress associated with regional ischemic-reperfusion injury in cat. Losartan (5 microg/kg/min) or normal saline was administered intravenously in open chest barbiturate anesthetized cats, 15 min before and 10 min after the occlusion of the left anterior descending (LAD) coronary artery. The LAD was occluded for 15 min followed by 60 min reperfusion. In the saline treated group, there was significant depression of hemodynamic functions, i.e., mean arterial pressure (MAP), heart rate (HR), left ventricular end diastolic pressure (LVEDP) and left ventricular (LV) peak (+/-) dP/dt, along with depletion of adenosine triphosphate (ATP) of the affected myocardium. Oxidative stress during reperfusion injury was evidenced by significant increase in plasma thiobarbituric acid reactive substances (TBARS) accompanied by significant reduction in myocardial superoxide dismutase (SOD) activities. In both treatment groups, losartan caused recovery of all the hemodynamic parameters and repletion of ATP along with no significant change in plasma TBARS and myocardial SOD activity. There was no effect on catalase activity. Results from the study suggest that the effects of pre- and posttreatment of losartan are comparable in functional recovery of the heart from ischemic-reperfusion injury. (c) 2004 Prous Science. All rights reserved.

  13. Ischemic preconditioning and the gene expression of enteric endothelial cell biology of rats submitted to intestinal ischemia and reperfusion

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    Murched Omar Taha

    2013-03-01

    Full Text Available PURPOSE: To investigate the effects of ischemic preconditioning (IPC on the expression of pro and anti-apoptotic genes in rat endothelial cells undergoing enteric ischemia (I and reperfusion (R. METHODS: Thirty rats underwent clamping of the superior mesenteric vessels. Sham group (GS laparotomy only; Ischemia (GI: intestinal ischemia (60 min; Ischemia and Reperfusion (GIR: ischemia (60 min and reperfusion (120 min; Ischemia and intestinal ischemic preconditioning (GI + IPC : 5 minutes of ischemia followed by 10 min of reperfusion before sustained ischemia (60 min ischemia and reperfusion and IPC (GIR + IPC: 5 min ischemia followed by 10 min of reperfusion before sustained ischemia (60min and reperfusion (120 min. Rat Endothelial Cell Biology (PCR array to determine the expression of genes related to endothelial cell biology. RESULTS: Gene expression of pro-apoptotic markers (Casp1, Casp6, Cflar, Fas, and Pgl was down regulated in GI+IPC and in GIR + IPC. In contrast, the expression of anti-apoptotic genes (Bcl2 and Naip2, was up-regulated in GI + IPC and in GIR + IPC. CONCLUSION: Ischemic preconditioning may protect against cell death caused by ischemia and reperfusion.

  14. Effect of remote ischemic preconditioning on renal dysfunction after complex valvular heart surgery: a randomized controlled trial.

    Science.gov (United States)

    Choi, Yong Seon; Shim, Jae Kwang; Kim, Jong Chan; Kang, Kyu-Sik; Seo, Yong Han; Ahn, Ki-Ryang; Kwak, Young Lan

    2011-07-01

    Acute kidney injury after cardiac surgery with cardiopulmonary bypass is closely related to systemic inflammatory reactions and oxidative stresses. Remote ischemic preconditioning is a systemic protective strategy whereby brief limb ischemia confers systemic protection against prolonged ischemia and inflammatory reactions in distant organs. This study investigated whether remote ischemic preconditioning provides systemic protective effect on kidneys that are not directly exposed to ischemia-reperfusion injury during complex valvular heart surgery. Seventy-six adult patients undergoing complex valvular heart surgery were randomly assigned to either remote ischemic preconditioning group (n = 38) or control group (n = 38). Remote ischemic preconditioning consisted of 3 10-minute cycles of lower limb ischemia and reperfusion with an automated cuff inflator. Primary end points were comparisons of biomarkers of renal injury including serum creatinine, cystatin C and neutrophil gelatinase-associated lipocalin, and incidence of acute kidney injury. Secondary end points were comparisons of myocardial enzyme release and pulmonary parameters. There were no significant differences in serum levels of biomarkers of renal injury between groups throughout the study period. The incidence of acute kidney injury did not differ between groups. Creatine kinase isoenzyme MB at 24 hours after surgery was lower, and intensive care unit stay was shorter in the remote ischemic preconditioning group than in the control group. In patients undergoing complex valvular heart surgery, remote ischemic preconditioning did not reduce degree of renal injury or incidence of acute kidney injury whereas it did reduce myocardial injury and intensive care unit stay. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  15. A Double Blind Randomized Clinical Trial of Remote Ischemic Conditioning in Live Donor Renal Transplantation.

    Science.gov (United States)

    Nicholson, Michael L; Pattenden, Clare J; Barlow, Adam D; Hunter, James P; Lee, Gwyn; Hosgood, Sarah A

    2015-08-01

    Ischemic conditioning involves the delivery of short cycles of reversible ischemic injury in order to induce protection against subsequent more prolonged ischemia. This randomized controlled trial was designed to determine the safety and efficacy of remote ischemic conditioning (RC) in live donor kidney transplantation.This prospective randomized clinical trial, 80 patients undergoing live donor kidney transplantation were randomly assigned in a 1:1 ratio to either RC or to a control group. RC consisted of cycles of lower limb ischemia induced by an arterial tourniquet cuff placed around the patient's thigh. In the RC treatment group, the cuff was inflated to 200 mm Hg or systolic pressure +25 mm Hg for 4 cycles of 5 min ischemia followed by 5 min reperfusion. In the control group, the blood pressure cuff was inflated to 25 mm Hg. Patients and medical staff were blinded to treatment allocation. The primary end-point was renal function measured by estimated glomerular filtration rate (eGFR) at 1 and 3 months posttransplant.Donor and recipient demographics were similar in both groups (P protocol described here, did not improve renal function after live donor kidney transplantation.

  16. Reperfusion Therapies for Acute Ischemic Stroke: An Update

    Science.gov (United States)

    Dorado, Laura; Millán, Mònica; Dávalos, Antoni

    2014-01-01

    Acute ischemic stroke is a major cause of morbidity and mortality in developed countries. Intravenous thrombolysis with tissue plasminogen activator (tPA) within 4.5 hours of symptoms onset significantly improves clinical outcomes in patients with acute ischemic stroke. This narrow window for treatment leads to a small proportion of eligible patients to be treated. Intravenous or intra-arterial trials, combined intravenous/intra-arterial trials, and newer devices to mechanically remove the clot from intracranial arteries have been investigated or are currently being explored to increase patient eligibility and to improve arterial recanalization and clinical outcome. New retrievable stent-based devices offer higher revascularization rates with shorter time to recanalization and are now generally preferred to first generation thrombectomy devices such as Merci Retriever or Penumbra System. These devices have been shown to be effective for opening up occluded vessels in the brain but its efficacy for improving outcomes in patients with acute stroke has not yet been demonstrated in a randomized clinical trial. We summarize the results of the major systemic thrombolytic trials and the latest trials employing different endovascular approaches to ischemic stroke. PMID:24646159

  17. A novel neuroprotective strategy for ischemic stroke: transient mild acidosis treatment by CO2 inhalation at reperfusion

    Science.gov (United States)

    Fan, Yan-Ying; Shen, Zhe; He, Ping; Jiang, Lei; Hou, Wei-wei; Shen, Yao; Zhang, Xiang-Nan; Hu, Wei-Wei; Chen, Zhong

    2014-01-01

    Acidosis is one of the key components in cerebral ischemic postconditioning that has emerged recently as an endogenous strategy for neuroprotection. We set out to test whether acidosis treatment at reperfusion can protect against cerebral ischemia/reperfusion injury. Adult male C57BL/6 J mice were subjected to 60-minute middle cerebral arterial occlusion followed by 24-hour reperfusion. Acidosis treatment by inhaling 10%, 20%, or 30% CO2 for 5 or 10 minutes at 5, 50, or 100 minutes after reperfusion was applied. Our results showed that inhaling 20% CO2 for 5 minutes at 5 minutes after reperfusion-induced optimal neuroprotection, as revealed by reduced infarct volume. Attenuating brain acidosis with NaHCO3 significantly compromised the acidosis or ischemic postconditioning-induced neuroprotection. Consistently, both acidosis-treated primary cultured cortical neurons and acute corticostriatal slices were more resistant to oxygen–glucose deprivation/reperfusion insult. In addition, acidosis inhibited ischemia/reperfusion-induced apoptosis, caspase-3 expression, cytochrome c release to cytoplasm, and mitochondrial permeability transition pore (mPTP) opening. The neuroprotection of acidosis was inhibited by the mPTP opener atractyloside both in vivo and in vitro. Taken together, these findings indicate that transient mild acidosis treatment at reperfusion protects against cerebral ischemia/reperfusion injury. This neuroprotection is likely achieved, at least partly, by inhibiting mPTP opening and mitochondria-dependent apoptosis. PMID:24192637

  18. The effect of Euryale ferox (Makhana), an herb of aquatic origin, on myocardial ischemic reperfusion injury.

    Science.gov (United States)

    Das, Samarjit; Der, Peter; Raychaudhuri, Utpal; Maulik, Nilanjana; Das, Dipak K

    2006-09-01

    Fox nut or gorgon nut (Euryale ferox--Family Nymphaeaceae), popularly known as Makhana, has been widely used in traditional oriental medicine to cure a variety of diseases including kidney problems, chronic diarrhea, excessive leucorrhea and hypofunction of the spleen. Based on the recent studies revealing antioxidant activities of Euryale ferox and its glucosides composition, we sought to determine if Euryale ferox seeds (Makhana) could reduce myocardial ischemic reperfusion injury. Two different models were used: acute model, where isolated rat hearts were preperfused for 15 min with Krebs Henseleit bicarbonate (KHB) buffer containing three different doses of makhana (25, 125 or 250 microg/ml) followed by 30 min of ischemia and 2 h of reperfusion; and chronic model, where rats were given two different doses of makhana (250 and 500 mg/kg/day) for 21 days, after which isolated hearts were subjected to 30 min of ischemia followed by 2 h of reperfusion. In both cases, the hearts of the Makhana treated rats were resistant to ischemic reperfusion injury as evidenced by their improved post-ischemic ventricular function and reduced myocardial infarct size. Antibody array technique was used to identify the cardioprotective proteins. The Makhana-treated hearts had increased amounts of thioredoxin-1 (Trx-1) and thioredoxin-related protein-32 (TRP32) compared to the control hearts. Western blot analysis confirmed increased expression of TRP32 and thioredoxin proteins. In vitro studies revealed that Makhana extracts had potent reactive oxygen species scavenging activities. Taken together, the results of this study demonstrate cardioprotective properties of Makhana and suggest that such cardioprotective properties may be linked with the ability of makhana to induce TRP32 and Trx-1 proteins and to scavenge ROS.

  19. Olmesartan restores the protective effect of remote ischemic perconditioning against myocardial ischemia/reperfusion injury in spontaneously hypertensive rats.

    Science.gov (United States)

    Lu, Xin; Bi, Yan-Wen; Chen, Ke-Biao

    2015-07-01

    Remote ischemic perconditioning is the newest technique used to lessen ischemia/reperfusion injury. However, its effect in hypertensive animals has not been investigated. This study aimed to examine the effect of remote ischemic perconditioning in spontaneously hypertensive rats and determine whether chronic treatment with Olmesartan could influence the effect of remote ischemic perconditioning. Sixty rats were randomly divided into six groups: vehicle-sham, vehicle-ischemia/reperfusion injury, vehicle-remote ischemic perconditioning, olmesartan-sham, olmesartan-ischemia/reperfusion and olmesartan-remote ischemic perconditioning. The left ventricular mass index, creatine kinase concentration, infarct size, arrhythmia scores, HIF-1α mRNA expression, miR-21 expression and miR-210 expression were measured. Olmesartan significantly reduced the left ventricular mass index, decreased the creatine kinase concentration, limited the infarct size and reduced the arrhythmia score. The infarct size, creatine kinase concentration and arrhythmia score during reperfusion were similar for the vehicle-ischemia/reperfusion group and vehicle-remote ischemic perconditioning group. However, these values were significantly decreased in the olmesartan-remote ischemic perconditioning group compared to the olmesartan-ischemia/reperfusion injury group. HIF-1α, miR-21 and miR-210 expression were markedly down-regulated in the Olmesartan-sham group compared to the vehicle-sham group and significantly up-regulated in the olmesartan-remote ischemic perconditioning group compared to the olmesartan-ischemia/reperfusion injury group. The results indicate that (1) the protective effect of remote ischemic perconditioning is lost in vehicle-treated rats and that chronic treatment with Olmesartan restores the protective effect of remote ischemic perconditioning; (2) chronic treatment with Olmesartan down-regulates HIF-1α, miR-21 and miR-210 expression and reduces hypertrophy, thereby limiting

  20. Olmesartan restores the protective effect of remote ischemic perconditioning against myocardial ischemia/reperfusion injury in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Xin Lu

    2015-07-01

    Full Text Available OBJECTIVES: Remote ischemic perconditioning is the newest technique used to lessen ischemia/reperfusion injury. However, its effect in hypertensive animals has not been investigated. This study aimed to examine the effect of remote ischemic perconditioning in spontaneously hypertensive rats and determine whether chronic treatment with Olmesartan could influence the effect of remote ischemic perconditioning. METHODS: Sixty rats were randomly divided into six groups: vehicle-sham, vehicle-ischemia/reperfusion injury, vehicle-remote ischemic perconditioning, olmesartan-sham, olmesartan-ischemia/reperfusion and olmesartan-remote ischemic perconditioning. The left ventricular mass index, creatine kinase concentration, infarct size, arrhythmia scores, HIF-1α mRNA expression, miR-21 expression and miR-210 expression were measured. RESULTS: Olmesartan significantly reduced the left ventricular mass index, decreased the creatine kinase concentration, limited the infarct size and reduced the arrhythmia score. The infarct size, creatine kinase concentration and arrhythmia score during reperfusion were similar for the vehicle-ischemia/reperfusion group and vehicle-remote ischemic perconditioning group. However, these values were significantly decreased in the olmesartan-remote ischemic perconditioning group compared to the olmesartan-ischemia/reperfusion injury group. HIF-1α, miR-21 and miR-210 expression were markedly down-regulated in the Olmesartan-sham group compared to the vehicle-sham group and significantly up-regulated in the olmesartan-remote ischemic perconditioning group compared to the olmesartan-ischemia/reperfusion injury group. CONCLUSION: The results indicate that (1 the protective effect of remote ischemic perconditioning is lost in vehicle-treated rats and that chronic treatment with Olmesartan restores the protective effect of remote ischemic perconditioning; (2 chronic treatment with Olmesartan down-regulates HIF-1α, miR-21 and mi

  1. Effects of L-carnitine on the contents of MPO and NO in rats with renal ischemic reperfusion injury%左卡尼汀对肾缺血再灌注损伤大鼠肾组织MPO和NO含量的影响

    Institute of Scientific and Technical Information of China (English)

    许益笑; 张睿喆; 王德选; 倪世容; 王万铁; 郑绿珍; 王丽; 熊锡山; 郭坤元

    2012-01-01

    Aim:To investigate possible mechanisms involved in the protection of L-carnitine against renal ischemic reperfusion injury( RIRI ) in rats. Methods:A total of 48 SD healthy rats were divided into control and L-carnitine groups ( n = 24 ). Model of RIRI was established in the two groups,and 6 rats were killed at ischemic reperfusion( IR ) 0,1 ,6,and 12 h. The contents of serum urea nitrogen( BUN ) and creatinine( Cr ),the myeloperoxidase ( MPO ) and NO in nephridial tissue were measured. The pathological changes in renal tissue were observed. Results:In the two groups,Cr and BUN contents of the IR 0 ,1,6,12 h rats were obviously different F_group = 5. 116 and 6. 602, F_time = 15. 235 and 47. 118 ,P < 0. 05 ). Comparing with those of IR 0 h killed rats ,Cr and BUN contents of the IR 6 and 12 h killed rats increased significantly; Cr and BUN contents of the IR 6 and 12 h killed rats were lower in L-carnitine group than those in the control group( P < 0. 05 ). In the two groups, MPO and NO contents of the IR 0,1,6,12 h rats were obviously different( F_group = 6. 259 and 3.729,F_time =7.709 and 39.671 ,P <0.05 ). Comparing with those of IR 0 h killed rats,MPO content of the IR 12 h killed rats increased significantly in the two groups;MPO content of the IR 12 h killed rats was higher in control group than that in the L-carnitine group( P <0.05 ). In the two groups,comparing with those of IR 0 h killed rats,NO content of the IR 12 h killed rats decreased significantly; NO content of the IR 12 h killed rats was lower in control group than that in the L-carnitine group( P <0.05 ). In addition,renal histological injuries were attenuated after L-carnitine administration. Conclusion: L-carnitine protects kidney against acute RIRI through inhibiting neutrophil aggregation,lowering the release of MPO and increasing the synthesis of NO in the renal tissue.%目的:探讨左卡尼汀对肾缺血再灌注损伤(RIRI)大鼠能量代谢的影响及其机制.方法:健康SD大鼠48只

  2. [Ischemic colitis after renal transplantation:etiology and pathogenesis].

    Science.gov (United States)

    Alperovich, G; Idiarte, L; Besasso, O; Avagnina, A

    2003-01-01

    Ischemic colitis is a well-recognized complication occurring in renal transplant recipients. It has often been associated with cytomegalovirus (CMV) vasculitis. However, the diagnosis of this pathology in the absence of CMV suggests that other etiological factors might be involved. Drugs inducing mesenteric vasoconstriction, such as non-steroidal anti-inflamatory drugs (NSAIDs) and cyclosporine could be related to this entity.

  3. Proprotein convertase 1 mRNA and protein expression in ischemic rat cortex after reperfusion

    Institute of Scientific and Technical Information of China (English)

    Shuqin Zhan; An Zhou; Jingquan Lan; Tao Yang

    2011-01-01

    Proprotein convertase 1 (PC1) is a member of the family of proprotein convertases (PCs), which are the processing enzymes of neuropeptides. Previous studies have addressed PC1 effects with regard to the neuroendocrine system. In this study, the developing changes of PC1 mRNA and PC1 protein in rat cortices after transient focal cerebral ischemia were investigated by fluorescent double labeling (both in situ hybridization and immunocytochemistry) using a transient focal cerebral ischemia model in rats. The results were compared with those of sham-operated rat cortices. Both the mRNA and protein levels of PC1 in ischemic cortices decreased gradually at 4, 8, and 16 hours of reperfusion after 100 minutes of middle cerebral artery occlusion. After 24 hours of reperfusion, enhanced intensities of signals for PC1 protein were observed, while signals for PC1 mRNA remained low. These results suggest that transient focal cerebral ischemia influences PC1 mRNA and protein expression in cortices of ischemic rats. Thus, PC1 is regulated by ischemic stress.

  4. Effects of preconditioning on reperfusion arrhythmias, myocardial functions, formation of free radicals, and ion shifts in isolated ischemic/reperfused rat hearts.

    Science.gov (United States)

    Tosaki, A; Cordis, G A; Szerdahelyi, P; Engelman, R M; Das, D K

    1994-03-01

    The effects of preconditioning on development of reperfusion-induced ventricular fibrillation (VF), ventricular tachycardia (VT), free radical formation, and ion shifts, particularly those of Na, K, Ca, and Mg, were studied in isolated rat heart. Hearts were randomly divided into four groups: group I, aerobically perfused time-matched controls with no preconditioning or ischemia; group II, hearts subjected to 30-min global ischemia followed by 30-min reperfusion; group III, hearts subjected to one cycle of preconditioning, consisting of 5-min global ischemia plus 10-min reperfusion, followed by 30-min global ischemia plus 30-min reperfusion; and group IV, hearts subjected to four cycles of preconditioning (5-min ischemia plus 10-min reperfusion) followed by 30-min ischemia plus 30-min reperfusion. The incidences of VF and VT were reduced from their nonpreconditioned ischemic values of 100 and 100% in group II to 83 and 92% in group III and to 33% (p < 0.05) and 41% (p < 0.05) in group IV, respectively. Maximum malondialdehyde formation, as an indirect marker of free radicals, was observed after 30-min ischemia followed by 10-min reperfusion (0.72 +/- 0.1 nmol/ml) in the nonpreconditioned ischemic group (protocol II). One and four cycles of preconditioning reduced formation of malondialdehyde from the nonpreconditioned ischemic value of 0.72 +/- 0.1 to 0.35 +/- 0.02 and 0.26 +/- 0.02 nmol/ml (p < 0.05), respectively. The same trend was observed when free radical formation was directly detected by salicylic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Changes of Apoptosis in Rats of Acute Ischemic Renal Injury under Treatment of Tetrandrine

    Institute of Scientific and Technical Information of China (English)

    钱玲梅; 王笑云; 冷静

    2002-01-01

    ObjectiveTo elucidate the effect of tetrandrine on acute ischemic renal injury and its relation with apoptosis.MethodsA model for bilateral post-ischemic renal injury in rats was developed by clamping renal pedicles for 45 min.Renal tissular DNA fragmentation analysis and renal tissular HE staining were used.Also quantitative analysis of apoptosis in injured renal tubular epithelium was carried out by using TdT-mediated dUTP nick and labeling (TUNEL).ResultsApoptosis of renal tubular epithelium increased in acute ischemic renal injury.Tetrandrine could remarkably decrease the level of apoptosis in injured renal tubule while protecting renal tissue against the ischemic injuries.ConclusionTetrandrine could adjust the level of apoptosis in renal tubular epithelium and alleviate renal tissular injury.``

  6. Changes of Apoptosis in Rats of Acute Ischemic Renal Injury under Treatment of Tetrandrine

    Institute of Scientific and Technical Information of China (English)

    钱玲梅; 王笑云; 等

    2002-01-01

    Objective To elucidate the effect of tetrandrine on acute ischemic renal injury and its relation with apoptosis.Methods A model for bilateral post-ischemic renal injury in rats was developed by clamping renal pedicles for 45 min.Renal tissular DNA fragmentation analysis and renal tissular HE staining were used.Also quantitative analysis of apoptosis in injured renal tubular epithelium was carried out by using TdT-mediated dUTP nick and labeling(TUNEL).Results Apoptosis of renal tubular epithelium increased in acute ischemic renal injury.Tetrandrine could remarkably decrease the level of apoptosis in injured renal tubule while protecting renal tissue against the ischemic injuries.Conclusion Tetrandrine could adjust the level of apoptosis in renal tubular epithelium and alleviate renal tissular injury.

  7. Retention and clearance of C-11 palmitic acid in ischemic and reperfused canine myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Schwaiger, M.; Schelbert, H.R.; Keen, R.; Vinten-Johansen, J.; Hansen, H.; Selin, C.; Barrio, J.; Huang, S.C.; Phelps, M.E.

    1985-08-01

    Free fatty acids are the major energy source for cardiac muscle. Oxidation of fatty acid decreases or even ceases during ischemia. Its recovery after transient ischemia remains largely unexplored. Using intracoronary carbon-11 palmitic acid as a tracer of myocardial fatty acid metabolism in an open chest dog model, retention and clearance of tracer in myocardium were evaluated at control, during ischemia and after reperfusion following a 20 minute occlusion of the left anterior descending coronary artery. Myocardial C-11 time-activity curves were analyzed with biexponential curve-fitting routines yielding fractional distribution and clearance half-times of C-11 palmitic acid in myocardial tissue. In animals with permanent occlusion and intracoronary injection of C-11 palmitic acid distal to the occlusion site, the relative size and half-time of the early clearance curve component differed markedly from control values and did not change with ongoing ischemia. Conversely, in animals with only 20 minutes of coronary occlusion, the relative size of the early C-11 clearance phase was still significantly depressed at 20 and 90 minutes of reperfusion but returned to control level at 180 minutes. Tissue C-11 clearance half-times remained significantly prolonged throughout the reperfusion period. Regional function in reperfused myocardium monitored with ultrasonic crystals recovered slowly and was still less than control after 3 hours of reperfusion. The data indicate that after transient ischemia, myocardial fatty acid metabolism fails to recover immediately. Because the metabolic recovery occurs in parallel with recovery of regional function, C-11 palmitic acid in conjunction with positron tomography may be useful for studying regional fatty acid metabolism noninvasively after an ischemic injury, and may be helpful in identifying reversible tissue injury.

  8. Mechanisms of selective head cooling for resuscitating damaged neurons during post-ischemic reperfusion

    Institute of Scientific and Technical Information of China (English)

    段满林; 李德馨; 徐建国

    2002-01-01

    Objective To evaluate the efficacy and the mechanism of application of selective head cooling on neuronal morphological damage during postischemic reperfusion in a rabbit model. Methods 168 New Zealand rabbits were randomized into three groups. Group Ⅰ [n=24, (38±0.5)℃, non-ischemic control]; Group Ⅱ [n=72, (38±0.5)℃, normothermic reperfusion]; Group Ⅲ [n=72, (28±0.5)℃, selective head cooling, initiated at the beginning of reperfusion). Animals in three subgroups (n=24, each) of Group Ⅱ and Group Ⅲ had reperfused lasting for 30, 180 and 360 min respectively. Using computerized image analysis technique on morphological changes of nucleus, the degree of neuronal damage in 12 regions were differentiated into type A (normal), type B (mild damaged), type C (severely damaged) and type D (necrotic). Fourteen biochemical parameters in brain tissues were measured. Results As compared with Group Ⅰ, the counts of type A neuron decreased progressively, and those of type B, C and D increased significantly in Group Ⅱ during reperfusion (P<0.01). In Group Ⅱ, vasoactive intestinal peptide, b-endorphine, prostacyclin, T3 and Na+, K+-ATPase were correlated with the changes of type A; b-endorphine and thromboxane with type B; glucose and vasopressin with type C; Na+, K+-ATPase, glutamic acid, T3 and vasoactive intestinal peptide with type D (P<0.05). As compared with Group Ⅱ, the counts of type A increased, and those of type C and D significantly decreased in Group Ⅲ (P<0.01). In Group Ⅲ, Ca2+, Mg2+-ATPase were correlated with the changes of type A, C and D (P<0.01). Conclusion Selective head cooling for sex hours during postischemic reperfusion does improve neuronal morphological outcomes in terms of morphological changes.

  9. mTORC1 maintains renal tubular homeostasis and is essential in response to ischemic stress.

    Science.gov (United States)

    Grahammer, Florian; Haenisch, Nora; Steinhardt, Frederic; Sandner, Lukas; Sander, Lukas; Roerden, Malte; Arnold, Frederic; Cordts, Tomke; Wanner, Nicola; Reichardt, Wilfried; Kerjaschki, Dontscho; Ruegg, Markus A; Hall, Michael N; Moulin, Pierre; Busch, Hauke; Boerries, Melanie; Walz, Gerd; Artunc, Ferruh; Huber, Tobias B

    2014-07-08

    Mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of cell metabolism and autophagy. Despite widespread clinical use of mTORC1 inhibitors, the role of mTORC1 in renal tubular function and kidney homeostasis remains elusive. By using constitutive and inducible deletion of conditional Raptor alleles in renal tubular epithelial cells, we discovered that mTORC1 deficiency caused a marked concentrating defect, loss of tubular cells, and slowly progressive renal fibrosis. Transcriptional profiling revealed that mTORC1 maintains renal tubular homeostasis by controlling mitochondrial metabolism and biogenesis as well as transcellular transport processes involved in countercurrent multiplication and urine concentration. Although mTORC2 partially compensated for the loss of mTORC1, exposure to ischemia and reperfusion injury exaggerated the tubular damage in mTORC1-deficient mice and caused pronounced apoptosis, diminished proliferation rates, and delayed recovery. These findings identify mTORC1 as an important regulator of tubular energy metabolism and as a crucial component of ischemic stress responses.

  10. Renoprotective capacities of non-erythropoietic EPO derivative, ARA290, following renal ischemia/reperfusion injury

    NARCIS (Netherlands)

    van Rijt, Willem G; Nieuwenhuijs-Moeke, Gertrude J; van Goor, Harry; Ottens, Petra J; Ploeg, Rutger J; Leuvenink, Henri G D

    2013-01-01

    Background: ARA290 is a non-erythropoietic EPO derivative which only binds to the cytoprotective receptor complex (EPOR2-beta cR(2)) consisting of two EPO-receptors (EPOR) and two beta common receptors (beta cR). ARA290 is renoprotective in renal ischemia/reperfusion (I/R). In a renal I/R model we f

  11. Ischemia-Reperfusion Injury and Ischemic-Type Biliary Lesions following Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Raffaele Cursio

    2012-01-01

    Full Text Available Ischemia-reperfusion (I-R injury after liver transplantation (LT induces intra- and/or extrahepatic nonanastomotic ischemic-type biliary lesions (ITBLs. Subsequent bile duct stricture is a significant cause of morbidity and even mortality in patients who underwent LT. Although the pathogenesis of ITBLs is multifactorial, there are three main interconnected mechanisms responsible for their formation: cold and warm I-R injury, injury induced by cytotoxic bile salts, and immunological-mediated injury. Cold and warm ischemic insult can induce direct injury to the cholangiocytes and/or damage to the arterioles of the peribiliary vascular plexus, which in turn leads to apoptosis and necrosis of the cholangiocytes. Liver grafts from suboptimal or extended-criteria donors are more susceptible to cold and warm I-R injury and develop more easily ITBLs than normal livers. This paper, focusing on liver I-R injury, reviews the risk factors and mechanisms leading to ITBLs following LT.

  12. Conditioning techniques and ischemic reperfusion injury in relation to on-pump cardiac surgery

    DEFF Research Database (Denmark)

    Holmberg, Fredrik Eric Olof; Ottas, Konstantin Alex; Andreasen, Charlotte

    2014-01-01

    OBJECTIVES: The objective was to investigate the potential protective effects of two conditioning methods, on myocardial ischemic and reperfusion injury in relation to cardiac surgery. DESIGN: Totally 68 patients were randomly assigned to either a control group (n = 23), a remote ischemic....... The other secondary endpoints were metabolic parameters related to myocardial ischemia, measured using microdialysis technique, as well as other operative- and postoperative data. RESULTS: Postoperative cardiac enzyme release indicated a possible beneficial effect of the interventions, but the difference......, unable to show distinct protective effects of the studied conditioning methods. However, this trial can hopefully contribute to generate a productive discussion concerning limitations and future use of cardiac conditioning as well as microdialysis technique....

  13. Nifedipine does not affect free radical induced lipid peroxidation following renal allograft reperfusion.

    Science.gov (United States)

    Davenport, A; Hopton, M; Bolton, C

    1994-01-01

    We prospectively measured lipid peroxidation following reperfusion during 44 renal allograft transplant operations. Twenty-four (55%) recipients were taking nifedipine pre- and then postoperatively, and 20 (45%) were not. There were no differences between the groups in terms of recipient or donor status. Plasma malondialdehyde (MDA), mean 2.2 (0.2) mumol/L (SEM) vs. 1.73 (0.1) was greater in the group not prescribed nifedipine, p nifedipine group to 0.38 (0.02) at 30 min after reperfusion and 0.38 (0.03) at 60 min, p nifedipine and no-nifedipine groups, respectively. There was no difference in postoperative renal function between the groups. This study suggests that the oral administration of nifedipine may not prevent the production of lipid peroxides, as measured by changes in plasma malondialdehyde, following renal allograft reperfusion and that it does not affect renal function in the early postoperative period.

  14. Propofol attenuation of renal ischemia/reperfusion injury involves heme oxygenase-1

    Institute of Scientific and Technical Information of China (English)

    Hui-hua WANG; Hai-yan ZHOU; Cong-cong CHEN; Xiu-lai ZHANG; Gang CHENG

    2007-01-01

    Aim: To examine the protective effect of propofol in renal ischemia/reperfusion (I/R) injury and the role of heme oxygenase-1 (HO-1) in this process. Methods:-Sprague-Dawley rats were randomly divided into 3 groups: (i) sham-operated group; (ii) I/R group; and (iii) propofol group. Bilateral renal warm ischemia for 45 rain was performed. After 2, 6, and 24 h reperfusion, blood samples and kidneys were collected for assessment of renal injury, and HO-1 expressions were ana-lyzed by immunohistochemical analysis, RT-PCR and Western blotting. Results: Blood urea nitrogen and serum creatinine levels in the propofol group were sig-nificantly lower than that in the UR group at 24 h after reperfusion. The mean histological score by Paller's standard showed that propofol significantly attenu-ated renal I/R injury after 6 h reperfusion. Propofol increased HO-1 mRNA and protein levels 2 h after repeffusion, whereas HO-1 expressions were present at exceedingly low levels in the I/R group and the sham-operated group at same time point. Propofol also markedly increased HO- 1 mRNA and protein levels than I/R at 6 and 24 h after reperfusion. Conclusion: These results suggest that propofol mitigates renal I/R injury in rats. This protection may be partly through the induc-tion of the HO- 1 expression.

  15. Effect of tetramethylpyrazine on P-selectin and hepatic/renal ischemia and reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Jin-Lian Chen; Tong Zhou; Wei-Xiong Chen; Jin-Shui Zhu; Ni-Wei Chen; Ming-Jun Zhang; Yun-Lin Wu

    2003-01-01

    AIM: To investigate the effect of tetramethylpyrazine on hepatic/renal ischemia and reperfusion injury in rats.METHODS: Hepatic/renal function, histopathological changes,and hepatic/renal P-selectin expression were studied with biochemical measurement and immunohistochemistry in hepatic/renal ischemia and reperfusion injury in rat models.RESULTS: Hepatic/renal insufficiency and histopathological damage were much less in the tetramethylpyrazine-treated group than those in the saline-treated groups. Hepatic/ renal P-selectin expression was down regulated in the tetramethylpyrazine-treated group.CONCLUSION: P-selectin might mediate neutrophil infiltration and contribute to hepatic/renal ischemia and reperfusion injury. Tetramethylpyrazine might prevent hepatic/renal damage induced by ischemia and reperfusion injury through inhibition of P-selectin.

  16. Is acute reperfusion therapy safe in acute ischemic stroke patients who harbor unruptured intracranial aneurysm?

    Science.gov (United States)

    Mowla, Ashkan; Singh, Karanbir; Mehla, Sandhya; Ahmed, Mohammad K; Shirani, Peyman; Kamal, Haris; Krishna, Chandan; Sawyer, Robert N; Ching, Marilou; Siddiqui, Adnan H; Levy, Elad I; Snyder, Kenneth V; Crumlish, Annemarie; Hopkins, L N

    2015-10-01

    Intracranial aneurysms are currently considered as contraindication for intravenous thrombolysis in acute ischemic stroke, very likely due to a possible increase in the risk of bleeding from aneurysm rupture; however, there is limited data available on whether intravenous thrombolysis is safe for acute ischemic stroke patients with pre-existing intracranial aneurysms. To find out the safety of intravenous thrombolysis in acute ischemic stroke patients who harbor unruptured intracranial aneurysms. We retrospectively reviewed the medical records and cerebrovascular images of all the patients treated with intravenous thrombolysis for acute ischemic stroke in our center from the beginning of 2006 till the end of April 2014. Those with unruptured intracranial aneurysm present on cerebrovascular images prior to acute reperfusion therapy were identified. Post-thrombolysis brain imaging was reviewed to evaluate for any intraparenchymal or subarachnoid hemorrhage related or unrelated to the aneurysm. A total of 637 patients received intravenous thrombolysis for acute ischemic stroke in our center during an 8·3-year period. Thirty-three (5·2%) were found to have at least one intracranial aneurysms. Twenty-three (70%) of those received only intravenous thrombolysis, and 10 patients received combination of intravenous and intra-arterial thrombolysis. The size of the largest aneurysm was 10 mm in maximum diameter (range: 2-10 mm). The mean size of aneurysms was 4·8 mm. No symptomatic intracranial hemorrhage occurred among the 23 patients receiving only intravenous thrombolysis. Out of those who received a combination of intravenous and intra-arterial thrombolysis, one developed symptomatic intracranial hemorrhage in the location of acute infarct, distant to the aneurysm location. Our findings suggest that neither intravenous thrombolysis nor combination of intravenous and intra-arterial thrombolysis increases the risk of aneurysmal hemorrhage in acute ischemic stroke

  17. Protective effect of nitric oxide induced by ischemic preconditioning on reperfusion injury of rat liver graft

    Institute of Scientific and Technical Information of China (English)

    Jian-Ping Gong; Bing Tu; Wei Wang; Yong Peng; Shou-Bai Li; Lu-Nan Yan

    2004-01-01

    AIM: Ischemic preconditioning (IP) is a brief ischemic episode,which confers a state of protection against the subsequent long-term ischemia-reperfusion injuries. However, little is known regarding the use of IP before the sustained cold storage and liver transplantation. The present study was designed to evaluate the protective effect of IP on the long-term preservation of liver graft and the prolonged anhepatic-phase injury.METHODS: Male Sprague-Dawley rats were used as donors and recipients of orthotopic liver transplantation. All livers underwent 10 min of ischemia followed by 10 min of reperfusion before harvest. Rat liver transplantation was performed with the portal vein clamped for 25 min. Tolerance of transplanted liver to the reperfusion injury and liverdamage were investigated. The changes in adenosineconcentration in hepatic tissue and those of nitric oxide (NO)and tumor necrosis factor (TNF) in serum were also assessed.RESULTS: Recipients with IP significantly improved theirone-week survival rate and liver function, they had increasedlevels of circulating NO and hepatic adenosine, and a reducedlevel of serum TNF, as compared to controls. Histologicalchanges indicating hepatic injuries appeared improved in theIP group compared with those in control group. The protectiveeffect of IP was also obtained by administration of adenosine,while blockage of the NO pathway using Nω-nitro-L-argininemethyl ester abolished the protective effect of IRCONCLUSION: IP appears to have a protective effect onthe long-term preservation of liver graft and the prolongedanhepatic-phase injuries. NO may be involved in this process.

  18. The protective activity of noscapine on renal ischemia–reperfusion injury in male Wistar rat

    Science.gov (United States)

    Khanmoradi, Mehrangiz; Ali Mard, Seyyed; Aboutaleb, Nahid; Nobakht, Malihe; Mahmoudian, Masoud

    2014-01-01

    Objective(s): Bradykinin is a part of the kinin-kallikrein system which is involved in ischemia-reperfusion injury via B1 and B2 receptors. Noscapine is a non-competitive antagonist of bradykinin receptors. Noscapine has been reported to to be able to protect some organs against ischemia-reperfusion injury but its effect on renal ischemia-reperfusion injury (RIR) in rats is unknown. Therefore, the present study was designed to evaluate the effect of noscapine on renal ischemia-reperfusion injury in rats. Materials and Methods: Twenty four rats were randomly assigned to four groups; sham, RIR control, pre-and post-treatment with noscapine. To induce RIR injury, 20 days after right nephrectomy, animals underwent a midline laparotomy and the renal artery was clamped for 40 min to induce ischemia, and the clamp was then removed to allow reperfusion for 48 hr. Animals received noscapine or vehicle 1 hr before RIR or just prior to reperfusion. At the end of the experiment, animals were killed by cardiac exsanguination. Blood samples were collected to assess blood urea nitrogen (BUN) and creatinine. The kidneys were also removed for histopathlogical and western-blot analysis. Results: Noscapine treatment 1 hr before RIR or just prior to reperfusion protects the renal tissue structure as compared with the control. The expression levels of the studied inflammatory mediators, TNF-α and MCP-1in pretreated-, and treated-noscapine groups decreased as compared with the control group. The levels of BUN and creatinine in pre-, and post-treated noscapine groups were significantly lower than in control animals. Conclusion: Noscapine protects renal tissue structure and function against RIR through down-regulation of the inflammatory mediators. PMID:24904716

  19. Protective effect of bradykinin antagonist Hoe-140 during in vivo myocardial ischemic-reperfusion injury in the cat.

    Science.gov (United States)

    Kumari, Rashmi; Maulik, Mohua; Manchanda, Subhash Chandra; Maulik, Subir Kumar

    2003-10-15

    The effect of icatibant (Hoe-140), a selective bradykinin receptor (B(2)) antagonist on myocardial ischemic-reperfusion injury was studied in open chest barbiturate anaesthetized cats. The left anterior descending coronary artery was occluded for 15 min, followed by 60 min of reperfusion. Saline or icatibant (200 microg/kg) was administered intravenously slowly over 2 min, 5 min before reperfusion. In the saline-treated group, myocardial ischemic-reperfusion injury was evidenced by depressed MAP, depressed peak positive and negative dP/dt and elevated left ventricular end-diastolic pressure and enhanced oxidative stress [elevated plasma thiobarbituric acid reactive substances (TBARS; a marker for lipid peroxidation), depressed myocardial GSH (reduced glutathione), superoxide dismutase (SOD), catalase] and depletion of adenosine triphosphate (ATP) along with rise in plasma creatine phosphokinase (CPK). Administration of icatibant resulted in complete hemodynamic recovery together with repletion of ATP and reduction in plasma TBARS without any significant change in myocardial SOD, catalase and GSH. The results of the present study suggest a protective role of icatibant in myocardial ischemic-reperfusion injury.

  20. Multiparametric Magnetic Resonance Imaging for Prediction of Parenchymal Hemorrhage in Acute Ischemic Stroke After Reperfusion Therapy.

    Science.gov (United States)

    Nael, Kambiz; Knitter, James R; Jahan, Reza; Gornbein, Jeffery; Ajani, Zahra; Feng, Lei; Meyer, Brett C; Schwamm, Lee H; Yoo, Albert J; Marshall, Randolph S; Meyers, Philip M; Yavagal, Dileep R; Wintermark, Max; Liebeskind, David S; Guzy, Judy; Starkman, Sidney; Saver, Jeffrey L; Kidwell, Chelsea S

    2017-03-01

    Patients with acute ischemic stroke are at increased risk of developing parenchymal hemorrhage (PH), particularly in the setting of reperfusion therapies. We have developed a predictive model to examine the risk of PH using combined magnetic resonance perfusion and diffusion parameters, including cerebral blood volume (CBV), apparent diffusion coefficient, and microvascular permeability (K2). Voxel-based values of CBV, K2, and apparent diffusion coefficient from the ischemic core were obtained using pretreatment magnetic resonance imaging data from patients enrolled in the MR RESCUE clinical trial (Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy). The associations between PH and extreme values of imaging parameters were assessed in univariate and multivariate analyses. Receiver-operating characteristic curve analysis was performed to determine the optimal parameter(s) and threshold for predicting PH. In 83 patients included in this analysis, 20 developed PH. Univariate analysis showed significantly lower 10th percentile CBV and 10th percentile apparent diffusion coefficient values and significantly higher 90th percentile K2 values within the infarction core of patients with PH. Using classification tree analysis, the 10th percentile CBV at threshold of 0.47 and 90th percentile K2 at threshold of 0.28 resulted in overall predictive accuracy of 88.7%, sensitivity of 90.0%, and specificity of 87.3%, which was superior to any individual or combination of other classifiers. Our results suggest that combined 10th percentile CBV and 90th percentile K2 is an independent predictor of PH in patients with acute ischemic stroke with diagnostic accuracy superior to individual classifiers alone. This approach may allow risk stratification for patients undergoing reperfusion therapies. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00389467. © 2017 The Authors.

  1. Acute ischemia/reperfusion injury after isogeneic kidney transplantation is mitigated in a rat model of chronic renal failure.

    Science.gov (United States)

    Vercauteren, Sven R; Ysebaert, Dirk K; Van Rompay, An R; De Greef, Kathleen E; De Broe, Marc E

    2003-05-01

    The influence of chronic renal failure on renal susceptibility to an acute ischemic insult was evaluated. Recipient Lewis rats were randomly assigned to undergo 5/6 nephrectomy (chronic renal failure, CRF) or sham operation (normal renal function, NRF). After 11 weeks, normal kidneys of Lewis donor rats were transplanted in the recipients. The outcome of the isografts was assessed. Filtration capacity of the isografts in the CRF rats was preserved to approximately one-quarter of its normal capacity on the 1st day post-transplantation, whereas it fell to 0 in the NRF rats. This was reflected by a significantly higher increase in serum creatinine in the latter group. The isografts in the CRF rats had a significantly lower degree of acute tubular necrosis and no increase in the number of macrophages and T lymphocytes in the first 24 h in contrast to the NRF rats. Epithelial regeneration and repair started earlier in the CRF group. In conclusion, the present study indicated that CRF blunted ischemia/reperfusion injury of a transplanted kidney, and that its regeneration capacity was certainly not hampered by the presence of chronic uremia. These results will be the basis for studies on modulation of early leukocyte-endothelial interactions resulting from immunological disturbances inherent to the uremic environment.

  2. The protective effect of erythropoietin pretreatment on ischemic acute renal failure in rats

    Directory of Open Access Journals (Sweden)

    Jing-Guang Liao

    2016-09-01

    Full Text Available Objective: To investigate the protective effect of erythropoietin (EPO pretreatment on ischemic acute renal failure in rats and its molecular mechanism. Methods: Male Sprague–Dawley rats were selected as experimental animals and they were randomly divided into the sham operation group (sham group, ischemia-reperfusion injury group (IRI group and EPO pretreatment group (EPO group. Each group had 15 rats. Serum specimens and renal specimens were collected after a IRI model was built for 4, 12 and 24 h. The contents of creatinine, urea nitrogen tumor necrosis factor-alpha (TNF-a, interleukin-1 (IL-1, IL-6 and IL-8 in serum and the contents of TNF-a, IL- 1, IL-6, IL-8, toll like receptor 4 (TLR4 and nuclear factor-kappa B (NF-kB in the kidney tissue were determined. Results: After 4, 12 and 24 h reperfusion, there were differences between the contents of creatinine, urea nitrogen TNF-a, IL-1, IL-6 and IL-8 in serum and the contents of TNF-a, IL-1, IL-6, IL-8, TLR4 and NF-kB in rats of the three groups (P < 0.05. The contents of creatinine, urea nitrogen TNF-a, IL-1, IL-6 and IL-8 in serum and the contents of TNF-a, IL-1, IL-6, IL-8, TLR4 and NF-kB in the kidney tissue in rats of the IRI group were significantly higher than those of the sham group; and the contents of creatinine, urea nitrogen TNF-a, IL-1, IL-6 and IL-8 in serum and the contents of TNF-a, IL-1, IL-6, IL- 8, TLR4 and NF-kB in the kidney tissue in rats of the EPO group were distinctly lower than those of the IRI group. Conclusions: EPO pretreatment can protect the renal function of rats with ischemic acute renal failure by inhibiting the TLR4/NF-kB pathway mediated inflammatory responses.

  3. Gender difference and sex hormone production in rodent renal ischemia reperfusion injury and repair

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    Ghazali Daniel

    2011-06-01

    Full Text Available Abstract Background Several lines of evidence suggest a protective effect of female sex hormones in several organs subjected to ischemia-reperfusion injury. The aim of the study was to investigate sex hormone production in male rats after a renal ischemia-reperfusion sequence and analyze the influence of gender differences on tissue remodelling during the recovery process. Method Age-matched sexually mature male and female rats were subjected to 60 min of renal unilateral ischemia by pedicle clamping with contralateral nephrectomy and followed for 1 or 5 days after reperfusion. Plasma creatinine, systemic testosterone, progesterone and estradiol levels were determined. Tubular injury, cell proliferation and inflammation, were evaluated as well as proliferating cell nuclear antigen, vimentin and translocator protein (TSPO expressions by immunohistochemistry. Results After 1 and 5 days of reperfusion, plasma creatinine was significantly higher in males than in females, supporting the high mortality in this group. After reperfusion, plasma testosterone levels decreased whereas estradiol significantly increased in male rats. Alterations of renal function, associated with tubular injury and inflammation persisted during the 5 days post-ischemia-reperfusion, and a significant improvement was observed in females at 5 days of reperfusion. Proliferating cell nuclear antigen and vimentin expression were upregulated in kidneys from males and attenuated in females, in parallel to injury development. TSPO expression was transiently increased in proximal tubules in male rats. Conclusions After ischemia, renal function recovery and tissue injury is gender-dependent. These differences are associated with a modulation of sex hormone production and a modification of tissue remodeling and proliferative cell processes.

  4. Expression of Bcl-2 and NF-κB in brain tissue after acute renal ischemia-reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Na Zhang; Gen-Yang Cheng; Xian-Zhi Liu; Feng-Jiang Zhang

    2014-01-01

    Objective:To investigate the effect of acute renal ischemia reperfusion on brain tissue. Methods:Fourty eight rats were randomly divided into four groups(n=12): sham operation group,30 min ischemia60 min reperfusion group,60 min ischemia60 min reperfusion group, and 120 min ischemia60 min reperfusion group.The brain tissues were taken after the experiment. TUNEL assay was used to detect the brain cell apoptosis, and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors.Results:Renal ischemia-reperfusion induced apoptosis of brain tissues, and the apoptosis increased with prolongation of ischemia time.The detection at the molecular level showed decreasedBcl-2 expression, increasedBax expression, upregulated expression ofNF-κB and its downstream factor COX-2/PGE2.Conclusions:Acute renal ischemia-reperfusion can cause brain tissue damage, manifested as induced brain tissues apoptosis and inflammation activation.

  5. σ1-Receptor Agonism Protects against Renal Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Hosszu, Adam; Antal, Zsuzsanna; Lenart, Lilla; Hodrea, Judit; Koszegi, Sandor; Balogh, Dora B; Banki, Nora F; Wagner, Laszlo; Denes, Adam; Hamar, Peter; Degrell, Peter; Vannay, Adam; Szabo, Attila J; Fekete, Andrea

    2017-01-01

    Mechanisms of renal ischemia-reperfusion injury remain unresolved, and effective therapies are lacking. We previously showed that dehydroepiandrosterone protects against renal ischemia-reperfusion injury in male rats. Here, we investigated the potential role of σ1-receptor activation in mediating this protection. In rats, pretreatment with either dehydroepiandrosterone or fluvoxamine, a high-affinity σ1-receptor agonist, improved survival, renal function and structure, and the inflammatory response after sublethal renal ischemia-reperfusion injury. In human proximal tubular epithelial cells, stimulation by fluvoxamine or oxidative stress caused the σ1-receptor to translocate from the endoplasmic reticulum to the cytosol and nucleus. Fluvoxamine stimulation in these cells also activated nitric oxide production that was blocked by σ1-receptor knockdown or Akt inhibition. Similarly, in the postischemic rat kidney, σ1-receptor activation by fluvoxamine triggered the Akt-nitric oxide synthase signaling pathway, resulting in time- and isoform-specific endothelial and neuronal nitric oxide synthase activation and nitric oxide production. Concurrently, intravital two-photon imaging revealed prompt peritubular vasodilation after fluvoxamine treatment, which was blocked by the σ1-receptor antagonist or various nitric oxide synthase blockers. In conclusion, in this rat model of ischemia-reperfusion injury, σ1-receptor agonists improved postischemic survival and renal function via activation of Akt-mediated nitric oxide signaling in the kidney. Thus, σ1-receptor activation might provide a therapeutic option for renoprotective therapy.

  6. Role of mitochondria in cell apoptosis during hepatic ischemia-reperfusion injury and protective effect of ischemic postconditioning

    Institute of Scientific and Technical Information of China (English)

    Kai Sun; Zhi-Su Liu; Quan Sun

    2004-01-01

    AIM: To investigate the role of mitochondria in cell apoptosis during hepatic ischemia-reperfusion injury and protective effect of ischemic postconditioning (IPC).METHODS: A rat model of acute hepatic ischemia-reperfusion was established, 24 healthy male Wistar rats were randomly divided into sham-operated group, ischemia-reperfusion group (IR) and IPC group. IPC was achieved by several brief pre-reperfusions followed by a persistent reperfusion.Concentration of malondialdehyde (MDA) and activity of several antioxidant enzymes in hepatic tissue were measured respectively. Apoptotic cells were detected by TdT-mediated dUTP-biotin nick end labeling (TUNEL) and expression of Bcl-2 protein was measured by immunohistochemical techniques. Moreover, mitochondrial ultrastructure and parameters of morphology of the above groups were observed by electron microscope.RESULTS: Compared with IR group, the concentration of MDA and the hepatocellular apoptotic index in IPC group was significantly reduced (P<0.05), while the activity of antioxidant enzymes and OD value of Bcl-2 protein were markedly enhanced (P<0.05). Moreover, the injury of mitochondrial ultrastructure in IPC group was also obviously relieved.CONCLUSION: IPC can depress the synthesis of oxygen free radicals to protect the mitochondrial ultrastructure and increase the expression of Bcl-2 protein that lies across the mitochondrial membrane. Consequently, IPC can reduce hepatocellular apoptosis after reperfusion and has a protective effect on hepatic ischemia-reperfusion injury.

  7. Physiologically tolerable insulin reduces myocardial injury and improves cardiac functional recovery in myocardial ischemic/reperfused dogs.

    Science.gov (United States)

    Zhang, Hang-Xiang; Zang, Yi-Min; Huo, Jian-Hua; Liang, Shao-Jun; Zhang, Hai-Feng; Wang, Yue-Min; Fan, Qian; Guo, Wen-Yi; Wang, Hai-Chang; Gao, Feng

    2006-12-01

    This study was designed to examine whether physiologically tolerable insulin, which maintains lower blood glucose, can protect the myocardium against ischemia/reperfusion (I/R) injury in a preclinical large animal model. Adult dogs were subjected to 50 minutes of myocardial ischemia (80% reduction in coronary blood flow) followed by 4 hours of reperfusion and treated with vehicle, glucose-insulin-potassium (GIK; glucose, 250 g/L; insulin, 60 U/L; potassium, 80 mmol/L), GK, or low-dose insulin (30 U/L) 10 minutes before reperfusion. Treatment with GIK exerted significant cardioprotective effects as evidenced by improved cardiac function, improved coronary blood flow, reduced infarct size, and myocardial apoptosis. In contrast, treatment with GK increased blood glucose level and aggravated myocardial I/R injury. It is interesting that treatment with insulin alone at the dose that reduced blood glucose to a clinically tolerable level exerted significant cardioprotective effects that were comparable to that seen in the GIK-treated group. This low-dose insulin had no effect on coronary blood flow after reperfusion but markedly reduced coronary reactive hyperemia and switched myocardial substrate uptake from fat to carbohydrate. Our results suggest that lower glucose supply to the ischemic myocardium at early reperfusion may create a "metabolic postconditioning" and thus reduce myocardial ischemia/reperfusion injury after prolonged reperfusion.

  8. Magnetic Resonance Imaging (MRI) Analysis of Ischemia/Reperfusion in Experimental Acute Renal Injury.

    Science.gov (United States)

    Pohlmann, Andreas; Arakelyan, Karen; Seeliger, Erdmann; Niendorf, Thoralf

    2016-01-01

    Imbalance between renal oxygen delivery and demand in the first hours after reperfusion is suggested to be decisive in the pathophysiological chain of events leading to ischemia-induced acute kidney injury. Here we describe blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) for continuous monitoring of the deoxyhemoglobin-sensitive MR parameter T 2* in the renal cortex, outer medulla, and inner medulla of rats throughout renal ischemia/reperfusion (I/R). Changes during I/R are benchmarked against the effects of variations in the fraction of inspired oxygen (hypoxia, hyperoxia). This method may be useful for investigating renal blood oxygenation of rats in vivo under various experimental (patho)physiological conditions.

  9. Pharmacological preconditioning with hyperbaric oxygen: can this therapy attenuate myocardial ischemic reperfusion injury and induce myocardial protection via nitric oxide?

    Science.gov (United States)

    Yogaratnam, Jeysen Zivan; Laden, Gerard; Guvendik, Lavent; Cowen, Mike; Cale, Alex; Griffin, Steve

    2008-09-01

    Ischemic reperfusion injury (IRI) is an inevitable part cardiac surgery such as coronary artery bypass graft (CABG). While ischemic hypoxia and the ensuing normoxic or hyperoxic reperfusion are critical to the initiation and propagation of IRI, conditioning myocardial cells to an oxidative stress prior to IRI may limit the consequences of this injury. Hyperbaric oxygen (HBO2) is a modality of treatment that is known to generate an oxidative stress. Studies have shown that treatment with HBO2 postischemia and reperfusion is useful in ameliorating myocardial IRI. Moreover, preconditioning the myocardium with HBO2 before reperfusion has demonstrated a myocardial protective effect by limiting the infarct size post ischemia and reperfusion. Current evidence suggests that HBO2 preconditioning may partly attenuate IRI by stimulating the endogenous production of nitric oxide (NO). As NO has the capacity to reduce neutrophil sequestration, adhesion and associated injury, and improve vascular flow, HBO2 preconditioning induced NO may play a role in providing myocardial protection during interventions that involve an inevitable episode of IRI. This current opinion review article attempts to suggest that HBO2 may be used to pharmacologically precondition and protect the myocardium from the effects of IRI that is known to occur during cardiac surgery.

  10. Systemic gene therapy with interleukin-13 attenuates renal ischemia-reperfusion injury

    NARCIS (Netherlands)

    Sandovici, M.; Henning, R. H.; van Goor, H.; Helfrich, W.; de Zeeuw, D.; Deelman, L. E.

    2008-01-01

    Ischemia-reperfusion injury is a leading cause of acute renal failure and a major determinant in the outcome of kidney transplantation. Here we explored systemic gene therapy with a modified adenovirus expressing Interleukin (IL)-13, a cytokine with strong anti-inflammatory and cytoprotective proper

  11. MRI of renal oxygenation and function after normothermic ischemia-reperfusion injury

    NARCIS (Netherlands)

    Oostendorp, M. van; Vries, E.E. de; Slenter, J.M.; Peutz-Kootstra, C.J.; Snoeijs, M.G.; Post, M.J.; Heurn, L.W. van; Backes, W.H.

    2011-01-01

    The in vivo assessment of renal damage after ischemia-reperfusion injury, such as in sepsis, hypovolemic shock or after transplantation, is a major challenge. This injury often results in temporary or permanent nonfunction. In order to improve the clinical outcome of the kidneys, novel therapies are

  12. Determinants of tubular bone marrow-derived cell engraftment after renal ischemia/reperfusion in rats

    NARCIS (Netherlands)

    Broekema, M; Harmsen, MC; Koerts, JA; Petersen, AH; van Luyn, MJA; Navis, G; Popa, ER

    2005-01-01

    Background. Ischemia/reperfusion (I/R) injury is a major cause of acute renal failure (ARF). ARF is reversible, due to an innate regenerative process, which is thought to depend partly on bone marrow-derived progenitor cells. The significance of these cells in the repair process has been questioned

  13. MRI of renal oxygenation and function after normothermic ischemia-reperfusion injury

    NARCIS (Netherlands)

    Oostendorp, M. van; Vries, E.E. de; Slenter, J.M.; Peutz-Kootstra, C.J.; Snoeijs, M.G.; Post, M.J.; Heurn, L.W. van; Backes, W.H.

    2011-01-01

    The in vivo assessment of renal damage after ischemia-reperfusion injury, such as in sepsis, hypovolemic shock or after transplantation, is a major challenge. This injury often results in temporary or permanent nonfunction. In order to improve the clinical outcome of the kidneys, novel therapies are

  14. MCT1 and MCT4 Expression During Myocardial Ischemic-Reperfusion Injury in the Isolated Rat Heart

    Directory of Open Access Journals (Sweden)

    Yi Zhu

    2013-09-01

    Full Text Available Background/Aims: Myocardium ischemia-reperfusion (I/R injury can be caused by imbalances in cellular metabolism. Lactate, transported by monocarboxylate transporters (MCTs, has been implicated as a mechanism in this process. The present study was designed to investigate the expression and functional role of MCTs in rat hearts during ischemia and reperfusion. Methods: Langendorff-perfused rat hearts were subjected to 20 minutes stabilization, 30 minutes of global ischemia and 60 minutes reperfusion. Hearts were collected serially for detecting expression changes in MCT1, MCT4 during myocardial I/R injury and lactate concentration was measured. Post-ischemic left ventricular function and infract size were determined at end-point, followed by the pretreatment of D-lactate, a competitive inhibitor of MCTs. Results: MCT4 was significantly increased following global ischemia and MCT1 expression was increased during the early stages of reperfusion in isolated rat hearts, while the expression of the ancillary protein CD147 was increased during I/R injury. We determined increases in AMPK phosphorylation status, which was significantly elevated following ischemia and early reperfusion. Blocking monocarboxylate transport by competitive inhibition with D-lactate caused decreased left ventricular performance and increased infarct size. Conclusion: Increased MCT4 expression facilitates lactate extrusion during the ischemic period, while increased MCT1 may facilitate lactate transport into and out of cells simultaneously during early reperfusion, with increases in AMPK phosphorylation status during the myocardial I/R period. Lactate transport by MCTs has a profound protective effect during myocardial ischemia reperfusion injury.

  15. Intermittent Ischemia but Not Ischemic Preconditioning Is Effective in Restoring Bile Flow After Ischemia Reperfusion Injury in the Livers of Aged Rats

    NARCIS (Netherlands)

    Schiesser, Marc; Wittert, Anna; Nieuwenhuijs, Vincent B.; Morphett, Arthur; Padbury, Robert T. A.; Barritt, Greg J.

    2009-01-01

    BackgroundlAims. Ischemic preconditioning (IPC) and intermittent ischemia (INT) reduce liver injury following ischemia reperfusion in liver resections. Aged livers are at higher risk for ischemia reperfusion injury, but little is known of the effectiveness of IPC and INT in aged livers. The aim of t

  16. Dynamic Contrast-Enhanced MR Imaging of Renal Ischemia-Reperfusion Injury

    Energy Technology Data Exchange (ETDEWEB)

    Baik, Jun Hyun; Ahn, Myeong Im; Park, Young Ha; Chung, Soo Kyo [Catholic University, Seoul (Korea, Republic of)

    2010-02-15

    To evaluate the usefulness of magnetic resonance imaging (MRI) in a renal ischemia-reperfusion injury. Twenty-four rabbits were randomly divided into four groups, including a sham operated group (n=3). Renal ischemia was induced for 30 minutes (group 1), 60 minutes (group 2) and 120 minutes (group 3). MR imaging was performed before ischemia as well as one hour, 24 hours, and 72 hours after reperfusion. A 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy was performed before ischemia, as well as 24 hours and 72 hours after reperfusion. The signal-to-noise ratio (SNR) on the T2WI, time-relative signal intensity (%RSI) curve on dynamic enhanced images, and relative left renal uptake (%) on DMSA scan were obtained and compared to the histologic findings. The SNR of the cortex on the T2WI changed significantly over the course of the reperfusion time (p<0.001), but was not significantly different among the ischemia groups. The area under the time-%RSI curve gradually decreased from cortex to inner medulla before ischemia, which was reversed and gradually increased after reperfusion. The areas under the time-%RSI curve of outer and inner medulla were significantly different among the ischemia groups (p=0.04, p=0.008). The relative renal uptake (%) of left kidney decreased significantly over the reperfusion time (p=0.03), and was also significantly different among the ischemia groups (p=0.005). Tubular cell necrosis was observed in 16 rabbits (76.2%). The histologic grades of group 3 were higher than those of group 1 and group 2 (p=0.002). Even in rabbits without tubular cell necrosis, the areas under the time-%RSI curves of the cortex, outer, and inner medulla after a 72 hour reperfusion time were significantly lower than those before ischemia (p=0.007, p=0.005, p=0.004). The results of this study suggest that dynamic enhanced MR imaging could be a useful tool for the evaluation of renal ischemia and reperfusion injury.

  17. Acute ischemic injury to the renal microvasculature in human kidney transplantation.

    NARCIS (Netherlands)

    Snoeijs, M.G.; Vink, H.; Voesten, N.; Christiaans, M.H.; Daemen, J.W.; Peppelenbosch, A.G.; Tordoir, J.H.; Peutz-Kootstra, C.J.; Buurman, W.A.; Schurink, G.W.; Heurn, L.W.E. van

    2010-01-01

    Increased understanding of the pathophysiology of ischemic acute kidney injury in renal transplantation may lead to novel therapies that improve early graft function. Therefore, we studied the renal microcirculation in ischemically injured kidneys from donors after cardiac death (DCD) and in living

  18. Effect of sildenafil in renal ischemia/reperfusion injury in rats Efeito do sildenafil na lesão renal por isquemia/reperfusão em ratos

    Directory of Open Access Journals (Sweden)

    Paulo José de Medeiros

    2010-12-01

    Full Text Available PURPOSE: To evaluate the effect of sildenafil, administered prior to renal ischemia/reperfusion (I/R, by scintigraphy and histopathological evaluation in rats. METHODS: Twenty-four rats were divided randomly into two groups. They received 0.1 ml of 99mTechnetium-etilenodicisteine intravenous, and a baseline (initial renal scintigraphy was performed. The rats underwent 60 minutes of ischemia by left renal artery clamping. The right kidney was not manipulated. The sildenafil group (n=12 received orally 1 mg/kg of sildenafil suspension 60 minutes before ischemia. Treatment with saline 0.9% in the control group (n=12. Half of the rats was assessed after 24 hours and half after seven days I/R, with new renal scintigraphy to study differential function. After euthanasia, kidneys were removed and subjected to histopathological examination. For statistical evaluation, Student t and Mann-Whitney tests were used. RESULTS: In the control group rats, the left kidneys had significant functional deficit, seven days after I/R, whose scintigraphic pattern was consistent with acute tubular necrosis, compared with the initial scintigraphy (pOBJETIVO: Estudar o efeito do sildenafil, administrado previamente à isquemia/reperfusão (I/R renal, em avaliações cintilográficas e histopatológicas em ratos. MÉTODOS: Vinte e quatro ratos Wistar foram aleatoriamente distribuídos em dois grupos. Os animais receberam 0,1 ml IV de 99mTecnécio-Etilenodicisteína, foram submetidos à cintilografia renal inicial e em seguida submetidos a isquemia no rim esquerdo, com oclusão da artéria renal, durante 60 minutos, com posterior reperfusão. O grupo sildenafil (n=12 recebeu previamente 1mg/kg de sildenafil em suspensão 60 minutos antes da isquemia. Solução salina 0,9% foi administrada no grupo controle (n=12. Metade dos animais de cada grupo foi avaliada após 24 horas e a outra metade após sete dias de reperfusão, com nova cintilografia renal. Após eutanásia, os

  19. 丙酮酸乙酯对肾缺血/再灌注损伤小鼠炎症因子及丝裂素活化蛋白激酶表达的影响%Effect of ethyl pyruvate on expression of inflammatory factors and mitogen-activated protein kinase proteins in renal ischemic/reperfusion injury in BABL/c mice

    Institute of Scientific and Technical Information of China (English)

    徐欣晖; 陈琦; 陈怡; 吕利雄; 朱长清; 戴慧丽; 钱家麒

    2010-01-01

    Objective To investigate the effects of ethyl pyruvate(EP) on expression of proinflammatory related gene and proteins of mitogen-activated protein kinase(MAPK) in renal tissues in ischemic/reperfusion(I/R) injury in mice. Methods Fifty male BABL/c mice were randomly divided into sham operation group(n=8),model group(n=10),and EP treatment group(n=32).EP treatment group was subdivided into EP pretreatment group(administration of 40 mg/kg EP 30 minutes before reproduction of model,n=8),and 4,6 and 12 hours treatment groups(administration of 40 mg/kg EP 4,6 and 12 hours after reproduction of model,respectively,n=8 in each group).Bilateral renal artery was occluded with a microvascular clamp for 30 minutes to reproduce kidney I/R injury model,and the kidney was harvested at 24 hours after I/R.The mRNA expressions of interleukins(IL-1β,IL-6),tumor necrosis factor-α(TNF-α),intercellular adhesion molecule-1(ICAM-1) and high-mobility group box 1(HMGB1) were determined by real time reverse transcription-polymerase chain reaction(RT-PCR).The changes in protein levels of MAPKs[extracellular regulated protein kinase 1/2(ERK1/2),c-Jun N-terminal kinase(JNK),p38MAPK] were determined by Western blotting analysis. Results Real-time PCR assay showed that the mRNA expressions of IL-1β,IL-6,TNF-α,ICAM-1,HMGB1 in renal tissue were much higher than those in sham operation group(IL-1β:12.05±8.08 vs.3.18±1.13,IL-6:10.26±6.85 vs.0.81±0.34,TNF-α:5.83±3.85 vs.0.67±0.34,ICAM-1:3.87±2.02 vs.0.29±0.13,HMGB1:652.82±78.50 vs.112.31±32.50,all P<0.05);and the expression in EP treatment groups was markedly down-regulated than that in model group,especially in 12-hour treatment group(0.45±0.26,0.66±0.13,0.21±0.11,0.05±0.02,212.26±3.20,respectively,all P<0.05).Western blotting analysis revealed that the expression of the phosphorylated forms of ERK1/2,JNK,p38MAPK proteins was significantly higher than in sham operation group(p-ERK1/2:1.13±0.38 vs.0.48±0.34,p-JNK:1.40±0.15 vs

  20. The anti-coagulants asis or apc do not protect against renal ischemia/ reperfusion injury

    Directory of Open Access Journals (Sweden)

    Sarah T.B.G. Loubele

    2014-06-01

    Full Text Available Renal ischemia/reperfusion (I/R injury is the main cause of acute renal failure. The severity of injury is determined by endothelial damage as well as inflammatory and apoptotic processes. The anticoagulants active site inhibited factor VIIa (ASIS and activated protein C (APC are besides their anticoagulant function also known for their cytoprotective properties. In this study the effect of ASIS and APC was assessed on renal I/R injury and this in relation to inflammation and apoptosis. Our results showed no effect of ASIS or APC on renal injury as determined by histopathological scoring as well as by blood urea nitrogen (BUN and creatinine levels. Furthermore, no effect on fibrin staining was detected but ASIS did reduce tissue factor activity levels after a 2-hr reperfusion period. Neither ASIS nor APC administration influenced overall inflammation markers, although some inflammatory effects of ASIS on interleukin (IL-1β and tumor necrosis factor (TNF-α were detectable after 2 hr of reperfusion. Finally, neither APC nor ASIS had an influence on cell signaling pathways or on the number of apoptotic cells within the kidneys. From this study we can conclude that the anticoagulants ASIS and APC do not have protective effects in renal I/R injury in the experimental setup as used in this study which is in contrast to the protective effects of these anticoagulants in other models of I/R.

  1. Protective effects of captopril in diabetic rats exposed to ischemia/reperfusion renal injury.

    Science.gov (United States)

    Fouad, Amr A; Al-Mulhim, Abdulruhman S; Jresat, Iyad; Morsy, Mohamed A

    2013-02-01

    To investigate the potential protective effects of captopril, the angiotensin-converting enzyme inhibitor, in diabetic rats exposed to ischaemia/reperfusion (I/R) renal injury. Following successful induction of diabetes, captopril treatment (50 mg/kg/day, p.o.) was applied for 4 weeks, after which bilateral renal ischaemia was induced for 30 min followed by reperfusion for 24 h. Captopril significantly attenuated hyperglycaemia and hypoinsulinaemia in diabetic rats, and significantly reduced the elevations of serum creatinine and aldosterone levels, and renal malondialdehyde, tumour necrosis factor-α and nitric oxide (NO), and prevented the depletion of reduced glutathione caused by I/R in diabetic rats. Histopathological renal tissue damage induced by I/R in diabetic rats was ameliorated by captopril treatment. Immunohistochemical analysis revealed that captopril significantly attenuated the reduction of insulin content in pancreatic islet β-cells, and decreased the I/R-induced expression of inducible NO synthase, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin and heme oxygenase-1 in the kidney tissue of diabetic rats. Captopril represents a potential candidate to reduce the risk of renal injury induced by ischaemia/reperfusion in type 2 diabetes. © 2012 The Authors. JPP © 2012. Royal Pharmaceutical Society.

  2. Thrombin inhibition with melagatran does not attenuate renal ischaemia-reperfusion injury in rats

    DEFF Research Database (Denmark)

    Nitescu, Nicoletta; Grimberg, Elisabeth; Ricksten, Sven-Erik;

    2007-01-01

    to renal IR. METHODS: Sprague-Dawley rats underwent renal IR (35 min of bilateral renal arterial clamping), or sham surgery. Treatment groups were: (i) IR-Saline, (ii) IR-Melagatran, (iii) Sham-Saline, and (iv) Sham-Melagatran. Twenty minutes prior to renal IR, the rats were administered a bolus dose......BACKGROUND: Renal ischaemia-reperfusion (IR) is associated with activation of the coagulation system and inflammation within the kidney. The aim of the present study was to examine the effects of selective thrombin inhibition with melagatran on kidney morphology and function in rats subjected...... of saline vehicle or melagatran [0.5 mumol/kg, subcutaneously (s.c.)] followed by a continuous infusion throughout (0.08 micromol/kg/h, s.c.). Forty-eight hours after IR, renal function was assessed in anaesthetized animals and kidney histology was analysed semi-quantitatively. RESULTS: Rats in group IR...

  3. Gene control of acupuncture and moxibustion preconditioning on apoptosis in ischemic cardiac muscle of rats with re-perfusion

    Institute of Scientific and Technical Information of China (English)

    SUN Zhong-ren; LI Xiao-ning; ZHAO Yu-hui; TIAN Yan-yan; XU Li

    2008-01-01

    In order to explore the effect of acupuncture preconditioning on rats' cell apoptosis with cardiac muscle re-perfusion damage and bcl-2mRNA genes, we used differentiating acupuncture and moxibustion preconditioning among groups, then compared acupuncture and moxibustion preconditioning with ischemic preconditioning. The experimental results show that acupuncture and moxibustion preconditioning makes more bcl-2mRNA genes expressed and produces less cell apeptosis, furthermore, groups of acupuncture and moxibustion preconditioning for twice a day are more effective than those of ischemic preconditioning.

  4. Modulation of The Balance Between Cannabinoid CB1 and CB2 Receptor Activation During Cerebral Ischemic/Reperfusion Injury

    OpenAIRE

    ZHANG, Ming; Martin, Billy R.; Adler, Martin W.; Razdan, Raj K.; Ganea, Doina; Tuma, Ronald F.

    2008-01-01

    Cannabinoid receptor activation has been shown to modulate both neurotransmission (CB1) and neuroinflammatory (CB2) responses. There are conflicting reports in the literature describing the influence of cannabinoid receptor activation on ischemic/reperfusion injury. The goal of this study was to evaluate how changing the balance between CB1 and CB2 activation following cerebral ischemia influences outcome. CB1 and CB2 expression were tested at different times after transient middle cerebral a...

  5. Renal ischemia/reperfusion-induced cardiac hypertrophy in mice: Cardiac morphological and morphometric characterization

    Science.gov (United States)

    Cirino-Silva, Rogério; Kmit, Fernanda V; Trentin-Sonoda, Mayra; Nakama, Karina K; Panico, Karine; Alvim, Juliana M; Dreyer, Thiago R; Martinho-Silva, Herculano

    2017-01-01

    Background Tissue remodeling is usually dependent on the deposition of extracellular matrix that may result in tissue stiffness and impaired myocardium contraction. Objectives We had previously demonstrated that renal ischemia/reperfusion (I/R) is able to induce development of cardiac hypertrophy in mice. Therefore, we aimed to characterize renal I/R-induced cardiac hypertrophy. Design C57BL/6 J mice were subjected to 60 minutes’ unilateral renal pedicle occlusion, followed by reperfusion (I/R) for 5, 8, 12 or 15 days. Gene expression, protein abundance and morphometric analyses were performed in all time points. Results Left ventricle wall thickening was increased after eight days of reperfusion (p < 0.05). An increase in the number of heart ventricle capillaries and diameter after 12 days of reperfusion (p < 0.05) was observed; an increase in the density of capillaries starting at 5 days of reperfusion (p < 0.05) was also observed. Analyses of MMP2 protein levels showed an increase at 15 days compared to sham (p < 0.05). Moreover, TGF-β gene expression was downregulated at 12 days as well TIMP 1 and 2 (p < 0.05). The Fourier-transform infrared spectroscopy analysis showed that collagen content was altered only in the internal section of the heart (p < 0.05); such data were supported by collagen mRNA levels. Conclusions Renal I/R leads to impactful changes in heart morphology, accompanied by an increase in microvasculature. Although it is clear that I/R is able to induce cardiac remodeling, such morphological changes is present in only a section of the heart tissue.

  6. Lazaroid U-74389G Administration in Pancreatic Ischemia-Reperfusion Injury: A Swine Model Encompassing Ischemic Preconditioning.

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    Chrysikos, Dimosthenis T; Sergentanis, Theodoros N; Zagouri, Flora; Psaltopoulou, Theodora; Theodoropoulos, George; Flessas, Ioannis; Agrogiannis, George; Alexakis, Nikolaos; Lymperi, Maria; Katsarou, Ageliki I; Patsouris, Efstratios S; Zografos, Constantine G; Papalois, Apostolos E

    2015-03-20

    The potential of lazaroid U-74389G in attenuating injury after ischemia and reperfusion has been reported in various organs. The present study focuses specifically on the pancreas and aims to examine any effects of U-74389G in a swine model of pancreatic ischemia and reperfusion, encompassing ischemic preconditioning. Twelve pigs, weighing 28-35 kg, were randomized into two experimental groups. Group A (control group, n=6): Two periods of ischemic preconditioning (5 min each) separated by a 5-min rest interval; then ischemia time 30 min and reperfusion for 120 min. Group B (n=6): the same as above, with U-74389G intravenous injection in the inferior vena cava immediately prior to the initiation of reperfusion. Blood sampling and pancreatic biopsies were conducted at 0, 30, 60, 90 and 120 min after reperfusion. Repeated-measures ANOVA was undertaken to evaluate differences between the two study groups. No statistically significant differences were noted concerning the histopathological parameters in the control and therapy groups (P=0.563 for edema, P=0.241 for hemorrhage, P=0.256 for leukocyte infiltration, P=0.231 for acinar necrosis and P=0.438 for vacuolization). In accordance with the above, serum metabolic data (glucose, creatinine, urea, total and direct bilirubin, total calcium, amylase, lipase, SGOT/AST, SGPT/ALT, ALP, GGT, LDH, CRP, insulin) were not significantly different between the two groups; similarly, tumor necrosis factor-α values (P=0.705) and tissue malondialdehyde levels (P=0.628) did not differ between the two groups. This swine model of pancreatic ischemia and reperfusion, encompassing preconditioning, indicates that U-74389G lazaroid does not seem to exert protective effects from pancreatic damage.

  7. Lazaroid U-74389G Administration in Pancreatic Ischemia-Reperfusion Injury: A Swine Model Encompassing Ischemic Preconditioning

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    Dimosthenis T Chrysikos

    2015-05-01

    Full Text Available Context The potential of lazaroid U-74389G in attenuating injury after ischemia and reperfusion has been reported in various organs. Objective The present study focuses specifically on the pancreas and aims to examine any effects of U-74389G in a swine model of pancreatic ischemia and reperfusion, encompassing ischemic preconditioning. Methods Twelve pigs, weighing 28–35 kg, were randomized into two experimental groups. Group A (control group, n=6: Two periods of ischemic preconditioning (5 min each separated by a 5- min rest interval; then ischemia time 30 min and reperfusion for 120 min. Group B (n=6: the same as above, with U-74389G intravenous injection in the inferior vena cava immediately prior to the initiation of reperfusion. Blood sampling and pancreatic biopsies were conducted at 0, 30, 60, 90 and 120 min after reperfusion. Results Repeated-measures ANOVA was undertaken to evaluate differences between the two study groups. No statistically significant differences were noted concerning the histopathological parameters in the control and therapygroups (P=0.563 for edema, P=0.241 for hemorrhage, P=0.256 for leukocyte infiltration, P=0.231 for acinar necrosis and P=0.438 for vacuolization. In accordance with the above, serum metabolic data (glucose, creatinine, urea, total and direct bilirubin, total calcium, amylase, lipase, SGOT/AST, SGPT/ALT, ALP, GGT, LDH, CRP, insulin were not significantly different between the two groups; similarly, tumor necrosis factor-α values (P=0.705 and tissue malondialdehyde levels (P=0.628 did not differ between the two groups. Conclusion This swine model of pancreatic ischemia and reperfusion, encompassing preconditioning, indicates that U-74389G lazaroid does not seem to exert protective effects from pancreatic damage.

  8. Intravenous Administration of Cilostazol Nanoparticles Ameliorates Acute Ischemic Stroke in a Cerebral Ischemia/Reperfusion-Induced Injury Model

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    Noriaki Nagai

    2015-12-01

    Full Text Available It was reported that cilostazol (CLZ suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.2% docusate sodium salt, and mill methods (CLZnano dispersion; particle size 81 ± 59 nm, mean ± S.D., and investigated their toxicity and usefulness in a cerebral ischemia/reperfusion-induced injury model (MCAO/reperfusion mice. The pharmacokinetics of injections of CLZnano dispersions is similar to that of CLZ solutions prepared with 2-hydroxypropyl-β-cyclodextrin, and no changes in the rate of hemolysis of rabbit red blood cells, a model of cell injury, were observed with CLZnano dispersions. In addition, the intravenous injection of 0.6 mg/kg CLZnano dispersions does not affect the blood pressure and blood flow, and the 0.6 mg/kg CLZnano dispersions ameliorate neurological deficits and ischemic stroke in MCAO/reperfusion mice. It is possible that the CLZnano dispersions will provide effective therapy for ischemic stroke patients, and that injection preparations of lipophilic drugs containing drug nanoparticles expand their therapeutic usage.

  9. In vivo quantification of VCAM-1 expression in renal ischemia reperfusion injury using non-invasive magnetic resonance molecular imaging.

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    Asim M Akhtar

    Full Text Available RATIONALE AND OBJECTIVE: Vascular cell adhesion molecule-1 (VCAM-1 is upregulated in ischemia reperfusion injury (IRI, persisting after restoration of blood flow. We hypothesized that microparticles of iron oxide targeting VCAM-1 (VCAM-MPIO would depict "ischemic memory" and enable in vivo assessment of VCAM-1 expression. METHODOLOGY AND FINDINGS: Mice subject to unilateral, transient (30 minutes renal ischemia and subsequent reperfusion received intravenous VCAM-MPIO (4.5 mg iron/kg body weight. Contrast agent bound rapidly (<30 minutes in IRI-kidneys and appeared as intensely low signal areas by MRI in vivo. Automated segmentation and quantification yielded MPIO contrast volumes of 5991±354×10(6 µm(3 in IRI vs. 87±7×10(6 µm(3 in kidneys with no surgical intervention (P<0.001; 90±8×10(6 µm(3 in IRI kidneys exposed to control (IgG-MPIO and 625±80×10(6 µm(3, in IRI kidneys pre-treated with a blocking dose of VCAM-1 antibody (P<0.001. In keeping with quantitative MRI data, VCAM-1 mRNA expression in IRI was 65-fold higher than in kidneys without surgical intervention (3.06±0.63 vs. 0.05±0.02, P<0.001. Indeed VCAM-1 mRNA expression and VCAM-MPIO contrast volume were highly correlated (R(2=0.901, P<0.01, indicating that quantification of contrast volume reflected renal VCAM-1 transcription. Serial imaging showed VCAM-MPIO accumulation at target within 30 minutes, persisting for ≥90 minutes, while unbound VCAM-MPIO was cleared rapidly from blood, with sequestration by mac-3 positive Kupffer cells in the liver and monocyte/macrophages in the spleen. CONCLUSIONS: (1 VCAM-MPIO detected VCAM-1 expression and defined its 3-dimensional distribution, revealing "ischemic memory" in renal IRI; (2 automated volumetric quantification of VCAM-MPIO accurately reflected tissue levels of VCAM-1 mRNA; and (3 VCAM-MPIO bound rapidly to target with active sequestration of unbound MPIO in the liver and spleen.

  10. Accelerated recovery of renal mitochondrial and tubule homeostasis with SIRT1/PGC-1α activation following ischemia–reperfusion injury

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    Funk, Jason A., E-mail: funkj@musc.edu [Center for Cell Death, Injury, and Regeneration, Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Schnellmann, Rick G., E-mail: schnell@musc.edu [Center for Cell Death, Injury, and Regeneration, Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425 (United States); Ralph H. Johnson VA Medical Center, Charleston, SC 29401 (United States)

    2013-12-01

    Kidney ischemia–reperfusion (I/R) injury elicits cellular injury in the proximal tubule, and mitochondrial dysfunction is a pathological consequence of I/R. Promoting mitochondrial biogenesis (MB) as a repair mechanism after injury may offer a unique strategy to restore both mitochondrial and organ function. Rats subjected to bilateral renal pedicle ligation for 22 min were treated once daily with the SIRT1 activator SRT1720 (5 mg/kg) starting 24 h after reperfusion until 72 h–144 h. SIRT1 expression was elevated in the renal cortex of rats after I/R + vehicle treatment (IRV), but was associated with less nuclear localization. SIRT1 expression was even further augmented and nuclear localization was restored in the kidneys of rats after I/R + SRT1720 treatment (IRS). PGC-1α was elevated at 72 h–144 h in IRV and IRS kidneys; however, SRT1720 treatment induced deacetylation of PGC-1α, a marker of activation. Mitochondrial proteins ATP synthase β, COX I, and NDUFB8, as well as mitochondrial respiration, were diminished 24 h–144 h in IRV rats, but were partially or fully restored in IRS rats. Urinary kidney injury molecule-1 (KIM-1) was persistently elevated in both IRV and IRS rats; however, KIM-1 tissue expression was attenuated in IRS rats. Additionally, sustained loss of Na{sup +},K{sup +}–ATPase expression and basolateral localization and elevated vimentin in IRV rats was normalized in IRS rats, suggesting restoration of a differentiated, polarized tubule epithelium. The results suggest that SRT1720 treatment expedited recovery of mitochondrial protein expression and function by enhancing MB, which was associated with faster proximal tubule repair. Targeting MB may offer unique therapeutic strategy following ischemic injury. - Highlights: • We examined recovery of mitochondrial and renal function after ischemia–reperfusion. • SRT1720 treatment after I/R induced mitochondrial biogenesis via SIRT1/PGC-1α. • Recovery of mitochondrial function was

  11. Reperfusion therapy for ischemic stroke in the Russian Federation: Problems and promises

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    N.A. Shamalov

    2014-01-01

    Full Text Available Current technologies for treating ischemic stroke (IS within the first 4.5 hours after its onset involve highly effective brain substance reperfusion techniques (thrombolytic therapy (TLT aimed at restoring blood flow in the affected vessel. There has been a substantial increase in the number of systemic TLT procedures after establishing stroke subdivisions as part of regional vascular centers and primary vascular departments in our country. In the past 5 years, the number of IS patients undergoing systemic thrombolysis has virtually risen 10-fold. In 2009–2013, the primary and regional centers of the Russian Federation performed 10,718 systemic TLT procedures mainly in patients with moderate stroke. The further increase in the number of reperfusion procedures in IS patients is hindered by the fact that they seek medical advice too late for acute cerebrovascular attack (ACVA because the population has low medical knowledge (therefore education campaigns are so important for the population to increase its awareness of the signs of ACVA, prehospital delays and problems, poor organization of hospital admission (delays in diagnostic procedures.It is important that the patients should be admitted to specialized ACVA departments as soon as possible. According to the AHA/ASA guidelines, the time between admission and TLT initiation (door-to-needle time should not exceed 60 minutes. The major factors influencing the door-to-needle time are as follows: the time between admission and neurological examination, that between neuroimaging and its results, that of examination of necessary laboratory findings, that between admission and transfer to an intensive care unit after computed tomography. One may identify the following quality indices of the procedures (necessary diagnostic, therapeutic, and other interventions, which negatively affect the safety and efficiency of TLT: errors in determining contraindications to reperfusion, noncompliance with the

  12. The effect of erythropoietin on serum uric acid levels during renal ischemia reperfusion injury in rats

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    Tsompos, Constantinos; Panoulis, Constantinos; Toutouzas, Konstantinos; Zografos, George; Papalois, Apostolos

    2014-01-01

    Objective: The aim of this experimental study was to assess the effect of erythropoietin on a rat model, particularly under a renal ischemia reperfusion protocol. The beneficial or lack of effects of that molecule on the excreted renal product of serum uric acid were studied biochemically. Material and methods: Forty rats were used with a mean weight of 247.7 gr. Serum uric acid levels were measured measured at 60 min after reperfusion (Groups A and C) and at 120 min after reperfusion (groups B and D). Results: 1) Erythropoietin administration non-significantly decreased the serum uric acid levels non-significantly by 0.02 mg/dL [−0.2415423 mg/dL-0.2015423 mg/dL] (p=0.8560), in accordance with the paired t-test (p=0.8438). Reperfusion time non-significantly increased the serum uric acid levels non-significantly by 0.17 mg/dL [−0.0444933 mg/dL-0.3844933 mg/dL] (p=0.1169), in accordance with the paired t-test (p=0.1648). 3) The interaction of erythropoietin administration and reperfusion time non-significantly increased the serum uric acid levels non-significantly by 0.1 mg/dL [−0.0295564 mg/dL-0.2295564 mg/dL] (p=0.1264). Conclusion: Erythropoietin administration, reperfusion time and their interaction have no significant short-term alterations on serum uric acid levels. Conclusions cannot be extracted by non-significant p-values within 2 hours. Obviously, longer study times may permit safer results. PMID:26328161

  13. Combination Anti-Apoptotic Effect of Erythropoietin and Melatonin on Ischemia Reperfusion-Induced Renal Injury in Rats

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    Shokofeh Banaei

    2016-11-01

    Full Text Available Renal ischemia-reperfusion (IR contributes to the development of acute renal failure (ARF. Oxygen free radicals are considered to be principal components involved in the pathophysiological tissue alterations observed during renal IR. The purpose of this study was to investigate the combination effect of melatonin (MEL and erythropoietin (EPO, which are a potent antioxidant and anti-apoptotic agents, in IR-induced renal injury in rats. Wistar Albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h reperfusion. MEL (10 mg/kg, i.p and EPO (5000 U/kg, i.p were administered prior to ischemia. After 24 h reperfusion, following decapitation, blood samples were collected for the determination of superoxide dismutase (SOD, glutathione peroxidase (GPx, and malondialdehyde (MDA levels. Also, renal samples were taken for histological evaluation and apoptosis assay. Ischemia-reperfusion increased SOD, GPx, MDA levels, and TUNEL positive cells. Histopathological findings of the IR group confirmed that there was renal impairment in the tubular epithelium. Treatment with EPO and MEL decreased SOD, GPx, and MDA levels, histopathological changes, and TUNEL positive cells. These results indicated that the combination of MEL and EPO could not exert more nephroprotective and anti-apoptotic effects than MEL treatment in renal ischemia-reperfusion injury.

  14. Inflammation and innate immunity in renal ischemia/reperfusion injury

    NARCIS (Netherlands)

    Vries, Dorottya Katalin de

    2013-01-01

    The studies in this thesis describe the systematical search for factors involved in the pathophysiology of human renal I/R injury. Many of the processes assumed to be involved in renal I/R injury based on animal studies could not be confirmed in our clinical study in humans. However, we found new ev

  15. Detection and evaluation of renal biomarkers in a swine model of acute myocardial infarction and reperfusion.

    Science.gov (United States)

    Duan, Su-Yan; Xing, Chang-Ying; Zhang, Bo; Chen, Yan

    2015-01-01

    The prevalence of type 1 cardiorenal syndrome (CRS) is increasing and strongly associated with long-term mortality. However, lack of reliable animal models and well-defined measures of renoprotection, made early diagnosis and therapy difficult. We previously successfully established the swine acute myocardial infarction (AMI) model of ischemia-reperfusion by blocking left anterior descending branch (LAD). Reperfusion was performed after 90-minute occlusion of the LAD. AMI was confirmed by ECG and left ventricular angiography (LVG). Then those 52 survived AMI reperfusion swine, including ventricular fibrillation-cardiac arrest after restoration of blood flow, were randomly divided into four groups (four/group) according to different interventions: resuscitation in room temperature, resuscitation with 500 ml saline in room temperature, resuscitation with 4°C 500 ml saline and normal control (with no intervention of resuscitation). Each group was further observed in four groups according to different time of resuscitation after ventricular arrhythmias: 1, 3, 5, 10-minute reperfusion after ventricular arrhythmias. Plasma and random urine were collected to evaluate renal function and test renal biomarkers of acute kidney injury (AKI). Our swine AMI model of ischemia-reperfusion provoked subclinical AKI with the elevation of the tubular damage biomarker, NGAL, IL-18 and L-FABP. Renal damage rapidly observed after hemodynamic instability, rather than observation after several hours as previously reported. The increasing rate of biological markers declined after interventions, however, its impact on the long-term prognosis remains to be further studied. These data show that elevation of tubular damage biomarkers without glomerular function loss may indicate appropriate timing for effective renoprotections like hypothermia resuscitation in type 1 CRS.

  16. Activation of SHH signaling pathway promotes vasculogenesis in post-myocardial ischemic-reperfusion injury.

    Science.gov (United States)

    Guo, Wei; Yi, Xin; Ren, Faxin; Liu, Liwen; Wu, Suning; Yang, Jun

    2015-01-01

    This study aimed to investigate the potential roles of sonic Hedgehog (SHH) expression in vasculogenesis in post-myocardial ischemic-reperfusion injury (MIRI) and its underlying mechanism. Cardiac microvascular endothelial cells (CMECs) isolated from the SD rat hearts tissues were used to construct the MIRI model. mRNA level of SHH in control cells and MIRI cells was detected using RT-PCR analysis. Furthermore, effects of SHH expression on CMECs viability and apoptosis were analyzed using MTT assay and Annexin-V-FITC kit respectively. Moreover, effects of SHH expression on the pathway signal proteins expression was analyzed using ELISA and western blotting. mRNA level of SHH was significantly decreased compared to the controls (PSHH application compared with the controls (PSHH application, as well as the SHH signal proteins including Patch-1, Gli1, Gli2 and SMO (PSHH application on biological factors levels were reversed by the SHH inhibitor application. This study suggested that SHH over expression may play a pivotal contribute role in vasculogenesis through activating the SHH signals in post-MIRI.

  17. [Ischemic-reperfusion paraplegia in the dog and its light microscopy imaging].

    Science.gov (United States)

    Sulla, I; Marsala, J; Radonák, J

    2004-02-01

    Paraplegia, which develops after operation on aorta, represents a real catastrophe for the patient and for the surgeon. The aim of the present work was to investigate the light microscopy picture of this complication and consequently better understand related processes. Twenty one adult dogs, cross breeds of both sexes, weight 18-25 kg, were divided into four groups: 1. Controls (n = 3); 2.30-min ischemia induced by occlusion of thoracic aorta by a tourniquet, followed for 30 min survival (n = 6); 3.30-min ischemia and 72 h of survival (n = 6); 4) 30-min ischemia and 6 days of survival (n = 6). All these manipulations were made in sterile conditions under general anesthesia. As soon as the planned time of survival passed, the animals were flushed out, in deep pentobarbital anesthesia, with 3,000 ml of sodium chloride and fixed with 3,000 ml of 10% neutral formaldehyde. Sections, 30 microns thick, from L3-S1 medulla segments were processed in the laboratory of Neurobiological Institute by the method of Nauta for light microscopy examination. Neurohistological picture was characterized by a marked damage of the medulla neurons. The changes proved to be irreversible and resulted, in the course of six days of survival, to death of the cells, characterized by their disintegration. The results indicate that the only rational procedure in conditions of threatening ischemic-reperfusion injury of medulla is to prevent it.

  18. Bone marrow-derived cells can acquire renal stem cells properties and ameliorate ischemia-reperfusion induced acute renal injury

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    Jia Xiaohua

    2012-09-01

    Full Text Available Abstract Background Bone marrow (BM stem cells have been reported to contribute to tissue repair after kidney injury model. However, there is no direct evidence so far that BM cells can trans-differentiate into renal stem cells. Methods To investigate whether BM stem cells contribute to repopulate the renal stem cell pool, we transplanted BM cells from transgenic mice, expressing enhanced green fluorescent protein (EGFP into wild-type irradiated recipients. Following hematological reconstitution and ischemia-reperfusion (I/R, Sca-1 and c-Kit positive renal stem cells in kidney were evaluated by immunostaining and flow cytometry analysis. Moreover, granulocyte colony stimulating factor (G-CSF was administrated to further explore if G-CSF can mobilize BM cells and enhance trans-differentiation efficiency of BM cells into renal stem cells. Results BM-derived cells can contribute to the Sca-1+ or c-Kit+ renal progenitor cells population, although most renal stem cells came from indigenous cells. Furthermore, G-CSF administration nearly doubled the frequency of Sca-1+ BM-derived renal stem cells and increased capillary density of I/R injured kidneys. Conclusions These findings indicate that BM derived stem cells can give rise to cells that share properties of renal resident stem cell. Moreover, G-CSF mobilization can enhance this effect.

  19. Expression of Nestin, Vimentin, and NCAM by Renal Interstitial Cells after Ischemic Tubular Injury

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    David Vansthertem

    2010-01-01

    Full Text Available This work explores the distribution of various markers expressed by interstitial cells in rat kidneys after ischemic injury (35 minutes during regeneration of S3 tubules of outer stripe of outer medulla (OSOM. Groups of experimental animals (n=4 were sacrificed every two hours during the first 24 hours post-ischemia as well as 2, 3, 7, 14 days post-ischemia. The occurrence of lineage markers was analyzed on kidney sections by immunohistochemistry and morphometry during the process of tubular regeneration. In postischemic kidneys, interstitial cell proliferation, assessed by 5-bromo-2′-deoxyuridine (BrdU and Proliferating Cell Nuclear Antigen (PCNA labeling, was prominent in outer medulla and reach a maximum between 24 and 72 hours after reperfusion. This population was characterized by the coexpression of vimentin and nestin. The density of -Neural Cell Adhesion Molecule (NCAM positive interstitial cells increased transiently (18–72 hours in the vicinity of altered tubules. We have also localized a small population of α-Smooth Muscle Actin (SMA-positive cells confined to chronically altered areas and characterized by a small proliferative index. In conclusion, we observed in the postischemic kidney a marked proliferation of interstitial cells that underwent transient phenotypical modifications. These interstitial cells could be implicated in processes leading to renal fibrosis.

  20. Slit2 prevents neutrophil recruitment and renal ischemia-reperfusion injury.

    Science.gov (United States)

    Chaturvedi, Swasti; Yuen, Darren A; Bajwa, Amandeep; Huang, Yi-Wei; Sokollik, Christiane; Huang, Liping; Lam, Grace Y; Tole, Soumitra; Liu, Guang-Ying; Pan, Jerry; Chan, Lauren; Sokolskyy, Yaro; Puthia, Manoj; Godaly, Gabriela; John, Rohan; Wang, Changsen; Lee, Warren L; Brumell, John H; Okusa, Mark D; Robinson, Lisa A

    2013-07-01

    Neutrophils recruited to the postischemic kidney contribute to the pathogenesis of ischemia-reperfusion injury (IRI), which is the most common cause of renal failure among hospitalized patients. The Slit family of secreted proteins inhibits chemotaxis of leukocytes by preventing activation of Rho-family GTPases, suggesting that members of this family might modulate the recruitment of neutrophils and the resulting IRI. Here, in static and microfluidic shear assays, Slit2 inhibited multiple steps required for the infiltration of neutrophils into tissue. Specifically, Slit2 blocked the capture and firm adhesion of human neutrophils to inflamed vascular endothelial barriers as well as their subsequent transmigration. To examine whether these observations were relevant to renal IRI, we administered Slit2 to mice before bilateral clamping of the renal pedicles. Assessed at 18 hours after reperfusion, Slit2 significantly inhibited renal tubular necrosis, neutrophil and macrophage infiltration, and rise in plasma creatinine. In vitro, Slit2 did not impair the protective functions of neutrophils, including phagocytosis and superoxide production, and did not inhibit neutrophils from killing the extracellular pathogen Staphylococcus aureus. In vivo, administration of Slit2 did not attenuate neutrophil recruitment or bacterial clearance in mice with ascending Escherichia coli urinary tract infections and did not increase the bacterial load in the livers of mice infected with the intracellular pathogen Listeria monocytogenes. Collectively, these results suggest that Slit2 may hold promise as a strategy to combat renal IRI without compromising the protective innate immune response.

  1. Erdosteine in renal ischemia-reperfusion injury: an experimental study in pigs.

    Science.gov (United States)

    Lee, Jae-Yeon; Kim, Hyun-Soo; Park, Chang-Sik; Kim, Myung-Cheol

    2010-01-01

    The aim of the present study was to investigate the effect of erdosteine on renal reperfusion injury. Twelve male Landrace and Yorkshire mixed pigs were randomly divided into two groups: untreated control group (I/R), erdosteine treated group (I/R + erdosteine). Each group is composed of six pigs, and the pigs were unilaterally nephrectomized and their contralateral kidneys were subjected to 30 min of renal pedicle occlusion. The elevations of creatinine and blood urea nitrogen levels were lower in the treated group compared with the control group. The catalase activity and the glutathione peroxidase activity were higher in the erdosteine group. As a result, this study suggests that the erdosteine treatment has a role of attenuation of renal I/R injury recovery of renal function in pig.

  2. Administration of aqueous extract of Desmodium gangeticum (L) root protects rat heart against ischemic reperfusion injury induced oxidative stress.

    Science.gov (United States)

    Kurian, Gino A; Paddikkala, Jose

    2009-02-01

    Myocardial reperfusion is believed to be associated with free radical injury. The present study evaluates the effect of aqueous extract of D. gangeticum (DG) on lipid peroxides and antioxidants in ischemic reperfused (IR) Wistar albino male rats. Significant elevation in lipid peroxide products (thiobarbituric acid reactive substances) and decreased activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) were observed in the rat hearts during ischemia reperfusion phase. Pre treatment of rats with aqueous extract of DG orally for 30 days showed significantly improved preservation of antioxidant enzymes and subsequent reduction in lipid peroxidation. But 2,3,5 triphenyl tetrazolium chloride (TTC) stained rat heart did not show much significant antioxidant enzyme activities and lipid peroxidation. On the other hand, TTC unstained rat heart showed significant improvement in the antioxidant activities indicating cardio protective effect of aqueous extract of DG in myocardium affected by ischemia reperfusion insult. The administration of DG to normal rats did not have any significant effect on any of the parameter studied. These results indicate that DG improves the antioxidant capacity of heart and attenuate the degree of lipid peroxidation after IR.

  3. Protective effects of Saffron hydroalcoholic extract against renal tissue damages induced by ischemia-reperfusion in rats

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    Houshang Najafi

    2014-06-01

    Full Text Available Background: The aim of this study was to investigate the protective effects of saffron hydroalcoholic extract against tissue damages induced by renal ischemia/reperfusion. Methods: In this experimental study, 40 male rats were randomly divided into 5 groups; 1. sham group which underwent surgery with no vessel occlusion and passed equivalent reperfusion period, 2. Ischemia/reperfusion group which received solvent of extract and went through surgery, bilateral renal ischemia for 30 min and 24-h reperfusion period (I/R. The other three groups underwent ischemia/reperfusion receiving saffron extracts of 5, 10 or 20 mg/kg/ip, respectively. At the end of reperfusion period, the left kidney tissue was collected and stained with hematoxylin-eosin for histological studies. Statistical analysis was performed using one-way ANOVA and Mann-Whitney tests. Results: Following ischemia/reperfusion, the size of Bowman's space increased significantly (P<0.001. In addition, cell necrosis in the tubules of the cortex and outer medulla, vascular congestion and tubular casts in the outer and inner medulla increased. However, the number of RBCs in glomerular capillaries decreased. Administration of saffron extract could significantly improve all the injuries by all three doses. Nevertheless, the effect of 20 mg dose was smaller. Conclusion: Intraperitoneal administration of saffron hydroalcoholic extract has protective effects against tissue damages induced by 30 min ischemia and 24-h reperfusion in the rat’s kidney.

  4. The effects of cilostazol on tissue oxygenation upon an ischemic-reperfusion injury in the mouse cerebrum.

    Science.gov (United States)

    Morikawa, Takayuki; Hattori, Katsuji; Kajimura, Mayumi; Suematsu, Makoto

    2010-01-01

    Although cilostazol, an inhibitor of cyclic nucleotide phosphodiesterase 3 (PDE3), is known to exert a potent antiplatelet function by raising intracellular cAMP concentration, its effect on cerebral microcirculation upon an ischemic insult is not clearly understood. To examine effects of cilostazol on the global ischemic injury in the brain, we first measured the plasma leakage using modified Miles assay after mice had been subjected to 60 min of a bilateral common carotid artery (BCCA) occlusion followed by reperfusion for 4 h. Oral treatment with cilostazol (30 mg/kg) significantly increased plasma leakage. This result led us to examine if the treatment with cilostazol recruits more capillaries leading to an increase in surface area for exchange and oxygen transport to tissues. To do so, we simultaneously measured degrees of tissue hypoxia and vessel perfusion. Pimonidazol was injected intraperitoneally 1 h before sacrifice and capillary patency was assessed by fluorescein isothiocyanate-labeled Lycopersicon esculentum lectin bound to the endothelial surface. Treatment with cilostazol markedly increased the capillary patency which was accompanied by a reduction in the hypoxic area. Although the treatment with cilostazol caused an increase in the flux of plasma proteins across endothelial barrier that may imply an adverse role after a BCCA occlusion, this increase in protein leakage was attributable to the increased surface area for exchange which in turn brought about a reduction in tissue hypoxia. Taken together cilostazol appears to produce a protective effect against the ischemic-reperfusion injury.

  5. [Emoxipin in reperfusion of ischemic myocardium in dogs: effects on infarct size and plasma creatine kinase activity].

    Science.gov (United States)

    Konorev, E A; Polumiskov, V Iu; Avilova, O A; Golikova, A P

    1990-09-01

    The effects of synthetic antioxidant emoxypine on infarct size and plasma creatine kinase (CK) activity was studied on open-chest anesthetized dogs with 180-min myocardial ischemia followed by reperfusion. Emoxypine (10 and 40 mg/kg) was injected intravenously, beginning since 120th min of coronary artery occlusion. Emoxypine (10 mg/kg) resulted in infarct size limitation and reduction in plasma CK activity. An increase in dose of emoxypine to 40 mg/kg largely attenuated its protective effect on infarct size. CK activity during post-ischemic reperfusion was even higher in emoxypine (40 mg/kg) group compared with control. Augmented CK leakage from irreversibly injured myocardium to plasma under these experimental conditions may be owing to preservation of microvascular integrity and improving of drainage of infarcted tissue exerted by emoxypine.

  6. Perioperative release of pro-regenerative biochemical signals from human renal allografts subjected to ischemia-reperfusion injury.

    Science.gov (United States)

    Błogowski, Wojciech; Dolegowska, Barbara; Budkowska, Marta; Sałata, Daria; Domański, Leszek; Starzynska, Teresa

    2014-02-01

    Complement-derived molecules modulate the intensity of renal ischemia-reperfusion injury and may lead to the generation of biochemical signals [such as stromal-derived factor-1 (SDF-1) or sphingosine-1-phosphate (S1P)], which stimulate tissue/organ regeneration after injury. We tested the association between perioperative C5b-9/membrane attack complex (MAC) levels and intensified erythrocyte lysis, and asked whether significant changes in the levels of pro-regenerative substances occur during the early phase of renal allograft reperfusion. Seventy-five recipients were enrolled and divided into the early, slow, and delayed graft function (DGF) groups. Perioperative blood samples were collected from the renal vein during consecutive minutes of reperfusion. Extracellular hemoglobin (eHb), albumin (plasma S1P transporter), 8-iPF2α-III isoprostane, SDF-1 and S1P concentrations were measured. Throughout the reperfusion period, erythrocyte lysis intensified and was most pronounced in the DGF group. However, perioperative eHb levels did not correlate significantly with C5b-9/MAC values, but rather with the intensity of oxidative stress. No significant changes were observed in S1P, its plasma transporter (albumin) or SDF-1 levels, which were relatively low in all groups throughout the reperfusion period. Our study therefore demonstrates that no known biochemical signal for bone marrow-derived stem cell mobilization is released from human renal allografts to the periphery during the early phase of reperfusion.

  7. Regulation of Expression of Renal Organic Anion Transporters OAT1 and OAT3 in a Model of Ischemia/Reperfusion Injury

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    Christina Preising

    2015-08-01

    Full Text Available Background: Recently, we gained evidence that impairment of rOat1 and rOat3 expression induced by ischemic acute kidney injury (AKI is mediated by COX metabolites and this suppression might be critically involved in renal damage. Methods: (i Basolateral organic anion uptake into proximal tubular cells after model ischemia and reperfusion (I/R was investigated by fluorescein uptake. The putative promoter sequences from hOAT1 (SLC22A6 and hOAT3 (SCL22A8 were cloned into a reporter plasmid, transfected into HEK cells and (ii transcriptional activity was determined after model ischemia and reperfusion as a SEAP reporter gen assay. Inhibitors or antagonists were applied with the beginning of reperfusion. Results: By using inhibitors of PKA (H89 and PLC (U73122, antagonists of E prostanoid receptor type 2 (AH6809 and type 4 (L161,982, we gained evidence that I/R induced down regulation of organic anion transport is mediated by COX1 metabolites via E prostanoid receptor type 4. The latter signaling was confirmed by application of butaprost (EP2 agonist or TCS2510 (EP4 agonist to control cells. In brief, the latter signaling was verified for the transcriptional activity in the reporter gen assay established. Therein, selective inhibitors for COX1 (SC58125 and COX2 (SC560 were also applied. Conclusion: Our data show (a that COX1 metabolites are involved in the regulation of renal organic anion transport(ers after I/R via the EP4 receptor and (b that this is due to transcriptional regulation of the respective transporters. As the promoter sequences cloned were of human origin and expressed in a human renal epithelial cell line we (c hypothesize that the regulatory mechanisms described after I/R is meaningful for humans as well.

  8. Brabykinin B1 Receptor Antagonism Is Beneficial in Renal Ischemia-Reperfusion Injury

    Science.gov (United States)

    Wang, Pamella H. M.; Campanholle, Gabriela; Cenedeze, Marcos A.; Feitoza, Carla Q.; Gonçalves, Giselle M.; Landgraf, Richardt G.; Jancar, Sonia; Pesquero, João B.; Pacheco-Silva, Alvaro; Câmara, Niels O. S.

    2008-01-01

    Previously we have demonstrated that bradykinin B1 receptor deficient mice (B1KO) were protected against renal ischemia and reperfusion injury (IRI). Here, we aimed to analyze the effect of B1 antagonism on renal IRI and to study whether B1R knockout or antagonism could modulate the renal expression of pro and anti-inflammatory molecules. To this end, mice were subjected to 45 minutes ischemia and reperfused at 4, 24, 48 and 120 hours. Wild-type mice were treated intra-peritoneally with antagonists of either B1 (R-954, 200 µg/kg) or B2 receptor (HOE140, 200 µg/kg) 30 minutes prior to ischemia. Blood samples were collected to ascertain serum creatinine level, and kidneys were harvested for gene transcript analyses by real-time PCR. Herein, B1R antagonism (R-954) was able to decrease serum creatinine levels, whereas B2R antagonism had no effect. The protection seen under B1R deletion or antagonism was associated with an increased expression of GATA-3, IL-4 and IL-10 and a decreased T-bet and IL-1β transcription. Moreover, treatment with R-954 resulted in lower MCP-1, and higher HO-1 expression. Our results demonstrated that bradykinin B1R antagonism is beneficial in renal IRI. PMID:18725957

  9. The protective effects of pomegranate extracts against renal ischemia-reperfusion injury in male rats

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    Ahmet A Sancaktutar

    2014-01-01

    Full Text Available Aim: To evaluate the possible protective effect of pomegranate extract (PE on rats following renal ischemia-reperfusion (I/R injury. Materials and Methods: Twenty-four Wistar rats were divided into three groups. Sham group underwent laparotomy then waited for 45 minutes without ischemia. I/R group were subjected to left renal ischemia for 45 minutes followed by 60 minutes of reperfusion. I/R + PE group were subjected to the same renal I/R as the I/R group were also given 225 mg/kg PE peroral 30 minutes prior to the ischemia. Malondialdehyde (MDA, total antioxidant capacity (TAC, total oxidant status (TOS, and oxidative stress index (OSI were determined on the blood samples and kidney tissues. Histopathological analyses were conducted on the kidney tissues. Results: Serum TAC levels were significantly decreased in I/R group when compared with S group (P = 0.001. Serum MDA levels were increased in I/R group; however, it was not statistically significant. In rat kidney tissues, TOS levels and OSI index were significantly increased after I/R injury, while TAC levels were decreased. In I/R + PE group, PE reversed the negative effects of I/R injury. PE pretreatment was effective in decreasing tubular necrosis score. Conclusion: PE pretreatment ameliorated the oxidative damage and histopathological changes occurring following renal I/R injury.

  10. Chronic exposure to zinc oxide nanoparticles increases ischemic-reperfusion injuries in isolated rat hearts

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    Milivojević, Tamara; Drobne, Damjana; Romih, Tea; Mali, Lilijana Bizjak; Marin, Irena; Lunder, Mojca; Drevenšek, Gorazd

    2016-10-01

    The use of zinc oxide nanoparticles (ZnO NPs) in numerous products is increasing, although possible negative implications of their long-term consumption are not known yet. Our aim was to evaluate the chronic, 6-week oral exposure to two different concentrations of ZnO NPs on isolated rat hearts exposed to ischemic-reperfusion injury and on small intestine morphology. Wistar rats of both sexes ( n = 18) were randomly divided into three groups: (1) 4 mg/kg ZnO NPs, (2) 40 mg/kg ZnO NPs, and (3) control. After 6 weeks of treatment, the hearts were isolated, the left ventricular pressure (LVP), the coronary flow (CF), the duration of arrhythmias and the lactate dehydrogenase release rate (LDH) were measured. A histological investigation of the small intestine was performed. Chronic exposure to ZnO NPs acted cardiotoxic dose-dependently. ZnO NPs in dosage 40 mg/kg maximally decreased LVP (3.3-fold) and CF (2.5-fold) and increased the duration of ventricular tachycardia (all P < 0.01) compared to control, whereas ZnO NPs in dosage 4 mg/kg acted less cardiotoxic. Goblet cells in the small intestine epithelium of rats, treated with 40 mg ZnO NPs/kg, were enlarged, swollen and numerous, the intestinal epithelium width was increased. Unexpectedly, ZnO NPs in both dosages significantly decreased LDH. A 6-week oral exposure to ZnO NPs dose-dependently increased heart injuries and caused irritation of the intestinal mucosa. A prolonged exposure to ZnO NPs might cause functional damage to the heart even with exposures to the recommended daily doses, which should be tested in future studies.

  11. Remote ischemic preconditioning protects against liver ischemia-reperfusion injury via heme oxygenase-1-induced autophagy.

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    Yun Wang

    Full Text Available BACKGROUND: Growing evidence has linked autophagy to a protective role of preconditioning in liver ischemia/reperfusion (IR. Heme oxygenase-1 (HO-1 is essential in limiting inflammation and preventing the apoptotic response to IR. We previously demonstrated that HO-1 is up-regulated in liver graft after remote ischemic preconditioning (RIPC. The aim of this study was to confirm that RIPC protects against IR via HO-1-mediated autophagy. METHODS: RIPC was performed with regional ischemia of limbs before liver ischemia, and HO-1 activity was inhibited pre-operation. Autophagy was assessed by the expression of light chain 3-II (LC3-II. The HO-1/extracellular signal-related kinase (ERK/p38/mitogen-activated protein kinase (MAPK pathway was detected in an autophagy model and mineral oil-induced IR in vitro. RESULTS: In liver IR, the expression of LC3-II peaked 12-24 h after IR, and the ultrastructure revealed abundant autophagosomes in hepatocytes after IR. Autophagy was inhibited when HO-1 was inactivated, which we believe resulted in the aggravation of liver IR injury (IRI in vivo. Hemin-induced autophagy also protected rat hepatocytes from IRI in vitro, which was abrogated by HO-1 siRNA. Phosphorylation of p38-MAPK and ERK1/2 was up-regulated in hemin-pretreated liver cells and down-regulated after treatment with HO-1 siRNA. CONCLUSIONS: RIPC may protect the liver from IRI by induction of HO-1/p38-MAPK-dependent autophagy.

  12. Lovastatin protects mithochondrial and renal function in kidney ischemia-reperfusion in rats Lovastatina protege a função renal e mitocondrial na isquemia/reperfusão renal em ratos

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    Silvio Tucci Junior

    2012-07-01

    Full Text Available PURPOSE: To investigate the effect of lovastatin on renal ischemia followed by reperfusion. METHODS: Thirty one Wistar rats submitted to left renal ischemia for 60 minutes followed by contralateral nephrectomy were divided into two groups: A (n =17, control, no treatment, and B (n=14, lovastatin 15 mg/kg/day p.o. ten days before ischemia. The animals were sacrificed at the end of ischemia, after 24 hours and at seven days after reperfusion. Survival, serum urea and creatinine levels and renal mitochondrial function were evaluated. RESULTS: Mortality was 29.4% in group A and 0.7% in group B. Urea and creatinine levels were increased in both groups, but the values were significantly lower in group B. Mitochondrial function showed decoupling in 83.4% of group A, as opposed to 38.4/% of group B. CONCLUSIONS: The result shows a protective action of renal function by lovastatin administered before ischemia/reperfusion. Since most of the mitochondrial fraction presented membranes with the ability to maintain ATP production in group B, stabilization of the mitochondrial membrane should be considered as part of the protective action of lovastatin on renal function in ischemia/reperfusion.OBJETIVO: Investigar a ação da lovastatina na isquemia renal seguida de reperfusão. MÉTODOS: Trinta e um ratos Wistar submetidos à isquemia renal esquerda durante 60 minutos, seguida da nefrectomia contralateral, foram distribuídos em dois grupos: A (n=17, controle, sem tratamento e B (n=14, recebendo 15 mg/Kg/dia de lovastatina via oral, durante os dez dias que antecederam a isquemia. Os animais foram mortos ao final da isquemia, e com 24 horas e sete dias após a reperfusão. Foram avaliadas a sobrevida, os valores séricos de uréia e creatinina e a função mitocondrial renal. RESULTADOS: A mortalidade foi 29,4% no grupo A e 0,7% no grupo B. Os níveis de uréia e creatinina elevaram-se nos dois grupos, mas foram significativamente menores no grupo B. No grupo

  13. Propofol Prevents Renal Ischemia-Reperfusion Injury via Inhibiting the Oxidative Stress Pathways

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    Yingjie Li

    2015-08-01

    Full Text Available Background/Aims: Renal ischemia/reperfusion injury (IRI is a risk for acute renal failure and delayed graft function in renal transplantation and cardiac surgery. The purpose of this study is to determine whether propofol could attenuate renal IRI and explore related mechanism. Methods: Male rat right kidney was removed, left kidney was subjected to IRI. Propofol was intravenously injected into rats before ischemia. The kidney morphology and renal function were analyzed. The expression of Bax, Bcl-2, caspase-3, cl-caspase-3, GRP78, CHOP and caspase-12 were detected by Western blot analysis. Results: IR rats with propofol pretreatment had better renal function and less tubular apoptosis than untreated IR rats. Propofol pretreated IR rats had lower Bax/Bcl-2 ratio and less cleaved caspase-3. The protein expression levels of GRP78, CHOP and caspase-12 decreased significantly in propofol pretreated IR rats. In vitro cell model showed that propofol significantly increased the viability of NRK-52E cells that were subjected to hypoxia/reoxygenation (H/R in a dose-dependent manner. The effect of propofol on the expression regulation of Bax, Bcl-2, caspase-3, GRP78, CHOP was consistent in both in vitro and in vivo models. Conclusion: Experimental results suggest that propofol prevents renal IRI via inhibiting oxidative stress.

  14. Pharmacokinetics of ligustrazine ethosome patch in rats and anti-myocardial ischemia and anti-ischemic reperfusion injury effect

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    Liu X

    2011-07-01

    Full Text Available Xingyan Liu1, Hong Liu1, Zhaowu Zeng2, Weihua Zhou3, Jianqiang Liu2, Zhiwei He11China-America Cancer Research Institute, Guangdong Medical College, 2Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical College, Dongguan, Guangdong, 3Yichun University, Yichun, Jiangxi, People's Republic of ChinaAbstract: The objective of this study was to investigate the pharmacokinetics of the ligustrazine ethosome patch and antimyocardial ischemia and anti-ischemic reperfusion injury effect. Male Sprague Dawley rats were divided randomly into 3 groups: Group A (intragastric ligustrazine, Group B (transdermal ligustrazine ethosome patch, and Group C (conventional transdermal ligustrazine patch. After treatment, samples of blood and of various tissues such as heart, liver, spleen, lung, kidney, brain, and muscle samples were taken at different time points. Drug concentration was measured with HPLC, and the drug concentration–time curve was plotted. Pharmacokinetic software 3p97 was applied to calculate pharmacokinetic parameters and the area under the drug concentration–time curve (AUC in various tissues. The rat model of acute myocardial ischemia was constructed with intravenous injection of pituitrin and the model of myocardial ischemia-perfusion injury was constructed by tying off the left anterior descending coronary artery of rats to observe the effect of ligustrazine ethosome patches on ischemic myocardium and ischemia-reperfusion injury. Results showed that AUC was highest in the transdermal drug delivery group of ligustrazine ethosome patch. There were significant differences in whole blood viscosity, plasma viscosity, hematocrit, red blood cell aggregation index, and deformation index between ligustrazine the ethosome patch group and ischemic control group (P < 0.01. Moreover, ligustrazine ethosome patches could reduce the scope of myocardial infarction induced by long-term ischemia. Ligustrazine ethosome patches

  15. Autofluorescence dynamics during reperfusion following long-term renal ischemia in a rat model

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    Raman, R N; Pivetti, C D; Matthews, D L; Troppmann, C; Demos, S G

    2008-02-08

    Optical properties of near-surface kidney tissue were monitored in order to assess response during reperfusion to long (20 minutes) versus prolonged (150 minutes) ischemia in an in vivo rat model. Specifically, autofluorescence images of the exposed surfaces of both the normal and the ischemic kidneys were acquired during both injury and reperfusion alternately under 355 nm and 266 nm excitations. The temporal profile of the emission of the injured kidney during the reperfusion phase under 355 nm excitation was normalized to that under 266 nm as a means to account for changes in tissue optical properties independent of ischemia as well as changes in the illumination/collection geometrical parameters in future clinical implementation of this technique using a hand-held probe. The scattered excitation light signal was also evaluated as a reference signal and found to be inadequate. Characteristic time constants were extracted using fit to a relaxation model and found to have larger mean values following 150 minutes of injury. The mean values were then compared with the outcome of a chronic survival study where the control kidney had been removed. Rat kidneys exhibiting longer time constants were much more likely to fail. This may lead to a method to assess kidney viability and predict its ability to recover in the initial period following transplantation or resuscitation.

  16. PAH clearance after renal ischemia and reperfusion is a function of impaired expression of basolateral Oat1 and Oat3

    OpenAIRE

    Bischoff, Ariane; Bucher, Michael; Gekle, Michael; Sauvant, Christoph

    2014-01-01

    Abstract Determination of renal plasma flow (RPF) by para‐aminohippurate (PAH) clearance leads to gross underestimation of this respective parameter due to impaired renal extraction of PAH after renal ischemia and reperfusion injury. However, no mechanistic explanation for this phenomenon is available. Based on our own previous studies we hypothesized that this may be due to impairment of expression of the basolateral rate limiting organic anion transporters Oat1 and Oat3. Thus, we investigat...

  17. Polyethylene glycol reduces early and long-term cold ischemia-reperfusion and renal medulla injury.

    Science.gov (United States)

    Faure, Jean Pierre; Hauet, Thierry; Han, Zeqiu; Goujon, Jean Michel; Petit, Isabelle; Mauco, Gerard; Eugene, Michel; Carretier, Michel; Papadopoulos, Vassilios

    2002-09-01

    Ischemia-reperfusion injury (IRI) after transplantation is a major cause of delayed graft function, which has a negative impact on early and late graft function and improve acute rejection. We have previously shown that polyethylene glycol (PEG) and particularly PEG 20M has a protective effect against cold ischemia and reperfusion injury in an isolated perfused pig and rat kidney model. We extended those observations to investigate the role of PEG using different doses (30g or 50g/l) added (ICPEG30 or ICPEG50) or not (IC) to a simplified preservation solution to reduce IRI after prolonged cold storage (48-h) of pig kidneys when compared with Euro-Collins and University of Wisconsin solutions. The study of renal function and medulla injury was performed with biochemical methods and proton NMR spectroscopy. Histological and inflammatory cell studies were performed after reperfusion (30-40 min) and on days 7 and 14 and weeks 4, 8, and 12. Peripheral-type benzodiazepine receptor (PBR), a mitochondrial protein involved in cholesterol homeostasis, was also studied. The results demonstrated that ICPEG30 improved renal function and reduced medulla injury. ICPEG30 also improved tubular function and strongly protect mitochondrial integrity. Post-IRI inflammation was strongly reduced in this group, particularly lymphocytes TCD4(+), PBR expression was influenced by IRI in the early period and during the development of chronic dysfunction. This study clearly shows that PEG has a beneficial effect in renal preservation and suggests a role of PBR as a marker IRI and repair processes.

  18. Protective effects of Rosa canina L fruit extracts on renal disturbances induced by reperfusion injury in rats.

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    Changizi Ashtiyani, Saeed; Najafi, Houshang; Jalalvandi, Sepeideh; Hosseinei, Fatemeh

    2013-07-01

    This study aimed to investigate the effects of Rosa canina L fruit extracts on histological damages, oxidative stress, and functional disturbances induced by bilateral renal ischemia and reperfusion. Ischemia and reperfusion were induced on the kidneys of anesthetized male Sprague-Dawley rats. The rats in the reperfusion and Rosa canina groups were administered extract solvent and Rosa canina extract, respectively. In addition, in the sham group, surgery was done without ischemia. In the last 6 hours of the reperfusion period, urine sample were collected using metabolic cage and at the end of this period, blood samples were taken from the descending aorta. The kidney tissues were collected and subjected to microscopic study for histological damages, while oxidative stress was measured by determining malondialdehyde and ferric reducing/antioxidant power levels. The comparison between the reperfusion and sham groups indicated reductions in creatinine clearance, absolute excretion of potassium, urine osmilarity, and increase in absolute excretion of sodium in the reperfusion group. These changes were less pronounced with Rosa canina fruit extract. In addition, blood creatinine and urea concentrations which increased in the reperfusion group, were significantly lower in the Rosa canina group. In this group, the degree of histological damages and the level of malondialdehyde were lower than the reperfusion group, while ferric reducing/antioxidant power level was significantly higher. The findings of this study showed that Rosa canina fruit extract possesses protective effects against kidney function disturbances, oxidative stress, and histological damages.

  19. Cardioprotective effect of the Hibiscus rosa sinensis flowers in an oxidative stress model of myocardial ischemic reperfusion injury in rat

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    Krishnamoorthy Karthikeyan K

    2006-09-01

    Full Text Available Abstract Background The present study investigates the cardioprotective effects of Hibiscus rosa sinensis in myocardial ischemic reperfusion injury, particularly in terms of its antioxidant effects. Methods The medicinal values of the flowers of Hibiscus rosa sinensis (Chinese rose have been mentioned in ancient literature as useful in disorders of the heart. Dried pulverized flower of Hibiscus rosa sinensis was administered orally to Wistar albino rats (150–200 gms in three different doses [125, 250 and 500 mg/kg in 2% carboxy methyl cellulose (CMC], 6 days per week for 4 weeks. Thereafter, rats were sacrificed; either for the determination of baseline changes in cardiac endogenous antioxidants [superoxide dismutase, reduced glutathione and catalase] or the hearts were subjected to isoproterenol induced myocardial necrosis. Results There was significant increase in the baseline contents of thiobarbituric acid reactive substances (TBARS [a measure of lipid per oxidation] with both doses of Hibiscus Rosa sinensis. In the 250 mg/kg treated group, there was significant increase in superoxide dismutase, reduced glutathione, and catalase levels but not in the 125 and 500 mg/kg treated groups. Significant rise in myocardial thiobarbituric acid reactive substances and loss of superoxide dismutase, catalase and reduced glutathione (suggestive of increased oxidative stress occurred in the vehicle treated hearts subjected to in vivo myocardial ischemic reperfusion injury. Conclusion It may be concluded that flower of Hibiscus rosa sinensis (250 mg/kg augments endogenous antioxidant compounds of rat heart and also prevents the myocardium from isoproterenol induced myocardial injury.

  20. 15d-PGJ2 Reduced Microglia Activation and Alleviated Neurological Deficit of Ischemic Reperfusion in Diabetic Rat Model

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    Lihong Huang

    2015-01-01

    Full Text Available To investigate the effect of PPARγ agonist 15d-PGJ2 treatment on the microglia activation and neurological deficit of ischemia reperfusion in diabetic rat model, adult Sprague-Dawley rats were sacrificed for the research. The rats were randomly categorized into four groups: (1 sham-operated group; (2 standard ischemia group; (3 diabetic ischemia group; (4 diabetic ischemia group with diabetes and treated with 15d-PGJ2. Compared to the sham-operated group, all the ischemic groups have significantly severer neurological deficits, more TNF-α and IL-1 expression, increased labeling of apoptotic cells, increased CD68 positive staining of brain lesion, and increased volume of infarct and cerebral edema in both 24 hours and 7 days after reperfusion. Interestingly, reduced neurological deficits, decreased TNF-α and IL-1 expression, less apoptotic cells and CD68 positive staining, and alleviated infarct and cerebral edema volume were observed when 15d-PGJ2 was intraperitoneally injected after reperfusion in diabetic ischemia group, suggesting its neuroprotective role in regulating microglia activation, which may have a therapeutic application in the future.

  1. ISCHEMIC PRECONDITIONING RELIEVES ISCHEMIA/REPERFUSION INJURY OF HIPPOCAMPUS NEURONS IN RAT BY INHIBITING p53 AND BAX EXPRESSIONSA

    Institute of Scientific and Technical Information of China (English)

    Hui-min Liu; Jing-xin Li; Lian-bi Chen

    2007-01-01

    Objective To examine whether ischemic preconditioning (IPC) can protect neuron against delayed death in CA1 subfield of hippocampus following reperfusion of a lethal ischemia in rats, and explore the role of p53 and bax in this process.Methods We examined the effect of IPC on delayed neuron death, neuron apoptosis, expressions of p53 and bax gene in the CA1 area of hippocampus in the rats using HE staining, flow cytometry, RT-PCR, and immunohistochemis-try technique.Results IPC enhanced the quantity of survival cells in the CA1 region of hippocampus (216 ±9 cells/0. 72 mm2 vs. 30 ±5 cells/0. 72 mm2, P<0. 01), decreased the percentages of apoptotic neurons of hippocampus caused by is-chemia/reperfusion (2. 06% ±0.21% vs. 4.27% ±0. 08% , P<0. 01), and weakened the expressions of p53 and bax gene of hippocampus compared with ischemia/reperrusion without IPC.Conclusion IPC can protect the neurons in the CA1 region of hippocampus against apoptosis caused by ischemia/reperfusion, and this process may be related to the reduced expressions of p53 and bax.

  2. Danhong injection attenuates cardiac injury induced by ischemic and reperfused neuronal cells through regulating arginine vasopressin expression and secretion.

    Science.gov (United States)

    Yang, Mingzhu; Orgah, John; Zhu, Jie; Fan, Guanwei; Han, Jihong; Wang, Xiaoying; Zhang, Boli; Zhu, Yan

    2016-07-01

    Ischemic stroke is associated with cardiac myocyte vulnerability through some unknown mechanisms. Arginine vasopressin (AVP) may exert considerable function in the relationship of brain damage and heart failure. Danhong injection (DHI) can protect both stroke and heart failure patients with good efficacy in clinics. The aim of this study is to investigate the mechanism of DHI in heart and brain co-protection effects to determine whether AVP plays key role in this course. In the present study, we found that both the supernatant from oxygen-glucose deprivation (OGD) and reperfused primary rat neuronal cells (PRNCs) and AVP treatment caused significant reduction in cell viability and mitochondrial activity in primary rat cardiac myocytes (RCMs). Besides, DHI had the same protective effects with conivaptan, a dual vasopressin V1A and V2 receptor antagonist, in reducing the RCM damage induced by overdose AVP. DHI significantly decreased the injury of both PRNCs and RCMs. Meanwhile, the AVP level was elevated dramatically in OGD and reperfusion PRNCs, and DHI was able to decrease the AVP expression in the injured PRNCs. Therefore, our present results suggested that OGD and reperfusion PRNCs might induce myocyte injury by elevating the AVP expression in PRNCs. The ability of DHI to reinstate AVP level may be one of the mechanisms of its brain and heart co-protection effects.

  3. A Nitric Oxide-Donor Furoxan Moiety Improves the Efficacy of Edaravone against Early Renal Dysfunction and Injury Evoked by Ischemia/Reperfusion

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    Fausto Chiazza

    2015-01-01

    Full Text Available Edaravone (5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, EDV is a free-radical scavenger reduces organ ischemic injury. Here we investigated whether the protective effects of EDV in renal ischemia/reperfusion (I/R injury may be enhanced by an EDV derivative bearing a nitric oxide- (NO- donor furoxan moiety (NO-EDV. Male Wistar rats were subjected to renal ischemia (45 minutes, followed by reperfusion (6 hours. Administration of either EDV (1.2–6–30 µmol/kg, i.v. or NO-EDV (0.3–1.2–6 µmol/kg, i.v. dose-dependently attenuated markers of renal dysfunction (serum urea and creatinine, creatinine clearance, urine flow, urinary N-acetyl-β-D-glucosaminidase, and neutrophil gelatinase-associated lipocalin/lipocalin-2. NO-EDV exerted protective effects in the dose-range 1.2–6 µmol/kg, while a higher dose (30 µmol/kg was needed to obtain protection by EDV. Both EDV and NO-EDV modulated tissue markers of oxidative stress and lipid peroxidation. NO-EDV, but not EDV, activated endothelial NO synthase (NOS and blunted I/R-induced upregulation of inducible NOS, secondary to modulation of Akt and NF-κB activation, respectively. Besides NO-EDV administration inhibited I/R-induced IL-1β, IL-18, IL-6, and TNF-α overproduction. Overall, these findings demonstrate that the NO-donor moiety contributes to the protection against early renal I/R injury and suggest that NO-donor EDV codrugs are worthy of additional study as innovative pharmacological tools.

  4. Secoisolariciresinol Diglucoside Induces Neovascularization Mediated Cardioprotection against Ischemic-Reperfusion Injury In Hypercholesterolemic Myocardium

    Science.gov (United States)

    Penumathsa, Suresh Varma; Koneru, Srikanth; Zhan, Lijun; John, Saji; Menon, Venogopal P; Prasad, Kailash; Maulik, Nilanjana

    2009-01-01

    Background Hypercholesterolemia (HC) induced endothelial cell dysfunction and decreased endothelial nitric oxide formation result in impaired angiogenesis & subsequent cardiovascular disorders. Therapeutic angiogenesis is known to be a novel strategy for treatment of those patients with ischemic heart disease. We have shown that secoisolariciresinol diglucoside (SDG) is angiogenic & cardioprotective against myocardial ischemia. In the present study we examined the efficacy of SDG in a hypercholesterolemic myocardial infarction (MI) model. Methods The rats were maintained on a normal and high cholesterol diet (2%) for 8 weeks followed by oral administration of SDG (20mg/kg) for 2 weeks. The rats were divided into 4 groups (n=12 in each): Control (C); SDG control (SDG); HC; & HC + SDG (HSDG). Isolated hearts subjected to 30 min of global ischemia followed by 120 min of reperfusion were used to measure the cardiac functions, infarct size & examine the protein expression profile. After treatment MI was induced by ligating the left anterior descending artery. Echocardiographic parameters were examined 30 days after MI. Results Significant reduction in total cholesterol, LDL-cholesterol, triglycerides and increase in HDL-cholesterol levels were observed in HSDG as compared to HC. Decreased infarct size was observed in the HSDG group (43%) compared to the HC (54%). Increased phosphorylation of endothelial nitric oxide synthase (p-eNOS) (3.1 fold), Vascular endothelial growth factor (1.9 fold) and Heme Oxygenase-1(2.3 fold) was observed in the HSDG group as compared to the HC group. Significant improvement in left ventricular functions was also observed in the HSDG group as evidenced by increased ejection fraction (55 vs 45%), fractional shortening (28 vs 22%) & decreased left ventricular inner diameter in systole (8 vs 6 mm) in HSDG compared to HC. Moreover, MI model has shown increased capillary density (2531 vs 1901) and arteriolar density (2.6 vs 1.8) in SDG treated

  5. PARP Inhibition Attenuates Histopathological Lesion in Ischemia/Reperfusion Renal Mouse Model after Cold Prolonged Ischemia

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    Raimundo M. G. del Moral

    2013-01-01

    Full Text Available We test the hypothesis that PARP inhibition can decrease acute tubular necrosis (ATN and other renal lesions related to prolonged cold ischemia/reperfusion (IR in kidneys preserved at 4°C in University of Wisconsin (UW solution. Material and Methods. We used 30 male Parp1+/+ wild-type and 15 male Parp10/0 knockout C57BL/6 mice. Fifteen of these wild-type mice were pretreated with 3,4-dihydro-5-[4-(1-piperidinylbutoxyl]-1(2H-isoquinolinone (DPQ at a concentration of 15 mg/kg body weight, used as PARP inhibitor. Subgroups of mice were established (A: IR 45 min/6 h; B: IR + 48 h in UW solution; and C: IR + 48 h in UW solution plus DPQ. We processed samples for morphological, immunohistochemical, ultrastructural, and western-blotting studies. Results. Prolonged cold ischemia time in UW solution increased PARP-1 expression and kidney injury. Preconditioning with PARP inhibitor DPQ plus DPQ supplementation in UW solution decreased PARP-1 nuclear expression in renal tubules and renal damage. Parp10/0 knockout mice were more resistant to IR-induced renal lesion. In conclusion, PARP inhibition attenuates ATN and other IR-related renal lesions in mouse kidneys under prolonged cold storage in UW solution. If confirmed, these data suggest that pharmacological manipulation of PARP activity may have salutary effects in cold-stored organs at transplantation.

  6. Effects of Acetyl-L-Carnitine on Cardiac Arrhythmias and Infarct Size in Ischemic-Reperfused Isolated Rat Heart

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    Moslem Najafi

    2010-01-01

    Full Text Available This study aimed to examine whether acetyl-L-carnitine (ALC was able to reduce cardiac arrhythmias and infarct size in the ischemic-reperfused isolated rat heart.Materials and MethodsThe isolated hearts were mounted on a Langendorff apparatus then perfused by a modified Krebs-Henseleit solution during 30 min regional ischemia and 120 min reperfusion (control or by enriched Krebs solution with 0.375, 0.75, 1.5 and 3 mM of ALC (treatment groups. The ECGs were recorded and analyzed to determine cardiac arrhythmias. The infarct size was determined by using a computerized planimetry package.ResultsDuring ischemia, all used concentrations of ALC decreased number and duration of ventricular tachycardia (VT, total number of ventricular ectopic beats (VEBs (P<0.01, incidence of total ventricular fibrillation (VF and the time spent for reversible VF (P<0.05. At the reperfusion phase, duration of VT, incidence of total VF and reversible VF were significantly lowered by ALC (P<0.05. In addition, infarct size significantly was decreased in all treated groups. In the control group, the infarct size was 23±3.1%, however, ALC (0.375, 0.75 and 3 mM reduced it to 8.7±2.3, 5.3±1.4, and 8±2.9%, respectively (P<0.01. ConclusionConsidering the results, it may be concluded that ALC has protective effects against cardiac ischemia-reperfusion (I/R injuries by reduction of infarct size and arrhythmias in isolated rat heart. Among the potential cardioprotective mechanisms for ALC, increase in glucose oxidation and resulting reduced lactate production, reduction of toxic fatty acid metabolites and removing free radicals from the myocytes are more relevant.

  7. PAH clearance after renal ischemia and reperfusion is a function of impaired expression of basolateral Oat1 and Oat3.

    Science.gov (United States)

    Bischoff, Ariane; Bucher, Michael; Gekle, Michael; Sauvant, Christoph

    2014-02-01

    Determination of renal plasma flow (RPF) by para-aminohippurate (PAH) clearance leads to gross underestimation of this respective parameter due to impaired renal extraction of PAH after renal ischemia and reperfusion injury. However, no mechanistic explanation for this phenomenon is available. Based on our own previous studies we hypothesized that this may be due to impairment of expression of the basolateral rate limiting organic anion transporters Oat1 and Oat3. Thus, we investigated this phenomenon in a rat model of renal ischemia and reperfusion by determining PAH clearance, PAH extraction, PAH net secretion, and the expression of rOat1 and rOat3. PAH extraction was seriously impaired after ischemia and reperfusion which led to a threefold underestimation of RPF when PAH extraction ratio was not considered. PAH extraction directly correlated with the expression of basolateral Oat1 and Oat3. Tubular PAH secretion directly correlated with PAH extraction. Consequently, our data offer an explanation for impaired renal PAH extraction by reduced expression of the rate limiting basolateral organic anion transporters Oat1 and Oat3. Moreover, we show that determination of PAH net secretion is suitable to correct PAH clearance for impaired extraction after ischemia and reperfusion in order to get valid results for RPF.

  8. Efeito da cinesioterapia na lesão isquêmica e reperfusão em ratos Effects of kinesiotherapy in ischemic lesion and reperfusion in rats

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    Flavia Moscardini

    2012-01-01

    Full Text Available OBJETIVO: Verificar o efeito da cinesioterapia na funcionalidade do membro pélvico de ratos após lesão isquêmica e reperfusão. MÉTODOS: Foram utilizados 10 ratos, divididos em dois grupos, GI (controle e GII (cinesioterapia. Todos os animais foram submetidos à isquemia por um período de três horas, seguido de reperfusão tecidual. No Grupo GII foi realizado cinesioterapia sistêmica (natação não resistida em três sessões semanais de 50 minutos durante quatro semanas, enquanto que no grupo GI os animais permaneceram em repouso. A análise funcional do comportamento motor foi realizada semanalmente. Posteriormente, os animais foram mortos e retirados os músculos sóleo, gastrocnêmio e nervo ciático para análise histopatológica. RESULTADOS: Houve uma recuperação significativa do comportamento motor com o tratamento cinesioterapêutico ao longo das quatro semanas de tratamento. No entanto, na avaliação histológica os tecidos não mostraram alterações morfológicas de lesão e reparação celular. CONCLUSÃO: Não foi possível afirmar que o exercício mostrou-se eficiente na reparação celular, pois, tanto no grupo controle como no experimental, não apresentou diferença histológica. Por outro lado, a cinesioterapia sistêmica apresentou um efeito benéfico na reabilitação funcional após isquemia e reperfusão. Nível de Evidência III, Estudo Caso-Controle.OBJECTIVE: To investigate the effect of kinesiotherapy on the functionality of the pelvic limb of rats after ischemic and reperfusion injury. METHODS: 10 rats were divided into two groups, GI (control and GII (kinesiotherapy. All the animals underwent ischemia for a period of three hours, followed by tissue reperfusion. In Group GII, non-resistive systemic kinesiotherapy was performed (swimming in three weekly sessions of 50 minutes, over a period of four weeks, while the GI animals remained at rest. Functional analysis of motor behavior was evaluated weekly. The

  9. Effect of terminal warm reperfusion (hot shot and remote ischemic preconditioning, either separately or combined, on myocardial recovery in adult cardiac surgery

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    Mohamed Elgariah

    2017-09-01

    Conclusions: Both remote ischemic preconditioning and terminal hot shot reperfusion before removal of the aortic cross clamping improved outcome of on-pump adult cardiac surgery patients. There was a significant effect on the in-hospital mortality and there were fewer incidences of arrhythmias and less requirement for postoperative inotropic support with this technique.

  10. Melatonin treatment against remote organ injury induced by renal ischemia reperfusion injury in diabetes mellitus.

    Science.gov (United States)

    Fadillioglu, Ersin; Kurcer, Zehra; Parlakpinar, Hakan; Iraz, Mustafa; Gursul, Cebrail

    2008-06-01

    Oxidative stress may have a role in liver damage after acute renal injury due to various reasons such as ischemia reperfusion (IR). Diabetes mellitus (DM) is an important disease for kidneys and may cause nephropathy as a long term complication. The aim of this study was to investigate protective effect of melatonin, a potent antioxidant, against distant organ injury on liver induced by renal IR in rats with or without DM. The rats were divided into six groups: control (n=7), DM (n=5), IR (n=7), DM+IR (n=7), melatonin+IR (Mel+IR) (melatonin, 4 mg/ kg during 15 days) (n=7), and Mel+DM+IR groups (n=7). Diabetes developed 3 days after single i.p. dose of 45 mg/kg streptozotocin. After 15 day, the left renal artery was occluded for 30 min followed 24 h of reperfusion in IR performed groups. DM did not alter oxidative parameters alone in liver tissue. The levels of malondialdehyde, protein carbonyl and nitric oxide with activities of xanthine oxidase and myeloperoxidase were increased in liver tissues of diabetic and non-diabetic IR groups. Nitric oxide level in DM was higher than control. The activities of catalase and superoxide dismutase were increased in IR groups in comparison with control and DM. ALT and AST levels were higher in IR and DM+IR groups than control and DM. Melatonin treatment reversed all these oxidant and antioxidant parameters to control values as well as serum liver enzymes. We concluded that renal IR may affect distant organs such as liver and oxidative stress may play role on this injury, but DM has not an effect on kidney induced distant organ injury via oxidant stress. Also, it was concluded that melatonin treatment may prevent liver oxidant stress induced by distant injury of kidney IR.

  11. Role of Mitochondrial Enzymes and Sarcoplasmic ATPase in Cardioprotection Mediated by Aqueous Extract of Desmodium gangeticum (L) DC Root on Ischemic Reperfusion Injury.

    Science.gov (United States)

    Kurian, G A; Paddikkala, J

    2010-11-01

    The present study investigate the protective effect of aqueous root extract of Desmodium gangeticum in preserving mitochondrial and sarcoplasmic ATPase during ischemia reperfusion injury. The isolated rat hearts in both drug and control group were subjected to warm ischemia (37°), followed by reperfusion with the Langendorff perfusion system. The aqueous root extract of Desmodium gangeticum (L) at a dose of 50 mg/kg body weight was found to be effective in the rat heart for the management of ischemic reperfusion injury. Physiological parameters were significantly (PDesmodium gangeticum treated rat heart. These results suggest that Desmodium gangeticum aqueous root extract can preserve the mitochondrial and sarcoplasmic ATPase in the myocardium, resulting in the improvement of cardiac function after ischemia reperfusion injury.

  12. Cardioprotective Effect of Angiotensin Ⅱ Receptor Antagonist on Perfused Ischemic Reper-fusion Injury of Whole Isolated Rat Hearts

    Institute of Scientific and Technical Information of China (English)

    徐延敏; 黄体钢; 陈元禄; 李广平

    2003-01-01

    Objectives Investigated the cardioprotective and mechanisms of losartan onwhole isolated ischemic reperfused rat heart. Meth-ods Langendorff perfused systems was used to in-vestigate losartan effect on whole isolated rat hearts inCPK, LDH, MDA, SOD, ang Ⅱ and arrhythmia. Re-sults Losartan decreased incidence of arrhythmia,improved atrial ventricular block recovery in reperfu-sion period, during ischemic period, CPK and LDH inI/R group increased significantly compared with con-trol group, 51.33±27.02 vs 22.42±13.33, 31.80±4.56 vs 22.28 ± 15.96, respectively, but greatlydecreased in losartan group compared with I/R group,23.90±21.74 vs 51.33±27.02 and 11.50±13.20vs 31.80 ± 4. 56, respectively. During reperfusion pe-riod CPK, LDH increased significantly in I/R groupcompared with control group, 49.11 ± 20.63 vs 12.14±5.92 and 28.70±4.69 vs 23.10±21.38, re-spectively, but decreased greatly in losartan groupcompared with I/R group, 39.40 ± 9.60 vs 49.11 ±20.63 and 14.50±13.75 vs 28.70±4.69. Thecontent of MDA, ang Ⅱ in I/R group myocytes ishigher than control group's , 26. ±9. 25 vs 17.2 ±3.37 and 8.43±3.81 vs 4. 80±0.20. However thecontent of SOD in two groups has no significantlychange, 148. 20 ± 8. 72 vs 145.08±6.82. the con-tent of MDA in losartan group myocardial tissue ismuch lower than control group, 15.92±4.05 vs26.80± 9.25 and the content of ang Ⅱ in losartangroup myocardial tissue is much higher than I/Rgroup, 12.44 ± 6.09 vs 8.43 ± 3.21. The departmentof cardiology of second hospital of Tianjin medical u-niversity Tianjin 300211 However, SOD has nosignificant change in two groups, 143.47 ±7.91 vs145.08 ± 6.82. Conclusions Losartan against is-chemic-reperfusion injury of whole isolated rathearts, those beneficial effects are mediate primarily bythe inhibited of angiotensin Ⅱ binding with its receptorand inhibited oxygen free radical scavenging potential.

  13. Mycophenolate mofetil affects monocyte Toll-like receptor 4 signaling during mouse renal ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yan-xia; ZHANG Jian-rong; WANG Zhi-gang

    2013-01-01

    Background Mycophenolate mofetil (MMF) has been used to prevent transplant rejection for many years and has been shown to have protective effects against renal failure.The objective was to investigate the effect of MMF on monocyte Toll-like receptor 4 (TLR4) signaling in the early stages of renal ischemia/reperfusion injury (IRI) of mice.Methods Sixty BALB/C mice were randomly divided into two groups:an IRI group,in which renal IRI was induced by clamping the renal pedicles for 45 minutes,and an MMF group,in which MMF was given (40 mg·kg-1·d-1,intraperitoneally) from 2 days before renal IRI.The plasma creatinine level and renal tissue damage of each group mice were observed 6,12,24,and 48 hours after reperfusion.The concentration of plasma high-mobility group box 1 (HMGB-1) (TLR4 ligand),interleukin 6 (IL-6),monocyte chemoattractant protein-1 (MCP-1),and tumor necrosis factor α (TNF-α) and the expression of TLR-4 on monocytes were determined.Results The plasma creatinine concentration in the MMF group was lower compared to the IRI group (after reperfusion of 6,12,24,or 48 hours,P <0.05).Pathological analysis showed that the renal damage was slighter,TLR-4 expression was reduced (after reperfusion of 6,12,24,or 48 hours,P <0.05),and the concentration of cytokines in the plasma was lower (P <0.05) in the MMF group.No differences in the concentrations of HMGB-1 were observed (P >0.05).Conclusion Monocyte TLR4 signaling is important in the early stage of kidney IRI,but MMF can inhibit it and improve renal function.

  14. Hepatic ischemic preconditioning increases portal vein lfow in experimental liver ischemia reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Estela RR Figueira; Joel A Rocha-Filho; Mauro Nakatani; Marcelo FS Buto; Eduardo R Tatebe; Vitor O Andre

    2014-01-01

    BACKGROUND: Ischemic preconditioning (IPC) has been shown to decrease liver injury and to increase hepatic microvascular perfusion after liver ischemia reperfusion. This study aimed to evaluate the effects of IPC on hemodynamics of the portal venous system. METHODS: Thirty-two  rats  were  randomized  into  two groups: IPC group and control group. The rats of the IPC group underwent IPC by 10 minutes of liver ischemia followed by 10 minutes of reperfusion before liver ischemia, and the rats of the control group were subjected to 60 minutes of partial liver ischemia. Non-ischemic lobes were resected immediately after reperfusion. The animals were studied at 4 hours and 12 hours after reperfusion. Mean arterial pressure, heart rate, portal vein lfow and pressure were analyzed. Blood was collected for the determination of the levels of aspartate aminotransferase, alanine aminotransferase, calcium, lactate, pH, bicarbonate, and base excess. RESULTS: IPC increased the mean portal vein lfow at 4 hours and 12 hours after reperfusion. IPC recovered 78% of the mean portal vein lfow at 12 hours after reperfusion. IPC decreased the levels of aspartate aminotransferase, alanine aminotransferase and  lactate,  and  increased  the  levels  of  ionized  calcium, bicarbonate and base excess at 12 hours after reperfusion. CONCLUSIONS: This study demonstrated that IPC increases portal  vein  lfow  and  enhances  hepatoprotective  effects  in liver  ischemia  reperfusion.  The  better  recovery  of  portal vein lfow after IPC may be correlated

  15. Putative role of ischemic postconditioning in a rat model of limb ischemia and reperfusion: involvement of hypoxia-inducible factor-1? expression

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    T. Wang

    2014-09-01

    Full Text Available Hypoxia-inducible factor-1α (HIF-1α is one of the most potent angiogenic growth factors. It improves angiogenesis and tissue perfusion in ischemic skeletal muscle. In the present study, we tested the hypothesis that ischemic postconditioning is effective for salvaging ischemic skeletal muscle resulting from limb ischemia-reperfusion injury, and that the mechanism involves expression of HIF-1α. Wistar rats were randomly divided into three groups (n=36 each: sham-operated (group S, hindlimb ischemia-reperfusion (group IR, and ischemic postconditioning (group IPO. Each group was divided into subgroups (n=6 according to reperfusion time: immediate (0 h, T0, 1 h (T1, 3 h (T3, 6 h (T6, 12 h (T12, and 24 h (T24. In the IPO group, three cycles of 30-s reperfusion and 30-s femoral aortic reocclusion were carried out before reperfusion. At all reperfusion times (T0-T24, serum creatine kinase (CK and lactate dehydrogenase (LDH activities, as well as interleukin (IL-6, IL-10, and tumor necrosis factor-α (TNF-α concentrations, were measured in rats after they were killed. Histological and immunohistochemical methods were used to assess the skeletal muscle damage and HIF-1α expression in skeletal muscle ischemia. In groups IR and IPO, serum LDH and CK activities and TNF-α, IL-6, and IL-10 concentrations were all significantly increased compared to group S, and HIF-1α expression was up-regulated (P<0.05 or P<0.01. In group IPO, serum LDH and CK activities and TNF-α and IL-6 concentrations were significantly decreased, IL-10 concentration was increased, HlF-1α expression was down-regulated (P<0.05 or P<0.01, and the pathological changes were reduced compared to group IR. The present study suggests that ischemic postconditioning can reduce skeletal muscle damage caused by limb ischemia-reperfusion and that its mechanisms may be related to the involvement of HlF-1α in the limb ischemia-reperfusion injury-triggered inflammatory response.

  16. Putative role of ischemic postconditioning in a rat model of limb ischemia and reperfusion: involvement of hypoxia-inducible factor-1α expression

    Energy Technology Data Exchange (ETDEWEB)

    Wang, T. [Department of Anesthesiology, Shuyang People' s Hospital, JiangSu (China); Zhou, Y.T. [Department of General Surgery, Shuyang People' s Hospital, JiangSu (China); Chen, X.N. [Institute of Pathophysiology, School of Basic Medical Sciences, LanZhou University, Lanzhou, Gansu (China); Zhu, A.X. [Department of Pharmacy, Shuyang People' s Hospital, JiangSu (China)

    2014-07-25

    Hypoxia-inducible factor-1α (HIF-1α) is one of the most potent angiogenic growth factors. It improves angiogenesis and tissue perfusion in ischemic skeletal muscle. In the present study, we tested the hypothesis that ischemic postconditioning is effective for salvaging ischemic skeletal muscle resulting from limb ischemia-reperfusion injury, and that the mechanism involves expression of HIF-1α. Wistar rats were randomly divided into three groups (n=36 each): sham-operated (group S), hindlimb ischemia-reperfusion (group IR), and ischemic postconditioning (group IPO). Each group was divided into subgroups (n=6) according to reperfusion time: immediate (0 h, T{sub 0}), 1 h (T{sub 1}), 3 h (T{sub 3}), 6 h (T{sub 6}), 12 h (T{sub 12}), and 24 h (T{sub 24}). In the IPO group, three cycles of 30-s reperfusion and 30-s femoral aortic reocclusion were carried out before reperfusion. At all reperfusion times (T{sub 0}-T{sub 24}), serum creatine kinase (CK) and lactate dehydrogenase (LDH) activities, as well as interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α) concentrations, were measured in rats after they were killed. Histological and immunohistochemical methods were used to assess the skeletal muscle damage and HIF-1α expression in skeletal muscle ischemia. In groups IR and IPO, serum LDH and CK activities and TNF-α, IL-6, and IL-10 concentrations were all significantly increased compared to group S, and HIF-1α expression was up-regulated (P<0.05 or P<0.01). In group IPO, serum LDH and CK activities and TNF-α and IL-6 concentrations were significantly decreased, IL-10 concentration was increased, HlF-1α expression was down-regulated (P<0.05 or P<0.01), and the pathological changes were reduced compared to group IR. The present study suggests that ischemic postconditioning can reduce skeletal muscle damage caused by limb ischemia-reperfusion and that its mechanisms may be related to the involvement of HlF-1α in the limb ischemia-reperfusion injury

  17. Ciclosporin Does Not Influence Bone Marrow-Derived Cell Differentiation to Myofibroblasts Early after Renal Ischemia/Reperfusion

    NARCIS (Netherlands)

    Broekema, Martine; Harmsen, Martin C.; Koerts, Jasper A.; van Kooten, Theo G.; Uges, Donald R. A.; Petersen, Arjen H.; van Luyn, Marja J. A.; Navis, Gerjan; Popa, Eliane R.

    2009-01-01

    Background: Ischemia/reperfusion injury (IRI) is a risk factor for the development of interstitial fibrosis. Previously we had shown that after renal IRI, bone marrow-derived cells (BMDC) can differentiate to interstitial myofibroblasts. Here we hypothesized that the immunosuppressant ciclosporin A

  18. Improved resistance to ischemia and reperfusion, but impaired protection by ischemic preconditioning in patients with type 1 diabetes mellitus: a pilot study

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    Engbersen Richard

    2012-10-01

    Full Text Available Abstract Background In patients with type 1 diabetes mellitus (T1DM, cardiovascular events are more common, and the outcome following a myocardial infarction is worse than in nondiabetic subjects. Ischemic or pharmacological preconditioning are powerful interventions to reduce ischemia reperfusion (IR-injury. However, animal studies have shown that the presence of T1DM can limit these protective effects. Therefore, we aimed to study the protective effect of ischemic preconditioning in patients with T1DM, and to explore the role of plasma insulin and glucose on this effect. Methods 99mTechnetium-annexin A5 scintigraphy was used to detect IR-injury. IR-injury was induced by unilateral forearm ischemic exercise. At reperfusion, Tc-annexin A5 was administered, and IR-injury was expressed as the percentage difference in radioactivity in the thenar muscle between the experimental and control arm 4 hours after reperfusion. 15 patients with T1DM were compared to 21 nondiabetic controls. The patients were studied twice, with or without ischemic preconditioning (10 minutes of forearm ischemia and reperfusion. Patients were studied in either normoglycemic hyperinsulinemic conditions (n = 8 or during hyperglycemic normoinsulinemia (n = 7. The controls were studied once either with (n = 8 or without (n = 13 ischemic preconditioning. Results Patients with diabetes were less vulnerable to IR-injury than nondiabetic healthy controls (12.8 ± 2.4 and 11.0 ± 5.1% versus 27.5 ± 4.5% in controls; p  Conclusions Patients with T1DM are more tolerant to forearm IR than healthy controls in our experimental model. The efficacy of ischemic preconditioning to limit IR-injury, however, is reduced by acute hyperglycemia. Trial Registration The study is registered at www.clinicaltrials.gov (NCT00184821

  19. Microvesicles derived from endothelial progenitor cells protect the kidney from ischemia-reperfusion injury by microRNA-dependent reprogramming of resident renal cells.

    Science.gov (United States)

    Cantaluppi, Vincenzo; Gatti, Stefano; Medica, Davide; Figliolini, Federico; Bruno, Stefania; Deregibus, Maria C; Sordi, Andrea; Biancone, Luigi; Tetta, Ciro; Camussi, Giovanni

    2012-08-01

    Endothelial progenitor cells are known to reverse acute kidney injury by paracrine mechanisms. We previously found that microvesicles released from these progenitor cells activate an angiogenic program in endothelial cells by horizontal mRNA transfer. Here, we tested whether these microvesicles prevent acute kidney injury in a rat model of ischemia-reperfusion injury. The RNA content of microvesicles was enriched in microRNAs (miRNAs) that modulate proliferation, angiogenesis, and apoptosis. After intravenous injection following ischemia-reperfusion, the microvesicles were localized within peritubular capillaries and tubular cells. This conferred functional and morphologic protection from acute kidney injury by enhanced tubular cell proliferation, reduced apoptosis, and leukocyte infiltration. Microvesicles also protected against progression of chronic kidney damage by inhibiting capillary rarefaction, glomerulosclerosis, and tubulointerstitial fibrosis. The renoprotective effect of microvesicles was lost after treatment with RNase, nonspecific miRNA depletion of microvesicles by Dicer knock-down in the progenitor cells, or depletion of pro-angiogenic miR-126 and miR-296 by transfection with specific miR-antagomirs. Thus, microvesicles derived from endothelial progenitor cells protect the kidney from ischemic acute injury by delivering their RNA content, the miRNA cargo of which contributes to reprogramming hypoxic resident renal cells to a regenerative program.

  20. Effect of glutamine on the total antioxidant system of rats subjected to renal ischemia and reperfusion Efeito da glutamina no sistema antioxidante total de ratos submetidos a isquemia e reperfusão renal

    Directory of Open Access Journals (Sweden)

    Valter Torezan Gouvêa Junior

    2011-12-01

    Full Text Available PURPOSE: To evaluate the protective effects of glutamine administered before renal ischemia-reperfusion on plasma antioxidant protection, and lung and renal tissue injury. METHODS: 33 rats underwent right nephrectomy. On the eighth postoperative day, animals were randomized into three groups (n=11: glutamine, control and sham. Each group of animals received, by gavage, a particular diet for 7 days. On day 14 following nephrectomy, the animals were subjected to left renal ischemia-reperfusion. After this, blood samples were collected and the animals were killed. At necropsy the kidney and lung were removed for histology. RESULTS: The levels of total antioxidant capacity were higher in the glutamine group and control group compared with the sham group. The levels of glutathione peroxidase in both the sham and glutamine groups were higher when compared with the control group (pOBJETIVO: Avaliar os efeitos na proteção antioxidante plasmática e na lesão tecidual renal e pulmonar da glutamina oral administrada precedendo a isquemia/ reperfusão renal. MÉTODOS: Trinta e três ratos foram submetidos à nefrectomia à direita. No oitavo dia de pós-operatório, os animais foram randomizados em três grupos (n=11: glutamina, controle e sham. Cada grupo de animal recebeu por gavagem uma dieta distinta por sete dias. Ao final do 14º dia da nefrectomia procedeu-se a isquemia renal esquerda e posterior reperfusão. A seguir procedeu-se a coleta de sangue, eutanásia e retirada do rim e pulmões para análise histológica. RESULTADOS: Os níveis de capacidade antioxidante total foram maiores no grupo glutamina e grupo controle em relação ao grupo sham. Os níveis de glutationa peroxidase nos grupos sham e glutamina foram mais elevados quando comparados com o grupo controle (p<0,05. A dosagem de superóxido dismutase foi maior no grupo sham quando comparado com os grupos glutamina e controle. Não houve diferença na análise histológica do rim e pulm

  1. Activated Notch1 reduces myocardial ischemia reperfusion injury in vitro during ischemic postconditioning by crosstalk with the RISK signaling pathway

    Institute of Scientific and Technical Information of China (English)

    ZHOU Xue-liang; WAN Li; LIU Ji-chun

    2013-01-01

    Background Ischemic postconditioning (IPost),able to significantly attenuate myocardial ischemia reperfusion injury,is dependent on RISK signaling.Studies have shown that Notch signaling repairs damaged myocardium,and this study aimed to investigate the effect of Notch signaling in myocardial IPost.Methods We used H9c2 cells to establish the myocardial IPost and Hypoxia/Reoxygenation (H/R) model in vitro,which were randomly divided into control,H/R,IPost,Hepatocyte growth factor (HGF)+IPost and DAPT+IPost,N1ICD+IPost,miRNA+lPost,and Mock treatment groups.The myocardial cell viability was assessed by MTT,the cell apoptosis was detected using Annexin V/PI double staining and flow cytometry analyses.The expression of N1ICD,Hes1,PTEN Phospho-Akt/Akt,Phospho-GSK-3β/GSK-3β were detected by Western blotting.Finally,we assessed the changes in Ψm using the potential-sensitive dye JC-1 and measured using flow cytometry analyses.Results The Notch1 signaling is activated by HGF and ectopic expression of N1ICD during myocardial IPost,which increased myocardial cell viability,prevented cardiomyocyte apoptosis,and reduced loss of the mitochondrial membrane potential.However,myocardial ischemia reperfusion injury was increased in IPost when Notch1 signaling was inhibited using DAPT or with knockdown by Notch1-miRNA.Western blotting found that PTEN was down-regulated by Hes1 when Notch1 was activated,which consequently promoted Akt and GSK-3β phosphorylation.Conclusions Notch1 crosstalk with RISK signaling may be dependent on PTEN,which plays a cardioprotective role during IPost.This mechanism could provide a promising therapeutic target for the treatment of ischemic heart disease.

  2. Enhanced nitric oxide-mediated autophagy contributes to the hepatoprotective effects of ischemic preconditioning during ischemia and reperfusion.

    Science.gov (United States)

    Shin, Jun-Kyu; Kang, Jung-Woo; Lee, Sun-Mee

    2016-08-31

    Ischemic preconditioning (IPC) protects against liver ischemia/reperfusion (I/R) injury. Autophagy is an essential cytoprotective system that is rapidly activated by multiple stressors. Nitric oxide (NO) acts as an inducer of IPC. We examined the impact of autophagy in liver IPC and its regulation by NO. Male C57BL/6 mice were subjected to 60 min of hepatic ischemia followed by 6 h of reperfusion. IPC was achieved for 10 min of ischemia followed by 10 min of reperfusion prior to sustained ischemia. N(ω)-Nitro-l-arginine methyl ester (L-NAME, 15 mg/kg, i.v., all NOS inhibitor) and aminoguanidine (AG, 10 mg/kg, i.v., iNOS inhibitor) were injected 10 min before IPC. SB203580 (10 mg/kg, i.p., p38 inhibitor) was injected 30 min before IPC. I/R increased serum alanine aminotransferase activity. IPC attenuated this increase, which was abolished by L-NAME, but not AG. Microtubule-associated protein-1 light chain 3-II levels increased and p62 protein levels decreased after I/R; these changes were augmented by IPC and abolished by L-NAME. I/R increased liver protein expression of autophagy-related protein (Atg)12-Atg5 complex and lysosome-associated membrane protein-2. IPC augmented the expression of these proteins, which were abolished by L-NAME, but not AG. IPC also augmented the level of phosphorylated p38 MAPK induced by I/R and this phosphorylation was abolished by L-NAME. Our findings suggest that IPC-mediated NO protects against I/R-induced liver injury by enhancing autophagic flux.

  3. Effects of sirolimus alone or in combination with cyclosporine A on renal ischemia/reperfusion injury

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    B.J. Pereira

    2010-08-01

    Full Text Available Calcineurin inhibitors exacerbate ischemic injury in transplanted kidneys, but it is not known if sirolimus protects or exacerbates the transplanted kidney from ischemic injury. We determined the effects of sirolimus alone or in combination with cyclosporin A (CsA on oxygenated and hypoxic/reoxygenated rat proximal tubules in the following in vitro groups containing 6-9 rats per group: sirolimus (10, 50, 100, 250, 500, and 1000 ηg/mL; CsA (100 µg/mL; sirolimus (50 and 250 ηg/mL + CsA (100 µg/mL; control; vehicle (20% ethanol. For in vivo studies, 3-week-old Wistar rats (150-250 g were submitted to left nephrectomy and 30-min renal artery clamping. Renal function and histological evaluation were performed 24 h and 7 days after ischemia (I in five groups: sham, I, I + SRL (3 mg·kg-1·day-1, po, I + CsA (3 mg·kg-1·day-1, sc, I + SRL + CsA. Sirolimus did not injure oxygenated or hypoxic/reoxygenated proximal tubules and did not potentiate the tubular toxic effects of CsA. Neither drug affected the glomerular filtration rate (GFR at 24 h. GFR was reduced in CsA-treated rats on day 7 (0.5 ± 0.1 mL/min but not in rats receiving sirolimus + CsA (0.8 ± 0.1 mL/min despite the reduction in renal blood flow (3.9 ± 0.5 mL/min. Acute tubular necrosis regeneration was similar for all groups. Sirolimus alone was not toxic and did not enhance hypoxia/reoxygenation injury or CsA toxicity to proximal tubules. Despite its hemodynamic effects, sirolimus protected post-ischemic kidneys against CsA toxicity.

  4. PET Demonstrates Functional Recovery after Treatment by Danhong Injection in a Rat Model of Cerebral Ischemic-Reperfusion Injury.

    Science.gov (United States)

    Wang, Zefeng; Song, Fahuan; Li, Jinhui; Zhang, Yuyan; He, Yu; Yang, Jiehong; Zhou, Huifen; Zhao, Tao; Fu, Wei; Xing, Panke; Wan, Haitong; Tian, Mei; Zhang, Hong

    2014-01-01

    This study aimed to investigate neuroprotection of Danhong injection (DHI) in a rat model of cerebral ischemia using (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET). Method. Rats were divided into 5 groups: sham group, ischemia-reperfusion untreated (IRU) group, DHI-1 group (DHI 1 mL/kg/d), DHI-2 group (DHI 2 mL/kg/d), and DHI-4 group (DHI 4 mL/kg/d). AII the treated groups were intraperitoneally injected with DHI daily for 14 days. The therapeutic effects in terms of cerebral infarct volume, neurological function, and cerebral glucose metabolism were evaluated. Expression of TNF-α and IL-1β was detected with enzyme-linked immunosorbent assay (ELISA). Levels of mature neuronal marker (NeuN), glial marker (GFAP), vascular density factor (vWF), and glucose transporter 1 (GLUT1) were assessed by immunohistochemistry. Results. Compared with the IRU group, rats treated with DHI showed dose dependent reductions in cerebral infarct volume and levels of proinflammatory cytokines, improvement of neurological function, and recovery of cerebral glucose metabolism. Meanwhile, the significantly increased numbers of neurons, gliocytes, and vessels and the recovery of glucose utilization were found in the peri-infarct region after DHI treatment using immunohistochemical analysis. Conclusion. This study demonstrated the metabolic recovery after DHI treatment by micro-PET imaging with (18)F-FDG and the neuroprotective effects of DHI in a rat model of cerebral ischemic-reperfusion injury.

  5. PET Demonstrates Functional Recovery after Treatment by Danhong Injection in a Rat Model of Cerebral Ischemic-Reperfusion Injury

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    Zefeng Wang

    2014-01-01

    Full Text Available This study aimed to investigate neuroprotection of Danhong injection (DHI in a rat model of cerebral ischemia using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET. Method. Rats were divided into 5 groups: sham group, ischemia-reperfusion untreated (IRU group, DHI-1 group (DHI 1 mL/kg/d, DHI-2 group (DHI 2 mL/kg/d, and DHI-4 group (DHI 4 mL/kg/d. AII the treated groups were intraperitoneally injected with DHI daily for 14 days. The therapeutic effects in terms of cerebral infarct volume, neurological function, and cerebral glucose metabolism were evaluated. Expression of TNF-α and IL-1β was detected with enzyme-linked immunosorbent assay (ELISA. Levels of mature neuronal marker (NeuN, glial marker (GFAP, vascular density factor (vWF, and glucose transporter 1 (GLUT1 were assessed by immunohistochemistry. Results. Compared with the IRU group, rats treated with DHI showed dose dependent reductions in cerebral infarct volume and levels of proinflammatory cytokines, improvement of neurological function, and recovery of cerebral glucose metabolism. Meanwhile, the significantly increased numbers of neurons, gliocytes, and vessels and the recovery of glucose utilization were found in the peri-infarct region after DHI treatment using immunohistochemical analysis. Conclusion. This study demonstrated the metabolic recovery after DHI treatment by micro-PET imaging with 18F-FDG and the neuroprotective effects of DHI in a rat model of cerebral ischemic-reperfusion injury.

  6. Gypenoside attenuates renal ischemia/reperfusion injury in mice by inhibition of ERK signaling

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    YE, QIFA; ZHU, YI; YE, SHAOJUN; LIU, HONG; SHE, XINGGUO; NIU, YING; MING, YINGZI

    2016-01-01

    Gynostemma pentaphyllum is a traditional Chinese medicine reported to possess a wide range of health benefits. As the major component of G. pentaphyllum, gypenoside (GP) displays various anti-inflammatory and anti-oxidant properties. However, it is unclear whether GP can protect against ischemia/reperfusion (I/R)-induced renal injury, and the underlying molecular mechanisms associated with this process remain unknown. In the present study, a renal I/R injury model in C57BL/6 mice was established. It was observed that, following I/R, serum concentrations of creatinine (Cr) and blood urea nitrogen (BUN) were significantly increased (P<0.01), indicating renal injury. Pretreatment with GP (50 mg/kg) significantly inhibited I/R-induced upregulation of serum Cr and BUN (P<0.01). Furthermore, renal malondialdehyde levels were significantly reduced in the I/R+GP group, compared with the I/R group (P<0.01), whereas renal tissue superoxide dismutase activity was significantly higher in the I/R+GP group compared with the I/R group (P<0.01). Further investigation demonstrated that pretreatment with GP produced inhibitory effects on the I/R-induced production of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α and interferon-γ (P<0.01). In addition, heme oxygenase 1 (HO-1) expression levels were significantly increased in the I/R group compared with the control (P<0.01), indicating the presence of oxidative damage. However, the I/R-induced upregulation of HO-1 was significantly attenuated by pretreatment with GP (P<0.01), which also suppressed I/R-induced apoptosis by inhibiting pro-apoptotic Bax and upregulating anti-apoptotic Bcl-2 in renal cells (P<0.01). Finally, the activity of ERK signaling was significantly increased in the I/R+GP group compared with the I/R group (P<0.05), which may be associated with the protective effect of GP against I/R-induced renal cell apoptosis. To conclude, the present results suggest that GP produces

  7. Neutrophils accentuate renal cold ischemia-reperfusion injury. Dose-dependent protective effect of a platelet-activating factor receptor antagonist.

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    Riera, M; Torras, J; Herrero, I; Valles, J; Paubert-Braquet, M; Cruzado, J M; Alsina, J; Grinyo, J M

    1997-02-01

    This study was undertaken to evaluate whether the renal damage induced by cold ischemia-reperfusion was worsened by neutrophils (PMN), and if blockade of platelet-activating factor (PAF) could effectively decrease this injury. After flushing with EuroCollins, 85 kidneys from Sprague-Dawley rats underwent either no cold ischemia or a 4-h cold ischemia, and then were reperfused for 75 min at 37 degrees C and 100 mm Hg in an isolated perfusion circuit. Reperfusion was performed with a Krebs-Henseleit solution containing 4.5% albumin, with and without human PMN (7.5 x 10(5) cells/ml) and with and without addition of a PAF receptor antagonist (BN 52021). Hemodynamic and functional parameters were continuously assessed during reperfusion. At end of the study, PAF production was evaluated. Presence of PMN during reperfusion of nonischemic kidneys produced no alteration of functional parameters or PAF production. After 4-h cold ischemia, the presence of PMN during reperfusion produced a significant worsening of plasma flow rate, glomerular filtration rate and sodium reabsorption in comparison with kidneys reperfused without PMN. Also, higher production of PAF was observed in the kidneys reperfused with PMN than in the kidneys reperfused without PMN. After 4-h cold ischemia, addition of BN 52021 during reperfusion in the presence of PMN significantly increased the plasma flow rate, glomerular filtration rate and sodium reabsorption in comparison with kidneys reperfused without this PAF antagonist. This effect was dose dependent. After 4-h cold ischemia, addition of BN 52021 during reperfusion in the absence of PMN produced no significant effect on functional parameters in comparison with kidneys reperfused without this PAF antagonist. These results indicate that PMN contribute to renal cold ischemia-reperfusion injury evaluated in the isolated perfused kidney. Treatment with a PAF receptor antagonist attenuated this injury in a dose-dependent manner, which suggests that it

  8. THE EFFECT OF ISCHEMIC RE-PERFUSION INJURY PLUS PARTICLE INFUSION EMBOLISM ON THE APOPTOSIS OF RATS WITH PANCREATIC CANCER

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objectives. In an attempt to develop new method of treating the end- or mid-stage pancreatic cancer, we exam-ined the effect of isr hemie re-perfusion injury plus particle embolism on the pathology and cell apoptosis of pancreat-ic cancer in Spragiue Dawely rats.Methods. 9 rr g dimethylbeneanthracine (DMBA) were implanted directly into the parenchyma of pancreatictail of Sprague-Dawely rats. After establishment of tumor, the inferior splenic artery, a main supplying vessel topancreatic tail was subjected to blockade and re-opening for 30 min separately, then embolism particles were in-fused via the artery. Mterwards, artery was ligated. Pathological changes and cell apoptosis indicators (AI) ofpancreatic cancer were observed by light microscopy and ISEL respectively 14 days after the operation.Results. The prevalence of pancreatic cancer among DMBA-implanted rats evaluated 3 months to 4 months af-ter implantation was 59%. The volumes of the tumor in positive control group (B), pancreatic ischemic group(C), pancreatic ischemic re-perfusion injury group (D) were significantly larger than pancreatic ischemicre-perfusion injury plus particle thrombus group (E) (P < 0.01 ). The volumes of the tumor in groups D, E weresignificantly smalle than that in group C ( P < 0.01 ) . There was a significant difference in tumor size betweengroup B and group C ( P < 0. 01 ), but the difference was not significant between group D and group E ( P > 0.05 ).There was a signifieant infiltration of tumor tissue in group B rats, but strong inflammatory reaction was not noted.In groups C, D, E a localized tumor growth was observed; infiltration of inflammatory cells and proliferation offibroblasts and connective fiber were obvious, and some of these fibers grew into cancer nests and separate the tu-mor. The above findings were most conspicuous in group E. There was a significant difference in AI betweengroup E (13.7 ± 1.5) and other groups (P < 0. 01), with the difference being

  9. Protective effect of ischemic postconditioning on lung ischemia-reperfusion injury in rats and the role of heme oxygenase-1

    Institute of Scientific and Technical Information of China (English)

    XIA Zhong-yuan; GAO Jin; Ameer Kumar Ancharaz

    2009-01-01

    To investigate the effect of ischemic postconditioning (IPO) on acute lung ischemia-reperfusion (I/R) injury and the protein expression of haeme oxygenase-1 (H0-1), a cytoprotective defense against oxidative injury. Methods: After being anesthetized with chloralhy-drate, forty-eight healthy SD rats were randomly divided into 6 groups (8 in each): sham operation group (S group); I/R group: left lung hilum was clamped for 40 minutes followed by 105 minutes of reperfusion; IPO group: left lung hilum was clamped for40 minutes and postconditioned by 3 cycles of 30 seconds of reperfusion and 30 seconds of reocclusion; Hemin (HM)+ I/R group: hemin, an inducer of HO- 1 was injected intraperitoneally at 40 μmol.kg-1·day-1 for two con-secutive days prior to 40 minutes clamping of left lung hilum; ZnPPIX+IPO group: zinc protoporphyrin Ⅸ, an inhibitor of HO-1 was injected intraperitoneally at 20 mg·kg-1 24 hours prior to 40 minutes clamping of left lung hilum; and HM+S group: HM was administered as in the HM+I/R group without inducing lung I/R. Arterial partial pressure of oxygen (PaO2) and malondialdehyde (MDA) content in serum were assessed. The left lung was removed for determination of wet/dry lung weight ratio and expression of HO-1 protein by immuno-his-tochemical technique and for light microscopic examination. Results: The PaO2 was significantly lower in all the experimental groups compared with sham group (90 mm Hg ±11 mm Hg). However, the values ofPaO2 in IPO (81 mm Hg ±7 mm Hg) and HM+I/R (80 mm Hg±9 mm Hg) were higher than that in I/R (63 mm Hg±9 mm Hg) and ZnPPIX+IPO (65 mm Hg±8 mm Hg) groups (P<0.01). The protein expression of HO-1 in lung tissue was significantly increased in I/R group compared with S group (P<0.01). While the HO-1 protein expression was higher in IPO and HM+I/R groups as compared with I/R group (P<0.05, P<0.01). The lung wet/ dry (W/D) weight ratio and MDA content in serum were significantly increased in I/R group as compared with S

  10. Effects of Acupuncture Pretreatment on Ischemic Cardiac Muscle Cell Apoptosis and Gene Expression in Ischemia-reperfusion Rats

    Institute of Scientific and Technical Information of China (English)

    赵宇辉; 孙忠人; 崔学军

    2009-01-01

    目的:针灸预处理对缺血心肌具有保护作用.通过观察针刺预处理对心肌缺血再灌注损伤大鼠心肌细胞凋亡及HSP70mPNA表达的影响,探讨针刺预处理的心肌保护机制.方法:64只Wistar大鼠随机分为8组,即正常对照组,假手术组,缺血再灌注组,缺血预处理组,手捻针预处理日1次组,电针预处理日1次组,手捻针预处理日2次组,电针预处理日2次组.建立大鼠心肌缺血再灌注模型,采用原位杂交法测定心肌HSP70mRNA的表达,TUNEL法检测细胞凋亡.结果:与正常对照组、假手术组比较,缺血再灌注组细胞凋亡增加,HSP70 mRNA表达增加;与缺血再灌注组比较,针刺预处理使心肌细胞凋亡减少、HSP70mRNA表达增加,且针刺预处理日2次组作用强于针刺预处理日1次组和缺血预处理组.结论:针刺预处理能够抑制心肌缺血再灌注损伤大鼠心肌细胞凋亡,上调心肌HSP70mRNA的表达.针刺预处理每日2次的作用强于针剌预处理每日1次.%Objective:To investigate the protective effects of acupuncture pretreatment on ischemic myocardium,the protective mechanism of acupuncture pretreatment on ischemic myocardium was explored by observing the cardiac muscle cell apoptosis and the expression of HSP70 mRNA of ischemia-reperfusion injury rats treated with acupuncture pretreatment.Methods:Sixty-four Wistar rats were randomly divided into eight groups:control group,sham surgery group,ischemia-repertusion group,ischemia pretreatment group,manual acupuncture pretreatment group(once a day),electroacupuncture pretreatment group(once a day),manual acupuncture pretreatment group(twice a day),and electroacupuncture pretreatment group(twice a day).The reperfusion model of rat myocardial ischemia was made.Expression of HSP70 mRNA was assayed by in situ hyrbridization,and cell apoptosis by TUNEL.Results:Compared with those in the control group and the sham surgery group,the apoptosis and the expression of HSP70 m

  11. Protective and super-imposing effects of Estradiol , Breviscapini, Lumbrokinase In focal cerebral ischemic-reperfusion injury on rats

    Institute of Scientific and Technical Information of China (English)

    Shang huiFang; Luo ZuMing

    2000-01-01

    Baekgrouad: Postmenopausal estrogen replacement therapy is always associated with a decrease in risk of stroke incidence and mortality. The breviscapini and lumbrokinase can protect brain from ischemic injury..Experiments in animal models suggest estradiol can protect brain from ischemic injury. But we know little about the mechanism of brain protection role of estradiol. Espectically we don't know if estrodiol plus other brain protective drugs such as breviscapini and lumbrokinase have superimposing protection. Objective: To study protective function and its mechanism of estradio breviscapini and lumbrokinase after cerebral ischemic reperfusion tn overiectimiaed rat. Methods: We made the local ischemic repenfusion model with thread emgolism of right middle cerebral artery (MCA) of young female SD rars which werc bilaterally ovariectomized two weeks ago were used. These rats were randomized into sham-operated group, control group, estrodiol group, brevisacapini group, 10 SD rats each group. We admistrated each group with reseponsed treatment when rats were subjected to half an hour of MCAO. MCA were oecluded 2 hours and followed by 70 hours of reperfusion. Sham-poerated group were exposed cervical common artery and weren't occluded MCA. The rats were killed at 72 hours. The observed patameters each group listed: 1) The neurological deficit scores were made after MCAO 2 hours and bcforc killed. 2) Each group excluded sham operaated group were caculaled cerebral infarct volume ratio and edema volume with stereological microscoppe. 3) The level of Nitrc oxide (NO) in serum were determined with nitrate redutase method. 4) The level of Interlukin-I (IL-1) and tumor necrosis factot (TNF) were determined by biological activity method. 5) Ultrastructure of neuron were observed with electron microscope. All the rcsults from different groups were compared with each other. The drugs identified effictive in formcr study plus estradiot wcre admistratcd to rats to obscrvcd

  12. Risk factors of the renal dysfunction formation in patients with ischemic chronic heart failure

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    V. D. Syvolap

    2015-02-01

    Full Text Available The aim was to study prevalence of some risk factors of the renal dysfunction. Methods and results. 344 patients with ischemic chronic heart failure were included. Clinical, medical history, laboratory and instrumental data were analyzed. It was established that renal dysfunction is accompanied by traditional (age, hyperlipidemia, hypertension, myocardial infarction, obesity, left ventricular hypertrophy and non-traditional risk factors (hyperuricemia, atrial fibrillation, left ventricular ejection fraction, left atrial volume index, cystatin C whose role increases with a decrease in glomerular filtration rate. Conclusion. This shows the close relationship between traditional and non-traditional risk factors that contribute to the development of cardio-renal complications.

  13. Anticancer Drug 2-Methoxyestradiol Protects against Renal Ischemia/Reperfusion Injury by Reducing Inflammatory Cytokines Expression

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    Ying-Yin Chen

    2014-01-01

    Full Text Available Background. Ischemia/reperfusion (I/R injury is a major cause of acute renal failure and allograft dysfunction in kidney transplantation. ROS/inflammatory cytokines are involved in I/R injury. 2-Methoxyestradiol (2ME2, an endogenous metabolite of estradiol, inhibits inflammatory cytokine expression and is an antiangiogenic and antitumor agent. We investigated the inhibitory effect of 2ME2 on renal I/R injury and possible molecular actions. Methods. BALB/c mice were intraperitoneally injected with 2ME2 (10 or 20 mg/kg or vehicle 12 h before and immediately after renal I/R experiments. The kidney weight, renal function, tubular damages, and apoptotic response were examined 24 h after I/R injury. The expression of mRNA of interleukin-1β, tumor necrosis factor- (TNF α, caspase-3, hypoxia inducible factor- (HIF 1α, and proapoptotic Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3 in kidney tissue was determined using RT-PCR, while the expression of nuclear factor κB (NF-κB, BCL-2, and BCL-xL, activated caspase-9, and HIF-1α was determined using immunoblotting. In vitro, we determined the effect of 2ME2 on reactive oxygen species (ROS production and cell viability in antimycin-A-treated renal mesangial (RMC and tubular (NRK52E cells. Results. Serum creatinine and blood urea nitrogen were significantly higher in mice with renal I/R injury than in sham control and in I/R+2ME2-treated mice. Survival in I/R+2ME2-treated mice was higher than in I/R mice. Histological examination showed that 2ME2 attenuated tubular damage in I/R mice, which was associated with lower expression TNF-α, IL-1β, caspase-9, HIF-1α, and BNIP3 mRNA in kidney tissue. Western blotting showed that 2ME2 treatment substantially decreased the expression of activated caspase-9, NF-κB, and HIF-1α but increased the antiapoptotic proteins BCL-2 and BCL-xL in kidney of I/R injury. In vitro, 2MR2 decreased ROS production and increased cell viability in antimycin

  14. Nicotine protects kidney from renal ischemia/reperfusion injury through the cholinergic anti-inflammatory pathway.

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    Claude Sadis

    Full Text Available Kidney ischemia/reperfusion injury (I/R is characterized by renal dysfunction and tubular damages resulting from an early activation of innate immunity. Recently, nicotine administration has been shown to be a powerful inhibitor of a variety of innate immune responses, including LPS-induced toxaemia. This cholinergic anti-inflammatory pathway acts via the alpha7 nicotinic acetylcholine receptor (alpha7nAChR. Herein, we tested the potential protective effect of nicotine administration in a mouse model of renal I/R injury induced by bilateral clamping of kidney arteries. Renal function, tubular damages and inflammatory response were compared between control animals and mice receiving nicotine at the time of ischemia. Nicotine pretreatment protected mice from renal dysfunction in a dose-dependent manner and through the alpha7nAChR, as attested by the absence of protection in alpha7nAChR-deficient mice. Additionally, nicotine significantly reduced tubular damages, prevented neutrophil infiltration and decreased productions of the CXC-chemokine KC, TNF-alpha and the proinflammatory high-mobility group box 1 protein. Reduced tubular damage in nicotine pre-treated mice was associated with a decrease in tubular cell apoptosis and proliferative response as attested by the reduction of caspase-3 and Ki67 positive cells, respectively. All together, these data highlight that nicotine exerts a protective anti-inflammatory effect during kidney I/R through the cholinergic alpha7nAChR pathway. In addition, this could provide an opportunity to overcome the effect of surgical cholinergic denervation during kidney transplantation.

  15. Isoflurane anesthesia initiated at the onset of reperfusion attenuates oxidative and hypoxic-ischemic brain injury.

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    Sergey A Sosunov

    Full Text Available This study demonstrates that in mice subjected to hypoxia-ischemia (HI brain injury isoflurane anesthesia initiated upon reperfusion limits a release of mitochondrial oxidative radicals by inhibiting a recovery of complex-I dependent mitochondrial respiration. This significantly attenuates an oxidative stress and reduces the extent of HI brain injury. Neonatal mice were subjected to HI, and at the initiation of reperfusion were exposed to isoflurane with or without mechanical ventilation. At the end of HI and isoflurane exposure cerebral mitochondrial respiration, H2O2 emission rates were measured followed by an assessment of cerebral oxidative damage and infarct volumes. At 8 weeks after HI navigational memory and brain atrophy were assessed. In vitro, direct effect of isoflurane on mitochondrial H2O2 emission was compared to that of complex-I inhibitor, rotenone. Compared to controls, 15 minutes of isoflurane anesthesia inhibited recovery of the compex I-dependent mitochondrial respiration and decreased H2O2 production in mitochondria supported with succinate. This was associated with reduced oxidative brain injury, superior navigational memory and decreased cerebral atrophy compared to the vehicle-treated HI-mice. Extended isoflurane anesthesia was associated with sluggish recovery of cerebral blood flow (CBF and the neuroprotection was lost. However, when isoflurane anesthesia was supported with mechanical ventilation the CBF recovery improved, the event associated with further reduction of infarct volume compared to HI-mice exposed to isoflurane without respiratory support. Thus, in neonatal mice brief isoflurane anesthesia initiated at the onset of reperfusion limits mitochondrial release of oxidative radicals and attenuates an oxidative stress. This novel mechanism contributes to neuroprotective action of isoflurane. The use of mechanical ventilation during isoflurane anesthesia counterbalances negative effect of isoflurane anesthesia on

  16. Calpains and proteasomes mediate degradation of ryanodine receptors in a model of cardiac ischemic reperfusion.

    Science.gov (United States)

    Pedrozo, Zully; Sánchez, Gina; Torrealba, Natalia; Valenzuela, Rodrigo; Fernández, Carolina; Hidalgo, Cecilia; Lavandero, Sergio; Donoso, Paulina

    2010-03-01

    Type-2 ryanodine receptors (RyR2)--the calcium release channels of cardiac sarcoplasmic reticulum--have a central role in cardiac excitation-contraction coupling. In the heart, ischemia/reperfusion causes a rapid and significant decrease in RyR2 content but the mechanisms responsible for this effect are not fully understood. We have studied the involvement of three proteolytic systems--calpains, the proteasome and autophagy--on the degradation of RyR2 in rat neonatal cardiomyocyte cultures subjected to simulated ischemia/reperfusion (sI/R). We found that 8h of ischemia followed by 16h of reperfusion decreased RyR2 content by 50% without any changes in RyR2 mRNA. Specific inhibitors of calpains and the proteasome prevented the decrease of RyR2 caused by sI/R, implicating both pathways in its degradation. Proteasome inhibitors also prevented the degradation of calpastatin, the endogenous calpain inhibitor, hindering the activation of calpain induced by calpastatin degradation. Autophagy was activated during sI/R as evidenced by the increase in LC3-II and beclin-1, two proteins involved in autophagosome generation, and in the emergence of GFP-LC3 containing vacuoles in adenovirus GFP-LC3 transduced cardiomyocytes. Selective autophagy inhibition, however, induced even further RyR2 degradation, making unlikely the participation of autophagy in sI/R-induced RyR2 degradation. Our results suggest that calpain activation as a result of proteasome-induced degradation of calpastatin initiates RyR2 proteolysis, which is followed by proteasome-dependent degradation of the resulting RyR2 fragments. The decrease in RyR2 content during ischemia/reperfusion may be relevant to the decrease of heart contractility after ischemia.

  17. No evidence for activated autophagy in left ventricular myocardium at early reperfusion with protection by remote ischemic preconditioning in patients undergoing coronary artery bypass grafting.

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    Nilgün Gedik

    Full Text Available Remote ischemic preconditioning (RIPC by repeated brief limb ischemia/reperfusion reduces myocardial injury in patients undergoing coronary artery bypass grafting (CABG. Activation of signal transducer and activator of transcription 5 (STAT5 in left ventricular (LV myocardium at early reperfusion is associated with such protection. Autophagy, i.e., removal of dysfunctional cellular components through lysosomes, has been proposed as one mechanism of cardioprotection. Therefore, we analyzed whether or not the protection by RIPC is associated with activated autophagy.CABG patients were randomized to undergo RIPC (3×5 min blood pressure cuff inflation/5 min deflation or placebo (cuff deflated before skin incision (n = 10/10. Transmural myocardial biopsies were taken from the LV before cardioplegia (baseline and at early (5-10 min reperfusion. RIPC-induced protection was reflected by decreased serum troponin I concentration area under the curve (194±17 versus 709±129 ng/ml × 72 h, p = 0.002. Western blotting for beclin-1-phosphorylation and protein expression of autophagy-related gene 5-12 (ATG5-12 complex, light chain 3 (LC3, parkin, and p62 was performed. STAT3-, STAT5- and extracellular signal-regulated protein kinase 1/2 (ERK1/2-phosphorylation was used as positive control to confirm signal activation by ischemia/reperfusion.Signals of all analyzed autophagy proteins did not differ between baseline and early reperfusion and not between RIPC and placebo. STAT5-phosphorylation was greater at early reperfusion only with RIPC (2.2-fold, p = 0.02. STAT3- and ERK1/2-phosphorylation were greater at early reperfusion with placebo and RIPC (≥2.7-fold versus baseline, p≤0.05.Protection through RIPC in patients undergoing CABG surgery does not appear to be associated with enhanced autophagy in LV myocardium at early reperfusion.

  18. Effects of alprostadil and iloprost on renal, lung, and skeletal muscle injury following hindlimb ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Erer, Dilek; Özer, Abdullah; Demirtaş, Hüseyin; Gönül, İpek Işık; Kara, Halil; Arpacı, Hande; Çomu, Faruk Metin; Oktar, Gürsel Levent; Arslan, Mustafa; Küçük, Ayşegül

    2016-01-01

    To evaluate the effects of alprostadil (prostaglandin [PGE1] analog) and iloprost (prostacyclin [PGI2] analog) on renal, lung, and skeletal muscle tissues after ischemia reperfusion (I/R) injury in an experimental rat model. Wistar albino rats underwent 2 hours of ischemia via infrarenal aorta clamping with subsequent 2 hours of reperfusion. Alprostadil and iloprost were given starting simultaneously with the reperfusion period. Effects of agents on renal, lung, and skeletal muscle (gastrocnemius) tissue specimens were examined. Renal medullary congestion, cytoplasmic swelling, and mean tubular dilatation scores were significantly lower in the alprostadil-treated group than those found in the I/R-only group (Piloprost-treated groups (P=0.017 and P=0.001; Piloprost-treated group than the scores found in the nontreated I/R group (Piloprost significantly reduce lung tissue I/R injury. Alprostadil has more prominent protective effects against renal I/R injury, while iloprost is superior in terms of protecting the skeletal muscle tissue against I/R injury.

  19. Protective Effect of CXCR3+CD4+CD25+Foxp3+ Regulatory T Cells in Renal Ischemia-Reperfusion Injury

    Science.gov (United States)

    Jun, Cao; Qingshu, Li; Ke, Wei; Ping, Li; Jun, Dong; Jie, Luo; Su, Min

    2015-01-01

    Regulatory T cells (Tregs) suppress excessive immune responses and are potential therapeutic targets in autoimmune disease and organ transplantation rejection. However, their role in renal ischemia-reperfusion injury (IRI) is unclear. Levels of Tregs and expression of CXCR3 in Tregs were analyzed to investigate their function in the early phase of renal IRI. Mice were randomly divided into Sham, IRI, and anti-CD25 (PC61) + IRI groups. The PC61 + IRI group was established by i.p. injection of PC61 monoclonal antibody (mAb) to deplete Tregs before renal ischemia. CD4+CD25+Foxp3+ Tregs and CXCR3 on Tregs were analyzed by flow cytometry. Blood urea nitrogen (BUN), serum creatinine (Scr) levels, and tubular necrosis scores, all measures of kidney injury, were greater in the IRI group than in the Sham group. Numbers of Tregs were increased at 72 h after reperfusion in kidney. PC61 mAb preconditioning decreased the numbers of Tregs and aggravated kidney injury. There was no expression of CXCR3 on Tregs in normal kidney, while it expanded at 72 h after reperfusion and inversely correlated with BUN, Scr, and kidney histology score. This indicated that recruitment of Tregs into the kidney was related to the recovery of renal function after IRI and CXCR3 might be involved in the migration of Tregs. PMID:26273136

  20. Protective Effect of CXCR3+CD4+CD25+Foxp3+ Regulatory T Cells in Renal Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Cao Jun

    2015-01-01

    Full Text Available Regulatory T cells (Tregs suppress excessive immune responses and are potential therapeutic targets in autoimmune disease and organ transplantation rejection. However, their role in renal ischemia-reperfusion injury (IRI is unclear. Levels of Tregs and expression of CXCR3 in Tregs were analyzed to investigate their function in the early phase of renal IRI. Mice were randomly divided into Sham, IRI, and anti-CD25 (PC61 + IRI groups. The PC61 + IRI group was established by i.p. injection of PC61 monoclonal antibody (mAb to deplete Tregs before renal ischemia. CD4+CD25+Foxp3+ Tregs and CXCR3 on Tregs were analyzed by flow cytometry. Blood urea nitrogen (BUN, serum creatinine (Scr levels, and tubular necrosis scores, all measures of kidney injury, were greater in the IRI group than in the Sham group. Numbers of Tregs were increased at 72 h after reperfusion in kidney. PC61 mAb preconditioning decreased the numbers of Tregs and aggravated kidney injury. There was no expression of CXCR3 on Tregs in normal kidney, while it expanded at 72 h after reperfusion and inversely correlated with BUN, Scr, and kidney histology score. This indicated that recruitment of Tregs into the kidney was related to the recovery of renal function after IRI and CXCR3 might be involved in the migration of Tregs.

  1. Effects of alprostadil and iloprost on renal, lung, and skeletal muscle injury following hindlimb ischemia–reperfusion injury in rats

    Science.gov (United States)

    Erer, Dilek; Özer, Abdullah; Demirtaş, Hüseyin; Gönül, İpek Işık; Kara, Halil; Arpacı, Hande; Çomu, Faruk Metin; Oktar, Gürsel Levent; Arslan, Mustafa; Küçük, Ayşegül

    2016-01-01

    Objectives To evaluate the effects of alprostadil (prostaglandin [PGE1] analog) and iloprost (prostacyclin [PGI2] analog) on renal, lung, and skeletal muscle tissues after ischemia reperfusion (I/R) injury in an experimental rat model. Materials and methods Wistar albino rats underwent 2 hours of ischemia via infrarenal aorta clamping with subsequent 2 hours of reperfusion. Alprostadil and iloprost were given starting simultaneously with the reperfusion period. Effects of agents on renal, lung, and skeletal muscle (gastrocnemius) tissue specimens were examined. Results Renal medullary congestion, cytoplasmic swelling, and mean tubular dilatation scores were significantly lower in the alprostadil-treated group than those found in the I/R-only group (Palprostadil- and iloprost-treated groups (P=0.017 and P=0.001; PAlprostadil and iloprost significantly reduce lung tissue I/R injury. Alprostadil has more prominent protective effects against renal I/R injury, while iloprost is superior in terms of protecting the skeletal muscle tissue against I/R injury. PMID:27601882

  2. Protective and super-imposing effects of Estradiol , Breviscapini, Lumbrokinase In focal cerebral ischemic-reperfusion injury on rats

    Institute of Scientific and Technical Information of China (English)

    Shang huiFang; Luo ZuMing

    2000-01-01

    Baekgrouad: Postmenopausal estrogen replacement therapy is always associated with a decrease in risk of stroke incidence and mortality. The breviscapini and lumbrokinase can protect brain from ischemic injury..Experiments in animal models suggest estradiol can protect brain from ischemic injury. But we know little about the mechanism of brain protection role of estradiol. Espectically we don't know if estrodiol plus other brain protective drugs such as breviscapini and lumbrokinase have superimposing protection. Objective: To study protective function and its mechanism of estradio breviscapini and lumbrokinase after cerebral ischemic reperfusion tn overiectimiaed rat. Methods: We made the local ischemic repenfusion model with thread emgolism of right middle cerebral artery (MCA) of young female SD rars which werc bilaterally ovariectomized two weeks ago were used. These rats were randomized into sham-operated group, control group, estrodiol group, brevisacapini group, 10 SD rats each group. We admistrated each group with reseponsed treatment when rats were subjected to half an hour of MCAO. MCA were oecluded 2 hours and followed by 70 hours of reperfusion. Sham-poerated group were exposed cervical common artery and weren't occluded MCA. The rats were killed at 72 hours. The observed patameters each group listed: 1) The neurological deficit scores were made after MCAO 2 hours and bcforc killed. 2) Each group excluded sham operaated group were caculaled cerebral infarct volume ratio and edema volume with stereological microscoppe. 3) The level of Nitrc oxide (NO) in serum were determined with nitrate redutase method. 4) The level of Interlukin-I (IL-1) and tumor necrosis factot (TNF) were determined by biological activity method. 5) Ultrastructure of neuron were observed with electron microscope. All the rcsults from different groups were compared with each other. The drugs identified effictive in formcr study plus estradiot wcre admistratcd to rats to obscrvcd

  3. Erdosteine improves oxidative damage in a rat model of renal ischemia-reperfusion injury.

    Science.gov (United States)

    Gurel, A; Armutcu, F; Cihan, A; Numanoglu, K V; Unalacak, M

    2004-01-01

    The aim of the present study was to determine the effects of erdosteine, a new antioxidant and anti-inflammatory agent, on lipid peroxidation, neutrophil infiltration, and antioxidant enzyme activities in a rat model of renal ischemia-reperfusion (I/R) injury. Twenty-eight rats were divided into three groups: sham operation, I/R, and I/R plus erdosteine groups. After the experimental procedure, rats were sacrificed and kidneys were removed and prepared for malondialdehyde (MDA) levels, myeloperoxidase (MPO), xanthine oxidase (XO), catalase (CAT) and superoxide dismutase (SOD) activities. MDA level, MPO and XO activities were significantly increased in the I/R group. On the other hand, SOD and CAT activities were found to be decreased in the I/R group compared to the sham group. Pretreatment with erdosteine significantly diminished tissue MDA level, MPO and XO activities. Our data support a role for erdosteine in attenuation in renal damage after I/R injury of the kidney, in part at least by inhibition of neutrophil sequestration and XO activity.

  4. Low molecular weight fucoidan against renal ischemia-reperfusion injury via inhibition of the MAPK signaling pathway.

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    Jihui Chen

    Full Text Available BACKGROUND: Ischemia reperfusion injury (IRI is a leading cause of acute kidney injury (AKI in both native and transplanted kidneys. The objective of the present study was to evaluate whether low-molecular-weight fucoidan (LMWF could attenuate renal IRI in an animal model and in vitro cell models and study the mechanisms in which LMWF protected from IRI. METHODOLOGY/PRINCIPAL FINDINGS: Male mice were subjected to right renal ischemia for 30 min and reperfusion for 24 h, or to a sham operation with left kidney removed. Kidneys undergone IR showed characteristic morphological changes, such as tubular dilatation, and brush border loss. However, LMWF significantly corrected the renal dysfunction and the abnormal levels of MPO, MDA and SOD induced by IR. LMWF also inhibited the activation of MAPK pathways, which consequently resulted in a significant decrease in the release of cytochrome c from mitochondria, ratios of Bax/Bcl-2 and cleaved caspase-3/caspase-3, and phosphorylation of p53. LMWF alleviated hypoxia-reoxygenation or CoCl(2 induced cell viability loss and ΔΨm dissipation in HK2 renal tubular epithelial cells, which indicates LMWF may result in an inhibition of the apoptosis pathway through reducing activity of MAPK pathways in a dose-dependent manner. CONCLUSIONS/SIGNIFICANCE: Our in vivo and in vitro studies show that LMWF ameliorates acute renal IRI via inhibiting MAPK signaling pathways. The data provide evidence that LMWF may serve as a potential therapeutic agent for acute renal IRI.

  5. Protein oxidation and lipid peroxidation after renal ischemia-reperfusion injury: protective effects of erdosteine and N-acetylcysteine.

    Science.gov (United States)

    Erdogan, Hasan; Fadillioglu, Ersin; Yagmurca, Murat; Uçar, Muharrem; Irmak, M Kemal

    2006-02-01

    Oxygen radicals have roles in the renal ischemia-reperfusion (IR) injury usually encountered in several conditions such as renal transplantation. The aim of this study was to investigate the effects of erdosteine and N-acetylcysteine (NAC) on the oxidant/antioxidant status and microscopy of renal tissues after IR injury. Male Sprague-Dawley rats were randomly assigned to four groups: control untreated rats, IR (30 min ischemia and 120 min reperfusion), IR + NAC (i.p.; 180 mg/kg) and IR + erdosteine (oral; 50 mg/kg/day for 2 days before experiments) groups. After unilateral renal IR, the right kidney was rapidly excised and sectioned vertically into two pieces for microscopic examination and biochemical analysis. Erdosteine and NAC treatment did not cause any significant change in the activity of superoxide dismutase (SOD) in comparison with the IR group, even if the SOD activity increased in IR groups than in the control group. Catalase (CAT) activity was decreased in the IR group in comparison with control and IR + erdosteine groups (Perdosteine group than in the IR + NAC group (PErdosteine or NAC treatments ameliorated these increased TBARS and PC contents in comparison with the IR group (PErdosteine but not NAC apparently reduced the renal tissue damage. The pathological damage score after IR was significantly reduced after erdosteine treatment (PErdosteine and NAC treatments improved the biochemical results of IR injury. However, on microscopic evaluations, animals receiving erdosteine showed a great reduction in renal damage when compared with the NAC group.

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

    Science.gov (United States)

    Ling, Haibin; Chen, Hongguang; Wei, Miao; Meng, Xiaoyin; Yu, Yonghao; Xie, Keliang

    2016-02-01

    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.

  7. Time to Reperfusion and Treatment Effect for Acute Ischemic Stroke : A Randomized Clinical Trial

    NARCIS (Netherlands)

    Fransen, Puck S S; Berkhemer, Olvert A; Lingsma, Hester F; Beumer, Debbie; van den Berg, Lucie A; Yoo, Albert J; Schonewille, Wouter J; Vos, Jan Albert; Nederkoorn, Paul J; Wermer, Marieke J H; van Walderveen, Marianne A A; Staals, Julie; Hofmeijer, Jeannette; van Oostayen, Jacques A; Lycklama À Nijeholt, Geert J; Boiten, Jelis; Brouwer, Patrick A; Emmer, Bart J; de Bruijn, Sebastiaan F; van Dijk, Lukas C; Kappelle, L Jaap; Lo, Rob H; van Dijk, Ewoud J; de Vries, Joost; de Kort, Paul L M; van den Berg, J S Peter; van Hasselt, Boudewijn A A M; Aerden, Leo A M; Dallinga, René J; Visser, Marieke C; Bot, Joseph C J; Vroomen, Patrick C; Eshghi, Omid; Schreuder, Tobien H C M L; Heijboer, Roel J J; Keizer, Koos; Tielbeek, Alexander V; den Hertog, Heleen M; Gerrits, Dick G; van den Berg-Vos, Renske M; Karas, Giorgos B; Steyerberg, Ewout W; Flach, H Zwenneke; Marquering, Henk A; Sprengers, Marieke E S; Jenniskens, Sjoerd F M; Beenen, Ludo F M; van den Berg, René; Koudstaal, Peter J; van Zwam, Wim H; Roos, Yvo B W E M; van Oostenbrugge, Robert J; Majoie, Charles B L M; van der Lugt, Aad; Dippel, Diederik W J

    2016-01-01

    Importance: Intra-arterial treatment (IAT) for acute ischemic stroke caused by intracranial arterial occlusion leads to improved functional outcome in patients treated within 6 hours after onset. The influence of treatment delay on treatment effect is not yet known. Objective: To evaluate the influe

  8. Time to Reperfusion and Treatment Effect for Acute Ischemic Stroke : A Randomized Clinical Trial

    NARCIS (Netherlands)

    Fransen, Puck S S; Berkhemer, Olvert A; Lingsma, Hester F; Beumer, Debbie; van den Berg, Lucie A; Yoo, Albert J; Schonewille, Wouter J; Vos, Jan Albert; Nederkoorn, Paul J; Wermer, Marieke J H; van Walderveen, Marianne A A; Staals, Julie; Hofmeijer, Jeannette; van Oostayen, Jacques A; Lycklama À Nijeholt, Geert J; Boiten, Jelis; Brouwer, Patrick A; Emmer, Bart J; de Bruijn, Sebastiaan F; van Dijk, Lukas C; Kappelle, L Jaap; Lo, Rob H; van Dijk, Ewoud J; de Vries, Joost; de Kort, Paul L M; van den Berg, J S Peter; van Hasselt, Boudewijn A A M; Aerden, Leo A M; Dallinga, René J; Visser, Marieke C; Bot, Joseph C J; Vroomen, Patrick C; Eshghi, Omid; Schreuder, Tobien H C M L; Heijboer, Roel J J; Keizer, Koos; Tielbeek, Alexander V; den Hertog, Heleen M; Gerrits, Dick G; van den Berg-Vos, Renske M; Karas, Giorgos B; Steyerberg, Ewout W; Flach, H Zwenneke; Marquering, Henk A; Sprengers, Marieke E S; Jenniskens, Sjoerd F M; Beenen, Ludo F M; van den Berg, René; Koudstaal, Peter J; van Zwam, Wim H; Roos, Yvo B W E M; van Oostenbrugge, Robert J; Majoie, Charles B L M; van der Lugt, Aad; Dippel, Diederik W J

    2016-01-01

    IMPORTANCE: Intra-arterial treatment (IAT) for acute ischemic stroke caused by intracranial arterial occlusion leads to improved functional outcome in patients treated within 6 hours after onset. The influence of treatment delay on treatment effect is not yet known. OBJECTIVE: To evaluate the influe

  9. Remote ischemic conditioning enhanced the early recovery of renal function in recipients after kidney transplantation: a randomized controlled trial.

    Science.gov (United States)

    Wu, Jianyong; Feng, Xiaoxiao; Huang, Hongfeng; Shou, Zhangfei; Zhang, Xiaohui; Wang, Rending; Chen, Yanyan; Chen, Jianghua

    2014-05-01

    To investigate whether remote ischemic conditioning (RIC) can attenuate ischemic reperfusion injury (IRI) in recipients after kidney transplantation using donation after cardiac death. Forty-eight recipients referred for kidney transplantation were recruited. The paired recipients who received the kidneys from the same donor were randomly assigned (one received RIC and the other did not). RIC was induced by three 5-min cycles of brief repetitive ischemia and reperfusion by clamping the exposed external iliac artery. Blood samples were withdrawn at hour 2, hour 12, days 1-7, day 14, and day 30 to measure serum creatinine level and estimated glomerular filtration rate after transplantation. Urine samples were collected at hours 2, 12, 24, and 48 to measure urine neutrophil gelatinase-associated lipocalin after transplantation. Renal tissues were obtained at 30 min for histologic changes after transplantation. There were no significant differences in clinical characteristics of the recipients and donors between RIC and control groups. The serum creatinine level was lower in the RIC group compared with that of the control group (12 h, days 1-14, P  0.05); the estimated glomerular filtration rate was higher in the RIC group compared with that of the control group (12 h, days 1-14, P 0.05); urine neutrophil gelatinase-associated lipocalin, an early marker of IRI, was lower in the RIC group at hours 2, 12, 24, and 48 (2 h, 48 h, P > 0.05; 12 h, 24 h, P control group. The graft pathology showed no differences between RIC and control groups. RIC enhanced the early recovery of renal function in recipients after kidney transplantation. Our results provide a novel potential approach to attenuate transplantation-associated IRI. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Protective effect of everolimus on renal ischemia reperfusion injury in rats

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    Tamer Sagiroglu

    2014-01-01

    Full Text Available The aim of this study was to determine the effect of everolimus and tacrolimus pretreatments on renal morphology and function in a rat ischemia reperfusion (I/R model. Twenty-eight male Sprague-Dawley rats were randomly assigned to saline + sham operation, saline + I/R (IR, tacrolimus + I/R (TRL + I/R and everolimus + I/R (ERL + I/R groups. Saline and active treatments were administered intraperitoneally for seven consecutive days before the surgery. The suprarenal aorta was clamped to achieve warm ischemia, except in the sham group. Right nephrectomy was performed in all animals and histology was examined. Renal function was assessed on post-operative Day 7 by Tc-99m dimercaptosuccinic acid (DMSA scintigraphy, glomerular filtration rate (GFR and serum biochemistry. Both everolimus and tacrolimus preserved serum creatinine and blood urea nitrogen levels, but only everolimus preserved GFR (0.74 ± 0.36, 1.20 ± 0.37 and 2.24 ± 0.32 mL/min for I/R, TRL + I/R and ERL + I/R, respectively, P < 0.001. %ID values for sham, I/R, TRL + I/R and ERL + I/R were 55 ± 3, 47 ± 4, 45 ± 6 and 62 ± 7 (P < 0.001. On histologic evaluation, ERL + I/R showed less tubular damage and necrosis than I/R, as well as TRL + I/R. Within the confines of this rat warm ischemia model, everolimus pre-treatment was useful in preserving renal function following I/R injury. The possibility of using everolimus as a pre-conditioning agent for I/R injury in kidney transplantation should be further explored.

  11. The role of ischemic preconditioning at the gracilis muscle of rats in the early phase of reperfusion injury

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    Webster Ronaldo Scholze

    2006-01-01

    Full Text Available PURPOSE: Verify the role of ischemic preconditioning (IPC in ischemia and reperfusion injury on gracilis muscle of rats. METHODS: Wistar rats (n=30 were distributed in three groups, I/R and IPC groups were subdivided concerning ischemia time. A near-amputation model of the posterior limb was produced by a hip joint level incision, preserving the vascular bundle and the femur bone and ischemia was induced for 2h and 4h, G-I 2h/R (n=6 and G-I 4h/R (n=6, followed by 1h of vascular reperfusion. The preconditioned groups, G-PCI 2h (n=6 and G-PCI 4h (n=6, were preceded by 3 cycles of 5min of ischemia followed by 5min of vascular reperfusion before sustained ischemia. In the Control Group, C-G (n=6 animals were subjected to regional approach. The analysis was done with Light Microscopy (LM. RESULTS: The levels of fibril fragmentation were progressive in the G-I 2h/R (67% of muscle preservation and in the G-I4 h/R (0% of muscle preservation. However in the group of the precondition the lesion degree being in level similar to the group controls in the G-I 2h/R (100% of muscle preservation while at G-I 4h/r occur less protection (67% of muscle preservation. The degree of tissue inflammatory reaction was worst at G-I 4h/R (0% without inflammation signals than at G-I 2h/R (50% without inflammation signals; while in the precondition group G-IPC-2h (83% without inflammation signals was better than the G-IPC-4h (67% without inflammation signals. The vascular stasis was absent only in 17% of the G-I 4h/R and in 33% of the G-I 2h/R. In precondition group, however, the vascular stasis was absent in 33% at G-IPC 2h and absent in 50% at G-IPC 4h. CONCLUSION: The IPC showed, in an earlier phase, a benefic role at I/R derived injury on gracilis muscle of rats, as proven for the largest preservation of the fibers muscular, smaller inflammatory reaction and smaller vascular stasis.

  12. Prognostic Relationships between Microbleed, Lacunar Infarction, White Matter Lesion, and Renal Dysfunction in Acute Ischemic Stroke Survivors.

    Science.gov (United States)

    Jeon, Jae Woong; Jeong, Hye Seon; Choi, Dae Eun; Ham, Young Rok; Na, Ki Ryang; Lee, Kang Wook; Shin, Jong Wook; Kim, Jei

    2017-02-01

    It is well known that renal dysfunction and cerebral small-vessel disease (SVD), including microbleed, lacunar infarction, and white matter lesion (WML), are associated with poor prognosis after ischemic stroke. However, the prognostic relationship between renal dysfunction and SVD has not been well evaluated in acute ischemic stroke survivors. Therefore, in this study, we evaluated the prognostic relationships between estimated glomerular filtration rate (eGFR) and cerebral SVD after acute ischemic stroke. We retrospectively reviewed the clinical and radiological data of acute ischemic stroke survivors with decreased eGFR (acute ischemic stroke survivors. Both renal impairment and the presence of SVD were predictors of poor poststroke survival. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  13. Sesamin protects against renal ischemia reperfusion injury by promoting CD39-adenosine-A2AR signal pathway in mice.

    Science.gov (United States)

    Li, Ke; Gong, Xia; Kuang, Ge; Jiang, Rong; Wan, Jingyuan; Wang, Bin

    2016-01-01

    Ischemia reperfusion injury (IRI) is a leading cause of acute kidney injury with high morbidity and mortality due to limited therapy. Here, we examine whether sesamin attenuates renal IRI in an animal model and explore the underlying mechanisms. Male mice were subjected to right renal ischemia for 30 min followed by reperfusion for 24 h with sesamin (100 mg/kg) during which the left kidney was removed. Renal damage and function were assessed subsequently. The results showed that sesamin reduced kidney ischemia reperfusion injury, as assessed by decreased serum creatinine (Scr) and Blood urea nitrogen (BUN), alleviated tubular damage and apoptosis. In addition, sesamin inhibited neutrophils infiltration and pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β production in IR-preformed kidney. Notably, sesamin promoted the expression of CD39, A2A adenosine receptor (A2AAR), and A2BAR mRNA and protein as well as adenosine production. Furthermore, CD39 inhibitor or A2AR antagonist abolished partly the protection of sesamin in kidney IRI. In conclusion, sesamin could effectively protect kidney from IRI by inhibiting inflammatory responses, which might be associated with promoting the adenosine-CD39-A2AR signaling pathway.

  14. Role of P-selectin and anti-P-selectin monoclonal antibody in apoptosis during hepatic/renal ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Pei Wu; Xiao Li; Tong Zhou; Wei Ming Wang; Nan Chen; De Chang Dong; Ming Jun Zhang; Jin Lian Chen

    2000-01-01

    AIM To evaluale the potential role of P-selectin and anti-P-selectin monoclonal antibody (mAb) in apoptosis during hepatic/renal ischemiareperfusion injury. METHODS Plasma P-selectin level, hepatic/renal P-selectin expression and cell apoptosis were detected in rat model of hepatic/ renal ischemia-reperfusion injury. ELISA, immunohistochemistry and TUNEL were used. Some ischemia-reperfusion rats were treated with antiP-selectin mAb. RESULTS Hepatic/ renal function insufficiency, up-regulated expression of P-selectin in plasma and hepatic/renal tissue, hepatic/renal histopathological damages and cell apoptosis were found in rats with hepatic/renal ischemiareperfusion injury, while these changes became less conspicuous in animals treated with anti-P selectin mAb. CONCLUSION P-selectin might mediate neutrophil infiltration and cell apoptosis and contribute to hepatic/renal ischemia-reperfusion injury, anti-P-selectin mAb might be an efficient approach for the prevention and treatment of hepatic/renal ischemia-reperfusion injury.

  15. Noninvasive Ventilatory Correction as an Adjunct to an Experimental Systemic Reperfusion Therapy in Acute Ischemic Stroke

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    Kristian Barlinn

    2010-01-01

    Full Text Available Background. Obstructive sleep apnea (OSA is a common condition in patients with acute ischemic stroke and associated with early clinical deterioration and poor functional outcome. However, noninvasive ventilatory correction is hardly considered as a complementary treatment option during the treatment phase of acute ischemic stroke. Summary of Case. A 55-year-old woman with an acute middle cerebral artery (MCA occlusion received intravenous tissue plasminogen activator (tPA and enrolled into a thrombolytic research study. During tPA infusion, she became drowsy, developed apnea episodes, desaturated and neurologically deteriorated without recanalization, re-occlusion or intracerebral hemorrhage. Urgent noninvasive ventilatory correction with biphasic positive airway pressure (BiPAP reversed neurological fluctuation. Her MCA completely recanalized 24 hours later. Conclusions. Noninvasive ventilatory correction should be considered more aggressively as a complementary treatment option in selected acute stroke patients. Early initiation of BiPAP can stabilize cerebral hemodynamics and may unmask the true potential of other therapies.

  16. Knockout of Toll-Like Receptors 2 and 4 Prevents Renal Ischemia-Reperfusion-Induced Cardiac Hypertrophy in Mice.

    Science.gov (United States)

    Trentin-Sonoda, Mayra; da Silva, Rogério Cirino; Kmit, Fernanda Vieira; Abrahão, Mariana Vieira; Monnerat Cahli, Gustavo; Brasil, Guilherme Visconde; Muzi-Filho, Humberto; Silva, Paulo André; Tovar-Moll, Fernanda Freire; Vieyra, Adalberto; Medei, Emiliano; Carneiro-Ramos, Marcela Sorelli

    2015-01-01

    We investigated whether the pathways linked to Toll-like receptors 2 and 4 (TLRs) are involved in renal ischemia-reperfusion (I/R)-induced cardiac hypertrophy. Wild type (WT) C57BL/6J, TLR2-/- and TLR4-/- mice were subjected to left kidney ischemia for 60 min followed by reperfusion for 5, 8, 12 and 15 days. Proton density magnetic resonance showed alterations in the injured kidney from WT mice, together with signs of parenchymal edema and higher levels of vimentin mRNA, accompanied by: (i) small, but significant, increase in serum urea after 24 h, (ii) 100% increase in serum creatinine at 24 h. A serum peak of inflammatory cytokines occurred after 5 days of reperfusion. Heart weight/body weight and heart weight/tibia length ratios increased after 12 and 15 days of reperfusion, respectively. Cardiac hypertrophy markers, B-type natriuretic peptide (BNP) and α-actin, left ventricle mass, cardiac wall thickness and myocyte width increased after 15 days of reperfusion, together with longer QTc and action potential duration. Cardiac TLRs, MyD88, HSP60 and HSP70 mRNA levels also increased. After 15 days of reperfusion, absence of TLRs prevented cardiac hypertrophy, as reflected by similar values of left ventricular cardiac mass and heart weight/body weight ratio compared to the transgenic Sham. Renal tissular injury also ameliorated in both knockout mice, as revealed by the comparison of their vimentin mRNA levels with those found in the WT on the same day after I/R. The I/R TLR2-/- group had TNF-α, IFN-γ and IL-1β levels similar to the non-I/R group, whereas the TLR4-/- group conserved the p-NF-κB/NF- κB ratio contrasting with that found in TLR2-/-. We conclude: (i) TLRs are involved in renal I/R-induced cardiac hypertrophy; (ii) absence of TLRs prevents I/R-induced cardiac hypertrophy, despite renal lesions seeming to evolve towards those of chronic disease; (iii) TLR2 and TLR4 selectively regulate the systemic inflammatory profile and NF- κB activation.

  17. Rosiglitazone Affects Nitric Oxide Synthases and Improves Renal Outcome in a Rat Model of Severe Ischemia/Reperfusion Injury

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    Boris Betz

    2012-01-01

    Full Text Available Background. Nitric oxide (NO-signal transduction plays an important role in renal ischemia/reperfusion (I/R injury. NO produced by endothelial NO-synthase (eNOS has protective functions whereas NO from inducible NO-synthase (iNOS induces impairment. Rosiglitazone (RGZ, a peroxisome proliferator-activated receptor (PPAR-γ agonist exerted beneficial effects after renal I/R injury, so we investigated whether this might be causally linked with NOS imbalance. Methods. RGZ (5 mg/kg was administered i.p. to SD-rats (f subjected to bilateral renal ischemia (60 min. Following 24 h of reperfusion, inulin- and PAH-clearance as well as PAH-net secretion were determined. Morphological alterations were graded by histopathological scoring. Plasma NOx-production was measured. eNOS and iNOS expression was analyzed by qPCR. Cleaved caspase 3 (CC3 was determined as an apoptosis indicator and ED1 as a marker of macrophage infiltration in renal tissue. Results. RGZ improves renal function after renal I/R injury (PAH-/inulin-clearance, PAH-net secretion and reduces histomorphological injury. Additionally, RGZ reduces NOx plasma levels, ED-1 positive cell infiltration and CC3 expression. iNOS-mRNA is reduced whereas eNOS-mRNA is increased by RGZ. Conclusion. RGZ has protective properties after severe renal I/R injury. Alterations of the NO pathway regarding eNOS and iNOS could be an explanation of the underlying mechanism of RGZ protection in renal I/R injury.

  18. Neuroprotection of GST, an extract of traditional Chinese herb, against ischemic brain injury induced by transient brain ischemia and reperfusion in rat hippocampus.

    Science.gov (United States)

    Sun, Ya-Feng; Pei, Dong-Sheng; Zhang, Qing-Xiu; Zhang, Guang-Yi

    2008-06-01

    In this study, we investigated the effect of GST, an extract of Chinese traditional herb, on transient brain ischemia/reperfusion-induced neuronal cell death. Immunoblotting was used to detect the phosphorylation of MLK, JNK and c-jun. Transient (15 minutes) brain ischemia was induced by the four-vessel occlusion in Sprague-Dawley rats. GST was administrated to the SD rats 20 minutes before ischemia or 1 hour after ischemia. Our data showed that the pretreatment of GST could inhibit phosphorylation of MLK, JNK and c-jun. Moreover, GST showed potent neuroprotective effects on ischemic brain damage in vivo and administration of it 1 hour after ischemia also achieved the protective effects. These results indicate that GST has a prominent neuroprotection action against brain ischemic damage and provides a promising therapeutic approach for ischemic brain injury.

  19. Ischemic post-conditioning attenuates acute lung injury induced by intestinal ischemia-reperfusion in mice: role of Nrf2.

    Science.gov (United States)

    Meng, Qing-Tao; Cao, Chen; Wu, Yang; Liu, Hui-Min; Li, Wei; Sun, Qian; Chen, Rong; Xiao, Yong-Guang; Tang, Ling-Hua; Jiang, Ying; Leng, Yan; Lei, Shao-Qing; Lee, Chris C; Barry, Devin M; Chen, Xiangdong; Xia, Zhong-Yuan

    2016-10-01

    Intestinal ischemic post-conditioning (IPo) protects against lung injury induced by intestinal ischemia-reperfusion (IIR) partly through promotion of expression and function of heme oxygenase-1 (HO-1). NF-E2-related factor-2 (Nrf2) is a key transcription factor that interacts with HO-1 and regulates antioxidant defense. However, the role of Nrf2 in IPo protection of IIR-induced pulmonary injury is not completely understood. Here we show that IPo significantly attenuated IIR-induced lung injury and suppressed oxidative stress and systemic inflammatory responses. IPo also increased the expression of both Nrf2 and HO-1. Consistently, the beneficial effects of IPo were abolished by ATRA and Brusatol, potent inhibitors of Nrf2. Moreover, the Nrf2 agonist t-BHQ showed similar activity as IPo. Taken together, our data suggest that Nrf2 activity, along with HO-1, plays an important role in the protective effects of IPo against IIR-induced acute lung injury.

  20. Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Lijuan [Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009 (China); Cardiovascular Disease, Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States); Wang, Yingjie [Cardiovascular Disease, Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States); Internal Medicine of Traditional Chinese Medicine, Shuguang Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Pan, Yaohua; Zhang, Lan [Cardiovascular Disease, Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States); Shen, Chengxing [Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University, Shanghai (China); Qin, Gangjian [Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 (United States); Ashraf, Muhammad [Pathology and Lab Med, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States); Weintraub, Neal [Cardiovascular Disease, Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States); Ma, Genshan, E-mail: magenshan@hotmail.com [Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009 (China); Tang, Yaoliang, E-mail: tangyg@ucmail.uc.edu [Cardiovascular Disease, Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States)

    2013-02-15

    Highlights: ► Cardiac progenitor-derived (CPC) Exosomes protect H9C2 from apoptosis in vitro. ► CPC-exosomes protect cardiomyoyctes from MI/R induced apoptosis in vivo. ► CPC-exosomes were taken up by H9C2 with high efficiency using PKH26 labeling. ► miR-451, one of GATA4-responsive miRNA cluster, is enriched in CPC-exosomes. -- Abstract: Background: Cardiac progenitors (CPC) mediate cardioprotection via paracrine effects. To date, most of studies focused on secreted paracrine proteins. Here we investigated the CPC-derived-exosomes on protecting myocardium from acute ischemia/reperfusion (MI/R) injury. Methods and results: CPC were isolated from mouse heart using two-step protocol. Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker. qRT-PCR shows that CPC-exosomes have high level expression of GATA4-responsive-miR-451. Exosomes were ex vivo labeled with PKH26, We observed exosomes can be uptaken by H9C2 cardiomyoblasts with high efficiency after 12 h incubation. CPC-exosomes protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation invitro. In vivo delivery of CPC-exosomes in an acute mouse myocardial ischemia/reperfusion model inhibited cardiomyocyte apoptosis by about 53% in comparison with PBS control (p < 0.05). Conclusion: Our results suggest, for the first time, the CPC-exosomes can be used as a therapeutic vehicle for cardioprotection, and highlights a new perspective for using non-cell exosomes for cardiac disease.

  1. Bone marrow-derived myofibroblasts contribute to the renal interstitial myofibroblast population and produce procollagen I after ischemia/reperfusion in rats

    NARCIS (Netherlands)

    Broekema, Martine; Harmsen, Martin C.; van Luyn, Marja J. A.; Koerts, Jasper A.; Petersen, Arjen H.; van Kooten, Theo G.; van Goor, Harry; Navis, Gerjan; Popa, Eliane R.

    Bone marrow-derived cells (BMDC) have been proposed to exert beneficial effects after renal ischemia/reperfusion injury (IRI) by engraftment in the tubular epithelium. However, BMDC can give rise to myofibroblasts and may contribute to fibrosis. BMDC contribution to the renal interstitial

  2. Bone marrow-derived myofibroblasts contribute to the renal interstitial myofibroblast population and produce procollagen I after ischemia/reperfusion in rats

    NARCIS (Netherlands)

    Broekema, Martine; Harmsen, Martin C.; van Luyn, Marja J. A.; Koerts, Jasper A.; Petersen, Arjen H.; van Kooten, Theo G.; van Goor, Harry; Navis, Gerjan; Popa, Eliane R.

    2007-01-01

    Bone marrow-derived cells (BMDC) have been proposed to exert beneficial effects after renal ischemia/reperfusion injury (IRI) by engraftment in the tubular epithelium. However, BMDC can give rise to myofibroblasts and may contribute to fibrosis. BMDC contribution to the renal interstitial myofibrobl

  3. Atherosclerotic ischemic renal disease. Diagnosis and prevalence in an hypertensive and/or uremic elderly population

    Directory of Open Access Journals (Sweden)

    Rossi Michele

    2003-02-01

    Full Text Available Abstract Background Atherosclerotic ischemic renal disease is a frequent cause of end-stage renal failure leading to dialysis among the elderly; Its prevalence is inferred from autopsy or retrospective arteriographic studies. This study has been conducted on 269 subjects over 50 with hypertension and/or CRF, unrelated to other known causes of renal disease. Methods All 269 patients were studied either by color-flow duplex sonography (n = 238 or by renal scintigraphy (n = 224, and 199 of the 269 patients were evaluated using both of these techniques. 40 patients, found to have renal artery stenosis (RAS, were subjected to 3D-contrast enhancement Magnetic Resonance Angiography (MRA and/or Selective Angiography (SA. An additional 23 cases, negative both to scintigraphy and to ultrasound study, underwent renal angiography (MRA and/or SA. Results Color-duplex sonography, carried out in 238 patients, revealed 49 cases of RAS. MR or SA was carried out in 35 of these 49 patients, and confirmed the diagnosis in 33. Color-duplex sonography showed a PPV value of 94.3% and NPV of 87.0% while renal scintigraphy, carried out in 224 patients, had a PPV of 72.2% and a NPV of 29.4%. Patients with RAS showed a higher degree of renal insufficiency compared to non stenotic patients while there were no differences in proteinuria. RAS, based on color-duplex sonography studies, was present in 11% of patients in the age group 50–59, 18% in the 60–69 and 23% at age 70 and above. Conclusions A relatively large percentage of the elderly population with renal insufficiency and/or hypertension is affected by RAS and is at risk of developing end-stage renal failure. Color-duplex ultrasonography is a valid routine method of investigation of population at risk for renal artery stenosis.

  4. Efeito do uso da tadalafila, inibidor da fosfodiesterase tipo 5, na isquemia-reperfusão renal : estudo experimental em suínos

    OpenAIRE

    Cláudio Miguel Pinto Morales

    2010-01-01

    Objetivo: Avaliar os efeitos da tadalafila, um inibidor da fosfodiesterase tipo 5, nos valores teciduais renais de malondialdeído (produto da lipoperoxidação celular), nos níveis séricos de uréia e creatinina e na histologia renal em suínos submetidos à isquemia-reperfusão renal em rim único. Material e métodos: Doze suínos Large-White foram submetidos à uninefrectomia seguida por isquemia-reperfusão renal contralateral e separados aleatoriamente em dois grupos com ou sem tratamento com tadal...

  5. Meclofenamate elicits a nephropreventing effect in a rat model of ischemic acute kidney injury by suppressing indoxyl sulfate production and restoring renal organic anion transporters

    Directory of Open Access Journals (Sweden)

    Saigo C

    2014-08-01

    with the inhibition of I/R-evoked elevation of prostaglandin E2. Our results suggest that meclofenamate inhibits hepatic sulfotransferase-mediated production of IS, thereby suppressing serum and renal accumulation of IS. Meclofenamate also prevents the prostaglandin E2-dependent downregulation of rOAT1 and rOAT3 expression. In conclusion, meclofenamate was found to elicit a nephropreventive effect in ischemic acute kidney injury. Keywords: uremic toxins, hepatic sulfotransferase, renal ischemia/reperfusion, renal tubular cell

  6. Effect of renal revascularization on the development of renal dysfunction in atherosclerotic ischemic nephropathy

    OpenAIRE

    Rodrigo Hagemann; Vanessa dos Santos Silva; Roberto Jorge da Silva Franco; Pasqual Barretti; Luis Cuadrado Martin

    2014-01-01

    Chronic kidney disease (CKD) is characterized by a progressive loss of renal function and its main causes are hypertension and diabetes mellitus. Among the causes of hypertension is atherosclerotic renal disease (ARD). The development of CKD in patients with ARD appears to be due not only to the involvement of the main renal arteries, but also of the renal microcirculation, which may explain the fact that the success of the procedure does not guarantee an improvement in the progression of CKD...

  7. Effect of Leukocytes Transfer on the Induction of Liver Damage after Renal Ischemia- Reperfusion in Inbred Mice

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    Hossein Khastar

    2012-07-01

    Full Text Available Introduction: Renal ischemia-reperfusion (IR induces organ damage in remote organs such as liver, brain and lung. The aim of this study was to assess the role of leukocytes in the induction of liver damage after renal IR injury.Methods: Inbred mice were subjected to either sham operation or bilateral renal IR injury (60 min ischemia followed by 3h reperfusion. Mice were then anesthetized for collection of leukocytes by heart puncture. Isolated leukocytes were transferred to two other groups: intact recipient mice that received leukocytes from IR mice and intact recipient mice that received leukocytes from sham-operated control mice. After 24h, recipient mice were anesthetized and blood and hepatic samples were collected.Results: Alanine aminotransferase (ALT, aspartate aminotransferase (AST and hepatic malondialdehyde (MDA increased significantly in intact recipient mice that received leukocytes from IR mice in comparison to intact recipient mice receiving leukocytes from sham-operated control mice. In addition, loss of normal liver architecture, cytoplasmic vacuolization and focal infiltration of leukocytes were observed.Conclusion: These results suggest that leukocytes are one of the possible factors that contribute to liver damage after renal IR injury and this damage is partly due to the induction of oxidative stress.

  8. Pre-ischemic mitochondrial substrate constraint by inhibition of malate-aspartate shuttle preserves mitochondrial function after ischemia-reperfusion

    DEFF Research Database (Denmark)

    Jespersen, Nichlas Riise; Yokota, Takashi; Støttrup, Nicolaj Brejnholt

    2017-01-01

    and early reperfusion by AOA treatment could prevent mitochondrial damage at later reperfusion. The AOA treatment preserved mitochondrial respiratory capacity with reduced mitochondrial oxidative stress during late reperfusion to the same extent as ischaemic preconditioning (IPC). However, AOA treatment...... of mitochondrial function during late reperfusion in an IR-injured heart. ABSTRACT: Mitochondrial dysfunction plays a central role in ischaemia-reperfusion (IR) injury. Pre-ischaemic administration of aminooxyacetate (AOA), an inhibitor of the malate-aspartate shuttle (MAS), provides cardioprotection against IR...... injury, although the underlying mechanism remains unknown. We hypothesized that a transient inhibition of the MAS during ischaemia and early reperfusion could preserve mitochondrial function at later phase of reperfusion in the IR-injured heart to the same extent as ischaemic preconditioning (IPC), which...

  9. Change of CD11a and myeloperoxidase content during rat renal ischemia-reperfusion injury%肾缺血再灌注损伤中CD11a及髓过氧化酶的变化

    Institute of Scientific and Technical Information of China (English)

    洪伟; 王禾; 石炳毅; 沈瑞雄; 柏宏伟; 李州利; 周文强

    2003-01-01

    AIM:To investigate the change of CD11a and myeloperoxidase(MPO) content during rat renal ischemia-reperfusion injury(IRI),as well as the role of LFA-1 in renal IRI.METHODS:We utillzed the rat model of renal IRI to detect the renal tissue contents of CD11a and MPO.RESULT:Level of CD11a and MPO was very low in normal renal tissue,but was increased significantiy in those of ischemia reperfusion.And this level in the ischemia 60 min reperfusion group was higher than that in ischemia 30 min reperfusion group.CONCLUSION:Level of CD11a and MPO in rat renal tissue increased dignificantly during rat renal IRI.LFAK-1 mediated leukocyte adherence plays an important role in renal IRI.

  10. New α-lipoic acid derivative, DHL-HisZn, ameliorates renal ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Koga, Hironori; Hagiwara, Satoshi; Kusaka, Jyunya; Goto, Koji; Uchino, Tetyuya; Shingu, Chihiro; Kai, Shinya; Noguchi, Takayuki

    2012-05-15

    Ischemia-reperfusion (I/R) occurs frequently in a variety of clinical settings, such as renal transplantation. In addition, I/R is a major cause of acute kidney injury (AKI). A recent study has reported that reactive oxygen species (ROS) are important mediators of AKI, suggesting that reducing ROS generation may prevent renal injury. The present study evaluated the ability of DHL-HisZn, a new α-lipoic acid derivative, to inhibit ROS generation and prevent renal I/R injury in rats. Rats received an intravenous infusion of DHL-HisZn or saline, and then underwent experimentally induced renal I/R injury or sham treatment. Rats were sacrificed after 60 min of ischemia and 24 h of reperfusion. To evaluate the renal protective effects of DHL-HisZn, serum blood urea nitrogen (BUN) and creatinine (Cre) concentrations were determined, kidneys were histologically assessed, and malondialdehyde (MDA), a biomarker of oxidative stress, was evaluated. In addition, antimycin A (AMA)-stimulated RAW264.7 cells were treated with DHL-HisZn to assess its antioxidant effects in vitro. DHL-HisZn treatment attenuated I/R-induced histologic alterations, reduced serum levels of serum BUN and Cre, and decreased MDA levels in the kidneys of rats with renal I/R injury. Furthermore, DHL-HisZn decreased ROS levels in AMA-stimulated RAW264.7 cells. Our in vitro and in vivo findings suggest that DHL-HisZn may have therapeutic potential against various human I/R conditions. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Effects of alprostadil and iloprost on renal, lung, and skeletal muscle injury following hindlimb ischemia–reperfusion injury in rats

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    Erer D

    2016-08-01

    Full Text Available Dilek Erer,1,* Abdullah Özer,1,* Hüseyin Demirtaş,1 İpek Işık Gönül,2 Halil Kara,3 Hande Arpacı,4 Faruk Metin Çomu,5 Gürsel Levent Oktar,1 Mustafa Arslan,6 Ayşegül Küçük7 1Department of Cardiovascular Surgery, 2Department of Pathology, Gazi University Medical Faculty, 3Department of Pharmacology, Yıldırım Beyazıt University Medical Faculty, 4Department of Oral and Maxillofacial Surgery, Ankara University Faculty of Dentistry, Besevler, Ankara, 5Department of Physiology, Kırıkkale University Medical Faculty, Kırıkkale, 6Department of Anesthesiology and Reanimation, Gazi University Medical Faculty, Ankara, 7Department of Physiology, Dumlupınar University Medical Faculty, Kütahya, Turkey *These authors contributed equally to this work Objectives: To evaluate the effects of alprostadil (prostaglandin [PGE1] analog and iloprost (prostacyclin [PGI2] analog on renal, lung, and skeletal muscle tissues after ischemia reperfusion (I/R injury in an experimental rat model.Materials and methods: Wistar albino rats underwent 2 hours of ischemia via infrarenal aorta clamping with subsequent 2 hours of reperfusion. Alprostadil and iloprost were given starting simultaneously with the reperfusion period. Effects of agents on renal, lung, and skeletal muscle (gastrocnemius tissue specimens were examined.Results: Renal medullary congestion, cytoplasmic swelling, and mean tubular dilatation scores were significantly lower in the alprostadil-treated group than those found in the I/R-only group (P<0.0001, P=0.015, and P<0.01, respectively. Polymorphonuclear leukocyte infiltration, pulmonary partial destruction, consolidation, alveolar edema, and hemorrhage scores were significantly lower in alprostadil- and iloprost-treated groups (P=0.017 and P=0.001; P<0.01 and P<0.0001. Polymorphonuclear leukocyte infiltration scores in skeletal muscle tissue were significantly lower in the iloprost-treated group than the scores found in the nontreated I

  12. Deficiency for the chemokine monocyte chemoattractant protein-1 aggravates tubular damage after renal ischemia/reperfusion injury.

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    Ingrid Stroo

    Full Text Available Temporal expression of chemokines is a crucial factor in the regulation of renal ischemia/reperfusion (I/R injury and repair. Beside their role in the migration and activation of inflammatory cells to sites of injury, chemokines are also involved in other processes such as angiogenesis, development and migration of stem cells. In the present study we investigated the role of the chemokine MCP-1 (monocyte chemoattractant protein-1 or CCL2, the main chemoattractant for monocytes, during renal I/R injury. MCP-1 expression peaks several days after inducing renal I/R injury coinciding with macrophage accumulation. However, MCP-1 deficient mice had a significant decreased survival and increased renal damage within the first two days, i.e. the acute inflammatory response, after renal I/R injury with no evidence of altered macrophage accumulation. Kidneys and primary tubular epithelial cells from MCP-1 deficient mice showed increased apoptosis after ischemia. Taken together, MCP-1 protects the kidney during the acute inflammatory response following renal I/R injury.

  13. Deficiency for the chemokine monocyte chemoattractant protein-1 aggravates tubular damage after renal ischemia/reperfusion injury.

    Science.gov (United States)

    Stroo, Ingrid; Claessen, Nike; Teske, Gwendoline J D; Butter, Loes M; Florquin, Sandrine; Leemans, Jaklien C

    2015-01-01

    Temporal expression of chemokines is a crucial factor in the regulation of renal ischemia/reperfusion (I/R) injury and repair. Beside their role in the migration and activation of inflammatory cells to sites of injury, chemokines are also involved in other processes such as angiogenesis, development and migration of stem cells. In the present study we investigated the role of the chemokine MCP-1 (monocyte chemoattractant protein-1 or CCL2), the main chemoattractant for monocytes, during renal I/R injury. MCP-1 expression peaks several days after inducing renal I/R injury coinciding with macrophage accumulation. However, MCP-1 deficient mice had a significant decreased survival and increased renal damage within the first two days, i.e. the acute inflammatory response, after renal I/R injury with no evidence of altered macrophage accumulation. Kidneys and primary tubular epithelial cells from MCP-1 deficient mice showed increased apoptosis after ischemia. Taken together, MCP-1 protects the kidney during the acute inflammatory response following renal I/R injury.

  14. Inhibition of Notch signaling by Dll4-Fc promotes reperfusion of acutely ischemic tissues

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ren [Department of Pathology, University of Southern California, Los Angeles (United States); Trindade, Alexandre [Centro Interdisciplinar de Investigacao em Sanidade Animal (CIISA), Lisbon Technical University, Lisbon (Portugal); Instituto Gulbenkian de Ciencia, Oeiras (Portugal); Sun, Zhanfeng [Department of Vascular Surgery, 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang (China); Kumar, Ram; Weaver, Fred A. [Department of Surgery, University of Southern California, Los Angeles (United States); Krasnoperov, Valery; Naga, Kranthi [Vasgene Therapeutics, Los Angeles, CA (United States); Duarte, Antonio [Centro Interdisciplinar de Investigacao em Sanidade Animal (CIISA), Lisbon Technical University, Lisbon (Portugal); Instituto Gulbenkian de Ciencia, Oeiras (Portugal); Gill, Parkash S., E-mail: parkashg@usc.edu [Department of Pathology, University of Southern California, Los Angeles (United States)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer Low dose Dll4-Fc increases vascular proliferation and overall perfusion. Black-Right-Pointing-Pointer Low dose Dll4-Fc helps vascular injury recovery in hindlimb ischemia model. Black-Right-Pointing-Pointer Low dose Dll4-Fc helps vascular injury recovery in skin flap model. Black-Right-Pointing-Pointer Dll4 heterozygous deletion promotes vascular injury recovery. Black-Right-Pointing-Pointer Dll4 overexpression delays vascular injury recovery. -- Abstract: Notch pathway regulates vessel development and maturation. Dll4, a high-affinity ligand for Notch, is expressed predominantly in the arterial endothelium and is induced by hypoxia among other factors. Inhibition of Dll4 has paradoxical effects of reducing the maturation and perfusion in newly forming vessels while increasing the density of vessels. We hypothesized that partial and/or intermittent inhibition of Dll4 may lead to increased vascular response and still allow vascular maturation to occur. Thus tissue perfusion can be restored rapidly, allowing quicker recovery from ischemia or tissue injury. Our studies in two different models (hindlimb ischemia and skin flap) show that inhibition of Dll4 at low dose allows faster recovery from vascular and tissue injury. This opens a new possibility for Dll4 blockade's therapeutic application in promoting recovery from vascular injury and restoring blood supply to ischemic tissues.

  15. Strophanthus hispidus attenuates the Ischemia-Reperfusion induced myocardial Infarction and reduces mean arterial pressure in renal artery occlusion

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    Rohit Gundamaraju

    2014-01-01

    Full Text Available Background: The myocardium is generally injured in the case of reperfusion injury and arterial damage is caused by hypertension. In reference to these statements, the present study was focused. Cardiac glycosides were said to have protective effects against myocardial infarction and hypertension. Strophanthus hispidus was thus incorporated in the study. Objective: The prime objective of the study was to investigate the protective effects of Strophanthus hispidus against ischemia-reperfusion myocardial Infarction and renal artery occluded hypertension in rats. Materials and Methods: The animal model adopted was surgically-induced myocardial ischemia, performed by means of left anterior descending coronary artery occlusion (LAD for 30 min followed by reperfusion for another 4 h. Infarct size was assessed by using the staining agent TTC (2,3,5-triphenyl tetrazolium chloride. Hypertension was induced by clamping the renal artery with renal bulldog clamp for 4 h. Results: The study was fruitful by the effect of Strophanthus hispidus on infarction size, which got reduced to 27.2 ± 0.5and 20.0 ± 0.2 by 500 mg/Kg and 1000 mg/Kg ethanolic extracts which was remarkably significant when compared with that of the control group 52.8 ± 4.6. The plant extract did reduce heart rate at various time intervals. There was also a protective effect in the case of mean arterial blood pressure were the 500 mg/Kg and 1000 mg/Kg of the plant extract did reduce the hypertension after 60 minutes was 60.0 ± 4.80 and 50.50 ± 6.80. Conclusion: The results suggest that 500 mg/Kg and 100 mg/Kg ethanolic extract of Strophanthus hispidus was found to possess significant cardiac protective and anti-hypertensive activity.

  16. Evaluation of the gender difference in the protective effects of ischemic postconditioning on ischemia-reperfusion-induced acute kidney injury in rats

    Directory of Open Access Journals (Sweden)

    Atefeh Mahmoudi

    2013-11-01

    Full Text Available Background: Several studies indicate that gender differences exist in tolerance of the kidney to ischemia reperfusion (IR injury. Recently, postconditioning (POC, induction of brief repetitive periods of IR, has been introduced to reduce the extent of the damage to the kidney. This method was shown to attenuate renal IR injury by modifying oxidative stress and reducing lipid peroxidation. Considering the gender effect on the results of several treatment methods, in this study, we investigated the impact of gender on the protective effect of POC on the rat kidney.Methods: In this study, after right nephrectomy, 48 male and female rats were randomly divided into 6 groups of 8 rats: In IR group, with the use of bulldog clamp, 45 minutes of left renal artery ischemia was induced followed by 24 hours of reperfusion. In the sham group, all of the above surgical procedures were applied except that IR was not induced. In the POC group, after the induction of 45 minutes ischemia, 4 cycles of 10 seconds of intermittent ischemia and reperfusion were applied before restoring of blood to the kidney. 24 hours later, serum and renal tissue samples were collected for renal functional monitoring and oxidative stress evaluation.Results: Postconditioning attenuated renal dysfunction considering the significant decrease in plasma creatinine and BUN compared with IR group only in male rats (P<0.05. Also, POC attenuated oxidative stress in male rats’ kidney tissues as demonstrated by a significantly reduced malondialdehyde (MDA level and increased superoxide dismutase (SOD activity (P<0.05. In female rats, there were no changes in functional markers and oxidative stress status in POC group compared to IR group. Conclusion: Considering gender difference, POC had protective effect against IR injury by attenuating functional and oxidative stress markers in male rat kidneys. This protective effect was not seen in female rats.

  17. Hybrid approach of ventricular assist device and autologous bone marrow stem cells implantation in end-stage ischemic heart failure enhances myocardial reperfusion

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    Khayat Andre

    2011-01-01

    Full Text Available Abstract We challenge the hypothesis of enhanced myocardial reperfusion after implanting a left ventricular assist device together with bone marrow mononuclear stem cells in patients with end-stage ischemic cardiomyopathy. Irreversible myocardial loss observed in ischemic cardiomyopathy leads to progressive cardiac remodelling and dysfunction through a complex neurohormonal cascade. New generation assist devices promote myocardial recovery only in patients with dilated or peripartum cardiomyopathy. In the setting of diffuse myocardial ischemia not amenable to revascularization, native myocardial recovery has not been observed after implantation of an assist device as destination therapy. The hybrid approach of implanting autologous bone marrow stem cells during assist device implantation may eventually improve native cardiac function, which may be associated with a better prognosis eventually ameliorating the need for subsequent heart transplantation. The aforementioned hypothesis has to be tested with well-designed prospective multicentre studies.

  18. Classical and remote post-conditioning effects on ischemia/reperfusion-induced acute oxidant kidney injury.

    Science.gov (United States)

    Kadkhodaee, Mehri; Najafi, Atefeh; Seifi, Behjat

    2014-11-01

    The present study aimed to analyze and compare the effects of classical and remote ischemic postconditioning (POC) on rat renal ischemia/reperfusion (IR)-induced acute kidney injury. After right nephrectomy, male rats were randomly assigned into four groups (n = 8). In the IR group, 45 min of left renal artery occlusion was induced followed by 24 h of reperfusion. In the classical POC group, after induction of 45 min ischemia, 4 cycles of 10 s of intermittent ischemia and reperfusion were applied to the kidney before complete restoring of renal blood. In the remote POC group, 4 cycles of 5 min ischemia and reperfusion of left femoral artery were applied after 45 min renal ischemia and right at the time of renal reperfusion. There was a reduction in renal function (increase in blood urea and creatinine) in the IR group. Application of both forms of POC prevented the IR-induced reduction in renal function and histology. There were also significant improvements in kidney oxidative stress status in both POC groups demonstrated by a reduction in malondialdehyde (MDA) formation and preservation of antioxidant levels comparing to the IR group. We concluded that both methods of POC have protective effects on renal function and histology possibly by a reduction in IR-induced oxidative stress.

  19. C-reactive protein exacerbates renal ischemia-reperfusion injury: are myeloid-derived suppressor cells to blame?

    Science.gov (United States)

    Pegues, Melissa A; McWilliams, Ian L; Szalai, Alexander J

    2016-07-01

    Myeloid-derived suppressor cells (MDSCs) are a CD11b(+)Gr1(+) population in mice that can be separated into granulocytic (g-MDSC) and monocytic (m-MDSC) subtypes based on their expression of Ly6G and Ly6C. Both MDSC subtypes are potent suppressors of T cell immunity, and their contribution has been investigated in a plethora of diseases including renal cancer, renal transplant, and chronic kidney disease. Whether MDSCs contribute to the pathogenesis of acute kidney injury (AKI) remains unknown. Herein, using human C-reactive protein (CRP) transgenic (CRPtg) and CRP-deficient mice (CRP(-/-)) subjected to bilateral renal ischemia-reperfusion injury (IRI), we confirm our earlier finding that CRP exacerbates renal IRI and show for the first time that this effect is accompanied in CRPtg mice by a shift in the balance of kidney-infiltrating MDSCs toward a suppressive Ly6G(+)Ly6C(low) g-MDSC subtype. In CRPtg mice, direct depletion of g-MDSCs (using an anti-Gr1 monoclonal antibody) reduced the albuminuria caused by renal IRI, confirming they play a deleterious role. Remarkably, treatment of CRPtg mice with an antisense oligonucleotide that specifically blocks the human CRP acute-phase response also led to a reduction in renal g-MDSC numbers and improved albuminuria after renal IRI. Our study in CRPtg mice provides new evidence that MDSCs participate in the pathogenesis of renal IRI and shows that their pharmacological depletion is beneficial. If ongoing investigations confirm that CRP is an endogenous regulator of MDSCs in CRPtg mice, and if this action is recapitulated in humans, then targeting CRP or/and MDSCs might offer a new approach for the treatment of AKI.

  20. Fetal Kidney Cells Can Ameliorate Ischemic Acute Renal Failure in Rats through Their Anti-Inflammatory, Anti-Apoptotic and Anti-Oxidative Effects.

    Science.gov (United States)

    Gupta, Ashwani Kumar; Jadhav, Sachin H; Tripathy, Naresh Kumar; Nityanand, Soniya

    2015-01-01

    Fetal kidney cells may contain multiple populations of kidney stem cells and thus appear to be a suitable cellular therapy for the treatment of acute renal failure (ARF) but their biological characteristics and therapeutic potential have not been adequately explored. We have culture expanded fetal kidney cells derived from rat fetal kidneys, characterized them and evaluated their therapeutic effect in an ischemia reperfusion (IR) induced rat model of ARF. The fetal kidney cells grew in culture as adherent spindle shaped/polygonal cells and expressed CD29, CD44, CD73, CD90, CD105, CD24 and CD133 markers. Administration of PKH26 labeled fetal kidney cells in ARF rats resulted in a significant decrease in the levels of blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin and decreased tubular necrosis in the kidney tissues (pkidney cells were observed to engraft around injured tubular cells, and there was increased proliferation and decreased apoptosis of tubular cells in the kidneys (pkidney tissues of ARF rats treated with fetal kidney cells had a higher gene expression of renotropic growth factors (VEGF-A, IGF-1, BMP-7 and bFGF) and anti-inflammatory cytokine (IL10); up regulation of anti-oxidative markers (HO-1 and NQO-1); and a lower Bax/Bcl2 ratio as compared to saline treated rats (pkidney cells express mesenchymal and renal progenitor markers, and ameliorate ischemic ARF predominantly by their anti-apoptotic, anti-inflammatory and anti-oxidative effects.

  1. Compensatory renal growth and mitochondrial function: the influence of warm ischemia and reperfusion Hipertrofia renal compensatória e função mitocondrial: influência da isquemia quente e reperfusão

    Directory of Open Access Journals (Sweden)

    Silvio Tucci Jr

    2008-01-01

    Full Text Available PURPOSE: To evaluate the influence of ischemia/reperfusion injury on renal compensatory growth (CGR and mitochondrial function. METHODS: Forty five Wistar rats were divided in 3 groups: Control Group (GC - 21 rats were submitted to a sham laparotomy and sacrificed at 1st (6 rats and 7th (15 rats postoperative days to evaluate the dry weight of both kidneys and their growth during 1 week (6 rats and to quantify mitochondrial respiration (9 rats; Group 1 (G1 - 12 rats underwent right nephrectomy and were sacrificed 7 days later for analysis of renal mitochondrial function (6 rats and dry weight (6 rats. Group 2 (G2 - renal warm ischemia for 60 minutes followed by right nephrectomy was performed in 12 rats; they were sacrificed 7 days later to evaluate renal mitochondrial function (6 rats and dry weight (6 rats. RESULTS: Dry weight (mg of left kidneys at 7th day: GC - 219±18, G1 - 281±23 and G2 - 338±39 (GCxG1 p0.05. State 3 respirations (mM/min/mg in GC, G1 and G2 was respectively: 99±23, 132±22 and 82±44 (pOBJETIVO: Avaliar a influência da lesão de isquemia/reperfusão na hipertrofia renal compensatória (HRC e na função mitocondrial. MÉTODOS: 45 ratos Wistar foram divididos em três grupos: Grupo Controle (GC - 21 ratos submetidos apenas à laparotomia e sacrificados no 1º dia (6 ratos e 7º dia pós-operatório (15 ratos para avaliar o peso seco de ambos os rins e seu crescimento durante uma semana (6 ratos e quantificar a função mitocondrial (9 ratos; Grupo 1 (G1 - 12 ratos submetidos à nefrectomia direita e sacrificados após 7 dias para análise da função mitocondrial renal (6 ratos e peso renal seco (6 ratos; Grupo 2 (G2 - isquemia renal quente durante 60 minutos no rim esquerdo seguida da nefrectomia direita foi realizada em 12 ratos, que foram sacrificados após 7 dias para avaliação da função mitocondrial (6 ratos e peso seco (6 ratos. RESULTADOS: peso seco (mg do rim esquerdo no 7º dia: GC= 219±18; G1=281±23 e G2

  2. Intravenous renal cell transplantation with SAA1-positive cells prevents the progression of chronic renal failure in rats with ischemic-diabetic nephropathy.

    Science.gov (United States)

    Kelly, Katherine J; Zhang, Jizhong; Han, Ling; Wang, Mingsheng; Zhang, Shaobo; Dominguez, Jesus H

    2013-12-15

    Diabetic nephropathy, the most common cause of progressive chronic renal failure and end-stage renal disease, has now reached global proportions. The only means to rescue diabetic patients on dialysis is renal transplantation, a very effective therapy but severely limited by the availability of donor kidneys. Hence, we tested the role of intravenous renal cell transplantation (IRCT) on obese/diabetic Zucker/SHHF F1 hybrid (ZS) female rats with severe ischemic and diabetic nephropathy. Renal ischemia was produced by bilateral renal clamping of the renal arteries at 10 wk of age, and IRCT with genetically modified normal ZS male tubular cells was given intravenously at 15 and 20 wk of age. Rats were euthanized at 34 wk of age. IRCT with cells expressing serum amyloid A had strong and long-lasting beneficial effects on renal function and structure, including tubules and glomeruli. However, donor cells were found engrafted only in renal tubules 14 wk after the second infusion. The results indicate that IRCT with serum amyloid A-positive cells is effective in preventing the progression of chronic kidney disease in rats with diabetic and ischemic nephropathy.

  3. Effect of renal function status on the prognostic value of heart rate in acute ischemic stroke patients.

    Science.gov (United States)

    Zhu, Zhengbao; Zhong, Chongke; Xu, Tian; Wang, Aili; Peng, Yanbo; Xu, Tan; Peng, Hao; Chen, Chung-Shiuan; Wang, Jinchao; Ju, Zhong; Li, Qunwei; Geng, Deqin; Sun, Yingxian; Du, Qingjuan; Li, Yongqiu; Chen, Jing; Zhang, Yonghong; He, Jiang

    2017-08-01

    The association between heart rate and prognosis of ischemic stroke remains debatable, and whether renal function status influences the relationship between them is still not elucidated. A total of 3923 ischemic stroke patients were included in this prospective multicenter study from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at 3 months after stroke. Secondary outcomes were, separately, death and major disability. The association between heart rate tertiles and primary outcome was appreciably modified by renal function status (pinteraction = 0.037). After multivariate adjustment, high heart rate was associated with increased risk of primary outcome in patients with abnormal renal function (odds ratio, 1.61; 95% confidence interval, 1.02-2.54; ptrend = 0.039) but not in patients with normal renal function (odds ratio, 0.96; 95% confidence interval, 0.75-1.23; ptrend = 0.741), when two extreme tertiles were compared. Each 10 bpm increase of heart rate was associated with 21% (95% CI: 1%-44%) increased risk of primary outcome, and a linear association between heart rate and risk of primary outcome was observed among patients with abnormal renal function (p for linearity = 0.002). High heart rate may be merely a strong predictor of poor prognosis in acute ischemic stroke patients with abnormal renal function, suggesting that heart rate reduction should be applied to ischemic stroke patients with abnormal renal function to improve their prognosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. 肾神经在肾缺血预处理对麻醉家兔心脏保护中的作用%Role of renal nerve in cardioprotection provided by renal ischemic preconditioning in anesthetized rabbits

    Institute of Scientific and Technical Information of China (English)

    丁延峰; 张蔓蔓; 何瑞荣

    2001-01-01

    The effects of renal ischemic preconditioning (RIP) on ischemia-reperfused myocardium were examined in the urethane-anesthetized rabbit to determine whether RIP may provide cardioprotection and to observe the role of the renal nerve in such condition. The results obtained are as follows: (1) During 45 min myocardial ischemia and subsequent 180 min reperfusion, blood pressure, heart rate and myocardial oxygen consumption decreased progressively. Epicardial electrographic ST-segment was elevated significantly in the period of ischemia and returned to the baseline gradually in the course of reperfusion. The myocardial infarct size occupied 55.80±1.25% of the area at risk. (2) RIP significantly reduced the myocardial infarct size to 36.51±2.80% (P<0.01), indicating the cardioprotective effect of such an intervention. (3) Renal nerve section (RNS) completely abolished the cardioprotection afforded by RIP, though RNS per se did not affect the myocardial infarct size produced by ischemia-reperfusion. (4) During 10 min renal ischemia, the averaged multi-unit discharge rate of the renal afferent was increased from 0.14±0.08 to 0.65±0.12 imp/s (P<0.01). (5) Pretreatment with an adenosine receptor antagonist 8-phenyltheophylline (10 mg/kg) markedly attenuated the discharge rate of the renal afferent induced by transient renal ischemia, implying that adenosine released in ischemic kidney activated the renal afferent. It is suggested that activation of renal afferents by transient renal ischemia-reperfusion plays an important role in the cardioprotection afforded by RIP.%在氨基甲酸乙酯麻醉家兔上, 观察肾脏缺血预处理(RIP)对缺血-再灌注心肌的影响, 旨在证实RIP对心肌有无保护效应, 并明确肾神经在其中的作用。所得结果如下: (1)在心脏45 min缺血和180 min再灌注过程中, 血压、心率和心肌耗氧量呈进行性下降;心外膜电图ST段在缺血期明显抬高, 再灌注过程中逐渐恢复到基础对照

  5. 肾脏缺血预处理对麻醉家兔心脏保护的神经机制%Involvement of neural mechanism in cardioprotection provided by renal ischemic preconditioniong in anesthetized rabbits

    Institute of Scientific and Technical Information of China (English)

    丁延峰; 史明珠; 牛新清; 李东亮; 何瑞荣

    2002-01-01

    目的探讨肾神经在肾脏缺血预处理(RIP)心肌保护中的作用.方法在麻醉家兔心肌缺血/再灌注(MIR)模型上,观察MIR和RIP对家兔血流动力学、心肌耗氧量、心外膜电图和心肌梗死范围的影响.结果在MIR过程中,血流动力学指标和心肌耗氧量均明显持续性降低;心外膜电图ST段在缺血期明显升高,再灌注过程中恢复到基础对照值.单纯MIR时的心肌梗塞范围占缺血心肌的(55.80±1.25)%,RIP后心肌梗塞范围为(36.51±2.8)%,较单纯MIR显著减少(P<0.01).肾神经切断后对MIR所致的心肌梗死范围无明显影响,但可取消RIP对心肌的保护效应.结论 RIP具有心肌保护作用,肾短暂缺血-再灌注所诱发的肾神经传入活动可能参与此心肌保护效应.%Objective To investigate the role of renal nerve in cardioprotection provided by renal ischemic preconditioning(RIP).Methods The effects of ischemia-reperfusion and RIP on the hemodynamics, myocardial oxygen consumption, epicardial electrography and infarct size were examined in anesthetized rabbit.Results During the 45 min of myocardial ischemia and 180 min of reperfusion, all hemodynamic parameters and myocardial oxygen consumption decreased progressively significantly. Epicardial electrographic ST-segment was elevated significantly during myocardial ischemia and return to baseline progressively in the course of reperfusion. The myocardial infarct size occupied 55.80±1.25% of area at risk,and RIP significantly reduced the myocardial infarct size to 36.51±2.80%(P<0.01). The renal nerve section (RNS) per se didn't affect myocardial infarct size produced by ischemia-reperfusion, while cardioprotection afforded by RIP was completely abolished by RNS.Conlusion RIP have the protective effect on heart, and activation of renal afferents by transient ischemia-reperfusion play an important role in such a cardioprotection.

  6. Effects of dexmedetomidine on renal tissue after lower limb ischemia reperfusion injury in streptozotocin induced diabetic rats

    Science.gov (United States)

    Erbatur, Meral Erdal; Sezen, Şaban Cem; Bayraktar, Aslıhan Cavunt; Arslan, Mustafa; Kavutçu, Mustafa; Aydın, Muhammed Enes

    2017-01-01

    ABSTRACT Aim: The aim of this study was to investigate whether dexmedetomidine – administered before ischemia – has protective effects against lower extremity ischemia reperfusion injury that induced by clamping and subsequent declamping of infra-renal abdominal aorta in streptozotocin-induced diabetic rats. Material and Methods: After obtaining ethical committee approval, four study groups each containing six rats were created (Control (Group C), diabetes-control (Group DM-C), diabetes I/R (Group DM-I/R), and diabetes-I/R-dexmedetomidine (Group DM-I/R-D). In diabetes groups, single-dose (55 mg/kg) streptozotocin was administered intraperitoneally. Rats with a blood glucose level above 250 mg/dl at the 72nd hour were accepted as diabetic. At the end of four weeks, laparotomy was performed in all rats. Nothing else was done in Group C and DM-C. In Group DM-I/R, ischemia reperfusion was produced via two-hour periods of clamping and subsequent declamping of infra-renal abdominal aorta. In Group DM-I/R-D, 100 μg/kg dexmedetomidine was administered intraperitoneally 30 minutes before ischemia period. At the end of reperfusion, period biochemical and histopathological evaluation of renal tissue specimen were performed. Results: Thiobarbituric acid reactive substance (TBARS), Superoxide dismutase (SOD), Nitric oxide synthase (NOS), Catalase (CAT) and Glutathion S transferase (GST) levels were found significantly higher in Group DM-I/R when compared with Group C and Group DM-C. In the dexmedetomidine-treated group, TBARS, NOS, CAT, and GST levels were significantly lower than those measured in the Group D-I/R. In histopathological evaluation, glomerular vacuolization (GV), tubular dilatation (TD), vascular vacuolization and hypertrophy (VVH), tubular cell degeneration and necrosis (TCDN), tubular hyaline cylinder (THC), leucocyte infiltration (LI), and tubular cell spillage (TCS) in Group DM-I/R were significantly increased when compared with the control group

  7. The calcium-binding protein complex S100A8/A9 has a crucial role in controlling macrophage-mediated renal repair following ischemia/reperfusion

    NARCIS (Netherlands)

    Dessing, M.C.; Tammaro, A.; Pulskens, W.P.C.; Teske, G.J.; Butter, L.M.; Claessen, N.; Eijk, M. van; Poll, T. van der; Vogl, T.; Roth, J.; Florquin, S.; Leemans, J.C.

    2015-01-01

    Upon ischemia/reperfusion (I/R)-induced injury, several damage-associated molecular patterns are expressed including the calcium-binding protein S100A8/A9 complex. S100A8/A9 can be recognized by Toll-like receptor-4 and its activation is known to deleteriously contribute to renal I/R-induced injury.

  8. Electroacupuncture stimulation of the brachial plexus trunk on the healthy side promotes brain-derived neurotrophic factor mRNA expression in the ischemic cerebral cortex of a rat model of cerebral ischemia/reperfusion injury.

    Science.gov (United States)

    Guo, Zongjun; Wang, Lumin

    2012-07-25

    A rat model of cerebral ischemia/reperfusion was established by suture occlusion of the left middle cerebral artery. In situ hybridization results showed that the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic rat cerebral cortex increased after cerebral ischemia/ reperfusion injury. Low frequency continuous wave electroacupuncture (frequency 2-6 Hz, current intensity 2 mA) stimulation of the brachial plexus trunk on the healthy (right) side increased the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic cerebral cortex 14 days after cerebral ischemia/reperfusion injury. At the same time, electroacupuncture stimulation of the healthy brachial plexus truck significantly decreased neurological function scores and alleviated neurological function deficits. These findings suggest that electroacupuncture stimulation of the brachial plexus trunk on the healthy (right) side can greatly increase brain-derived neurotrophic factor mRNA expression and improve neurological function.

  9. Electroacupuncture stimulation of the brachial plexus trunk on the healthy side promotes brain-derived neurotrophic factor mRNA expression in the ischemic cerebral cortex of a rat model of cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Zongjun Guo; Lumin Wang

    2012-01-01

    A rat model of cerebral ischemia/reperfusion was established by suture occlusion of the left middle cerebral artery. In situ hybridization results showed that the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic rat cerebral cortex increased after cerebral ischemia/ reperfusion injury. Low frequency continuous wave electroacupuncture (frequency 2-6 Hz, current intensity 2 mA) stimulation of the brachial plexus trunk on the healthy (right) side increased the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic cerebral cortex 14 days after cerebral ischemia/reperfusion injury. At the same time, electroacupuncture stimulation of the healthy brachial plexus truck significantly decreased neurological function scores and alleviated neurological function deficits. These findings suggest that electroacupuncture stimulation of the brachial plexus trunk on the healthy (right) side can greatly increase brain-derived neurotrophic factor mRNA expression and improve neurological function.

  10. Effect of renal and non-renal ischemia/reperfusion on cell-mediated immunity in organs and plasma

    DEFF Research Database (Denmark)

    Brøchner, Anne Craveiro; Dagnæs-Hansen, Frederik; Toft, Palle

    2010-01-01

    study, 80 mice were divided into four groups. The following surgeries were performed on the groups compared: bilateral renal I/R by clamping, unilateral renal ischemia, anesthesia only, and unilateral hind leg I/R. Half of the animals were killed after 2 h and the other half after 24 h. To assess...... following renal I/R. All kinds of I/R induced an upregulation of the adhesion molecule CD 11b and a downregulation of MHC II. Renal and non-renal I/R induced neutrophil infiltration in distant organs. Renal I/R does not induce a larger cell-mediated inflammatory response in blood and organs than non-renal I/R....

  11. Effects of specific interleukin-1β-converting enzyme inhibitor on ischemic acute renal failure in murine models

    Institute of Scientific and Technical Information of China (English)

    Hua-feng LIU; Dong LIANG; Li-ming WANG; Nan ZHOU; Cui-wei YAO; Tao HONG; De-shen TANG; Xiao-wen CHEN

    2005-01-01

    Aim: To study the effect of selective interleukin-1 β-converting enzyme (ICE,caspase-1) inhibitor on ischemic acute renal failure (ARF). Methods: Mouse models of ischemic ARF were treated with the specific ICE inhibitor AC-YVAD-CMK.A renal function assay and renal morphological studies were employed to estimate the renal protective effect of AC-YVAD-CMK. The survival rate of mouse models was also analyzed by a time series test. Furthermore, renal ICE activity,mature interleukin-18 (IL-18) protein expression and interferon-γ (IFN-γ) mRNA expression were also detected by fluorescent enzyme-linked immunosorbent assay (ELISA), ELISA, and semi-quantitative reverse transcription-polymerase chain reaction, respectively. Results: The levels of blood urea nitrogen (BUN) and serum creatinine (Scr) increased remarkably in the model controls compared with the sham-operated groups (P<0.01). Typical renal tubular necrosis was found in the model controls. Renal ICE activity, mature IL-18 protein expression, and IFN-γmRNA expression were also increased significantly in the model controls compared with the sham-operated groups. The levels of BUN and Scr in the AC-YVAD-CMK therapy group were decreased significantly compared with the untreated model controls (P<0.01). Renal tubulointerstitial lesion was also attenuated significantly (P<0.05). AC-YVAD-CMK therapy alleviated the clinical features of ARF, and increased the survival rate (P<0.01). Furthermore, AC-YVADCMK therapy also decreased ICE activity, mature IL-18 protein expression, and IFN-γ mRNA expression in renal tissue (P<0.05). Conclusion: The selective ICEinhibitor AC-YVAD-CMK can effectively protect the kidney from acute ischemic lesions. This protective effect is associated with decreased renal ICE activity and suppressed IL- 18 maturation and IFN-γ mRNA transcription.

  12. Recovery from renal ischemia-reperfusion injury is associated with altered renal hemodynamics, blunted pressure natriuresis, and sodium-sensitive hypertension.

    Science.gov (United States)

    Pechman, Kimberly R; De Miguel, Carmen; Lund, Hayley; Leonard, Ellen C; Basile, David P; Mattson, David L

    2009-11-01

    The present studies evaluated intrarenal hemodynamics, pressure natriuresis, and arterial blood pressure in rats following recovery from renal ischemia-reperfusion (I/R) injury. Acute I/R injury, induced by 40 min of bilateral renal arterial occlusion, resulted in an increase in plasma creatinine that resolved within a week. Following 5 wk of recovery on a 0.4% NaCl diet, the pressure-natriuresis response was assessed in anesthetized rats in which the kidney was denervated and extrarenal hormones were administered intravenously. Increasing renal perfusion pressure (RPP) from 107 to 141 mmHg resulted in a fourfold increase in urine flow and sodium excretion in sham control rats. In comparison, pressure diuresis and natriuresis were significantly attenuated in post-I/R rats. In sham rats, glomerular filtration rate (GFR) averaged 1.6 +/- 0.2 mlxmin(-1)xg kidney weight(-1) and renal blood flow (RBF) averaged 7.8 +/- 0.7 mlxmin(-1)xg kidney weight(-1) at RPP of 129 mmHg. Renal cortical blood flow, measured by laser-Doppler flowmetry, was well autoregulated whereas medullary blood flow and renal interstitial hydrostatic pressure increased directly with elevated RPP in sham rats. In contrast, GFR and RBF were significantly reduced whereas medullary perfusion and interstitial pressure demonstrated an attenuated response to RPP in post-I/R rats. Further experiments demonstrated that conscious I/R rats develop hypertension when sodium intake is increased. The present data indicate that the pressure-natriuretic-diuretic response in I/R rats is blunted because of a decrease in GFR and RBF and the depressed pressure-dependent increase in medullary blood flow and interstitial pressure.

  13. Activation of ERK accelerates repair of renal tubular epithelial cells, whereas it inhibits progression of fibrosis following ischemia/reperfusion injury.

    Science.gov (United States)

    Jang, Hee-Seong; Han, Sang Jun; Kim, Jee In; Lee, Sanggyu; Lipschutz, Joshua H; Park, Kwon Moo

    2013-12-01

    Extracellular signal-regulated kinase (ERK) signals play important roles in cell death and survival. However, the role of ERK in the repair process after injury remains to be defined in the kidney. Here, we investigated the role of ERK in proliferation and differentiation of tubular epithelial cells, and proliferation of interstitial cells following ischemia/reperfusion (I/R) injury in the mouse kidney. Mice were subjected to 30min of renal ischemia. Some mice were administered with U0126, a specific upstream inhibitor of ERK, daily during the recovery phase, beginning at 1day after ischemia until sacrifice. I/R caused severe tubular cell damage and functional loss in the kidney. Nine days after ischemia, the kidney was restored functionally with a partial restoration of damaged tubules and expansion of fibrotic lesions. ERK was activated by I/R and the activated ERK was sustained for 9days. U0126 inhibited the proliferation, basolateral relocalization of Na,K-ATPase and lengthening of primary cilia in tubular epithelial cells, whereas it enhanced the proliferation of interstitial cells and accumulation of extracellular matrix. Furthermore, U0126 elevated the expression of cell cycle arrest-related proteins, p21 and phospholylated-chk2 in the post-ischemic kidney. U0126 mitigated the post-I/R increase of Sec10 which is a crucial component of exocyst complex and an important factor in ciliogenesis and tubulogenesis. U0126 also enhanced the expression of fibrosis-related proteins, TGF-β1 and phosphorylated NF-κB after ischemia. Our findings demonstrate that activation of ERK is required for both the restoration of damaged tubular epithelial cells and the inhibition of fibrosis progression following injury.

  14. The presence of oxidized low-density lipoprotein and inducible nitric oxide synthase expression in renal damage after intestinal ischemia reperfusion

    Directory of Open Access Journals (Sweden)

    Gamze Yurdakan

    2012-01-01

    Full Text Available Intestinal ischemia/reperfusion (I/R is a complex phenomenon that causes destruction of both local and remote tissues. The objective of this study was to investigate the possible participation of oxidized low-density lipoproteins (oxLDLs and inducible nitric oxide synthase (iNOS expression in renal tissue damage after intestinal I/R. The superior mesenteric artery was blocked for 30 minutes, followed by 24 hours of reperfusion. At the end of the reperfusion period, renal tissues were removed; the presence of oxLDL, superoxide dismutase enzyme activity, malondialdehyde levels, and iNOS expression were evaluated. I/R resulted in positive oxLDL staining in renal tissue. Compared with control rats, tissue from the I/R group showed significantly higher malondialdehyde levels and lower superoxide dismutase enzyme activity. Strong and diffuse iNOS expression was present in the I/R group. Our findings support the hypothesis that I/R of intestinal tissue results in oxidative and nitrosative stress and enhances lipid peroxidation in the end organ. These data show that oxLDL accumulates in rat renal tissue after intestinal I/R. Antioxidant strategies may provide organ protection in patients with reperfusion injury, at least by affecting interactions with free radicals, nitric oxide, and oxLDL. This study demonstrates for the first time that oxLDL may play a role in renal tissue damage after intestinal I/R. Antioxidant strategies may be beneficial for protection from reperfusion injury.

  15. Insulin Preconditioning Elevates p-Akt and Cardiac Contractility after Reperfusion in the Isolated Ischemic Rat Heart

    Directory of Open Access Journals (Sweden)

    Tamaki Sato

    2014-01-01

    Full Text Available Insulin induces cardioprotection partly via an antiapoptotic effect. However, the optimal timing of insulin administration for the best quality cardioprotection remains unclear. We tested the hypothesis that insulin administered prior to ischemia provides better cardioprotection than insulin administration after ischemia. Isolated rat hearts were prepared using Langendorff method and divided into three groups. The Pre-Ins group (Pre-Ins received 0.5 U/L insulin prior to 15 min no-flow ischemia for 20 min followed by 20 min of reperfusion. The Post-Ins group (Post-Ins received 0.5 U/L insulin during the reperfusion period only. The control group (Control was perfused with KH buffer throughout. The maximum of left ventricular derivative of pressure development (dP/dt(max was recorded continuously. Measurements of TNF-α and p-Akt in each time point were assayed by ELISA. After reperfusion, dP/dt(max in Pre-Ins was elevated, compared with Post-Ins at 10 minutes after reperfusion and Control at all-time points. TNF-α levels at 5 minutes after reperfusion in the Pre-Ins were lower than the others. After 5 minutes of reperfusion, p-Akt was elevated in Pre-Ins compared with the other groups. Insulin administration prior to ischemia provides better cardioprotection than insulin administration only at reperfusion. TNF-α suppression is possibly mediated via p-Akt leading to a reduction in contractile myocardial dysfunction.

  16. Preoperative fasting protects against renal ischemia-reperfusion injury in aged and overweight mice

    NARCIS (Netherlands)

    Jongbloed, Franny; De Bruin, Ron W F; Pennings, Jeroen L A; Payán-Gómez, César; Van Den Engel, Sandra; Van Oostrom, Conny T.; De Bruin, Alain; Hoeijmakers, Jan H J; Van Steeg, Harry; IJzermans, Jan N M; Dollé, Martijn E T

    2014-01-01

    Ischemia-reperfusion injury (IRI) is inevitable during kidney transplantation leading to oxidative stress and inflammation. We previously reported that preoperative fasting in young-lean male mice protects against IRI. Since patients are generally of older age with morbidities possibly leading to a

  17. Preoperative fasting protects against renal ischemia-reperfusion injury in aged and overweight mice

    NARCIS (Netherlands)

    F. Jongbloed (Franny); R.W.F. de Bruin (Ron); J.L.A. Pennings (Jeroen); C. Payan-Gomez; S. van den Engel (Sandra); C.T.M. van Oostrom (Conny); A. de Bruin (Alain); J.H.J. Hoeijmakers (Jan); H. van Steeg (Harry); J.N.M. IJzermans (Jan); M.E.T. Dollé (Martijn)

    2014-01-01

    textabstractIschemia-reperfusion injury (IRI) is inevitable during kidney transplantation leading to oxidative stress and inflammation. We previously reported that preoperative fasting in young-lean male mice protects against IRI. Since patients are generally of older age with morbidities possibly

  18. Preoperative fasting protects against renal ischemia-reperfusion injury in aged and overweight mice

    NARCIS (Netherlands)

    Jongbloed, Franny; De Bruin, Ron W F; Pennings, Jeroen L A; Payán-Gómez, César; Van Den Engel, Sandra; Van Oostrom, Conny T.; De Bruin, Alain; Hoeijmakers, Jan H J; Van Steeg, Harry; IJzermans, Jan N M; Dollé, Martijn E T

    2014-01-01

    Ischemia-reperfusion injury (IRI) is inevitable during kidney transplantation leading to oxidative stress and inflammation. We previously reported that preoperative fasting in young-lean male mice protects against IRI. Since patients are generally of older age with morbidities possibly leading to a

  19. Preoperative fasting protects against renal ischemia-reperfusion injury in aged and overweight mice

    NARCIS (Netherlands)

    F. Jongbloed (Franny); R.W.F. de Bruin (Ron); J.L.A. Pennings (Jeroen); C. Payan-Gomez; S. van den Engel (Sandra); C.T.M. van Oostrom (Conny); A. de Bruin (Alain); J.H.J. Hoeijmakers (Jan); H. van Steeg (Harry); J.N.M. IJzermans (Jan); M.E.T. Dollé (Martijn)

    2014-01-01

    textabstractIschemia-reperfusion injury (IRI) is inevitable during kidney transplantation leading to oxidative stress and inflammation. We previously reported that preoperative fasting in young-lean male mice protects against IRI. Since patients are generally of older age with morbidities possibly l

  20. Efeito do óleo de copaíba nas aminotransferases de ratos submetidos à isquemia e reperfusão hepática com e sem pré-condicionamento isquêmico Copaiba oil effect in rats aminotrasnferases submitted to hepatic ischemic and reperfusion with and without preconditioning

    Directory of Open Access Journals (Sweden)

    Francisco Alves de Araújo Júnior

    2005-02-01

    Full Text Available OBJETIVO: Estudar o efeito do óleo de copaíba nas aminotransferases de ratos submetidos à isquemia e reperfusão (IR hepática, com e sem pré-condicionamento isquêmico (PCI. MÉTODOS: Foram utilizados 24 Rattus norvegicus albinus machos distribuídos em: Grupo padrão (GP, Grupo copaíba (GC, Grupo isquemia-reperfusão (GIR, Grupo isquemia-reperfusão + copaíba (GIRC, Grupo pré-condicionamento isquêmico (GPCI e Grupo pré-condicionamento isquêmico + copaíba (GPCIC. Foi administrado 0,63ml/kg/dia de copaíba, durante sete dias, por meio de gavagem nos animais do GC, GIRC e GPCIC. A isquemia hepática foi de 30 minutos e, nos animais submetidos ao PCI, realizou-se isquemia de 10 minutos, seguida de reperfusão de 5 minutos e isquemia de 30 minutos com posterior reperfusão. Os animais foram anestesiados via inalatória com éter etílico. O período de reperfusão foi de 24 horas. No 1° DPO foi realizada coleta de sangue venoso e dosagem das aminotransferases. RESULTADOS: Os níveis de AST não se alteraram nos animais submetidos à administração do óleo de copaíba. O óleo estudado não alterou os valores de ALT no GIRC quando comparado com o GIR, entretanto, houve aumento do nível sérico dessa enzima no GPCIC em comparação com o GPCI. CONCLUSÃO: O óleo de copaíba não alterou os níveis de AST nos grupos estudados. Ao se avaliar a ALT, esse óleo não influenciou os valores séricos nos animais submetidos somente à IR hepática, entretanto houve aumento dos níveis dessa enzima no GPCIC em relação ao seu controle. Os valores de ALT não foram diferentes estatisticamente entre os grupos IRC e PCIC.PURPOSE: To study the copaiba oil effect in rats' aminotrasnferases submited to hepatic ischemic and reperfusion with and without preconditioning. METHODS: 24 male and adults rats (Rattus norvegicus albinus,Wistar were distributed into six groups: Standard Group (SG; Copaiba Group (CG, Ischemic-reperfusion Group (IRG, Ischemic-reperfusion

  1. Hypoxia inducible factor 1-alpha (HIF-1 alpha is induced during reperfusion after renal ischemia and is critical for proximal tubule cell survival.

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    Elisa Conde

    Full Text Available Acute tubular necrosis (ATN caused by ischemia/reperfusion (I/R during renal transplantation delays allograft function. Identification of factors that mediate protection and/or epithelium recovery could help to improve graft outcome. We studied the expression, regulation and role of hypoxia inducible factor 1-alpha (HIF-1 α, using in vitro and in vivo experimental models of I/R as well as human post-transplant renal biopsies. We found that HIF-1 α is stabilized in proximal tubule cells during ischemia and unexpectedly in late reperfusion, when oxygen tension is normal. Both inductions lead to gene expression in vitro and in vivo. In vitro interference of HIF-1 α promoted cell death and in vivo interference exacerbated tissue damage and renal dysfunction. In pos-transplant human biopsies, HIF-1 α was expressed only in proximal tubules which exhibited normal renal structure with a significant negative correlation with ATN grade. In summary, using experimental models and human biopsies, we identified a novel HIF-1 α induction during reperfusion with a potential critical role in renal transplant.

  2. Postconditioning with cyclosporine a reduces early renal dysfunction by inhibiting mitochondrial permeability transition.

    Science.gov (United States)

    Lemoine, Sandrine; Pillot, Bruno; Rognant, Nicolas; Augeul, Lionel; Rayberin, Maud; Varennes, Annie; Laville, Maurice; Ovize, Michel; Juillard, Laurent

    2015-04-01

    Ischemia-reperfusion (IR) injury leads to mitochondrial permeability transition pore opening, which contributes to cell death. The aim of this study is to determine whether ischemic or pharmacological postconditioning with cyclosporine A (CsA) might protect the kidney from lethal reperfusion injury. Male mice underwent a unilateral (right) nephrectomy followed by 30 minutes of contralateral (left) clamping of the renal artery. We studied 4 groups at 20 minutes and 24 hours of reperfusion: a sham group (n = 4), an ischemic group (n = 6), CsA-postconditioned group (postcond-CsA, injection of 3 mg/kg of CsA 5 minutes before the end of ischemia, (n = 6), and an ischemic postconditioning (IPC) group (n = 6), consisting of 3 cycles of 30 seconds of renal ischemia with 30 seconds intervening reperfusion. After 24 hours of reperfusion, we measured plasma creatinine, urea, and histological kidney injury. The kidney mitochondria were isolated to assess the mitochondria calcium retention capacity and oxidative phosphorylation. At 24 hours after reperfusion, serum creatinine decreased in postcond-CsA and IPC compared to ischemic group. The histological score was also significantly improved with postcond-CsA and IPC. At 20 minutes and 24 hours of reperfusion, calcium retention capacity was decreased significantly in the ischemic group. The mitochondrial respiration stay decreased in the ischemic group at 24 hours of reperfusion, whereas the respiration was improved significantly in the postcond-CsA and IPC group. Bax and cleaved caspase 3 decreased in PostCsA and IPC group. Our results suggest that IPC and CsA, administered immediately before reperfusion, protect the kidney from lethal injury.

  3. Amniotic Fluid Derived Stem Cells with a Renal Progenitor Phenotype Inhibit Interstitial Fibrosis in Renal Ischemia and Reperfusion Injury in Rats.

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    Marina Gabriela Monteiro Carvalho Mori da Cunha

    Full Text Available Mesenchymal stem cells derived from human amniotic fluid (hAFSCs are a promising source for cellular therapy, especially for renal disorders, as a subpopulation is derived from the fetal urinary tract. The purpose of this study was to evaluate if hAFSCs with a renal progenitor phenotype demonstrate a nephroprotective effect in acute ischemia reperfusion (I/R model and prevent late stage fibrosis.A total of 45 male 12-wk-old Wistar rats were divided into three equal groups;: rats subjected to I/R injury and treated with Chang Medium, rats subjected to I/R injury and treated with hAFSCs and sham-operated animals. In the first part of this study, hAFSCs that highly expressed CD24, CD117, SIX2 and PAX2 were isolated and characterized. In the second part, renal I/R injury was induced in male rats and cellular treatment was performed 6 hours later via arterial injection. Functional and histological analyses were performed 24 hours, 48 hours and 2 months after treatment using serum creatinine, urine protein to creatinine ratio, inflammatory and regeneration markers and histomorphometric analysis of the kidney. Statistical analysis was performed by analysis of variance followed by the Tukey's test for multiple comparisons or by nonparametric Kruskal-Wallis followed by Dunn. Statistical significance level was defined as p <0.05.hAFSCs treatment resulted in significantly reduced serum creatinine level at 24 hours, less tubular necrosis, less hyaline cast formation, higher proliferation index, less inflammatory cell infiltration and less myofibroblasts at 48 h. The treated group had less fibrosis and proteinuria at 2 months after injury.hAFSCs contain a renal progenitor cell subpopulation that has a nephroprotective effect when delivered intra-arterially in rats with renal I/R injury, and reduces interstitial fibrosis on long term follow-up.

  4. Effect of remote ischemic postconditioning in inflammatory changes of the lung parenchyma of rats submitted to ischemia and reperfusion

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    Rafael Cantero Dorsa

    2015-09-01

    Full Text Available AbstractObjective:To assess the effects of postconditioning remote in ischemia-reperfusion injury in rat lungs.Methods:Wistar rats (n=24 divided into 3 groups: GA (I/R n=8, GB (R-Po n=8, CG (control n=8, underwent ischemia for 30 minutes artery occlusion abdominal aorta, followed by reperfusion for 60 minutes. Resected lungs and performed histological analysis and classification of morphological findings in accordance with the degree of tissue injury. Statistical analysis of the mean rating of the degree of tissue injury.Results:GA (3.6, GB (1.3 and CG (1.0. (GA GB X P<0.05.Conclusion:The remote postconditioning was able to minimize the inflammatory lesion of the lung parenchyma of rats undergoing ischemia and reperfusion process.

  5. Role of Centella asiatica on cerebral post-ischemic reperfusion and long-term hypoperfusion in rats

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    Raghavendra M

    2009-01-01

    Full Text Available Centella asiatica (CA, a well known adaptogenic agent in Indian system of Medicine (Ayurveda, is believed to have beneficial effects in improving memory, treating anxiety and eczema. It also possesses antioxidant, cognitive enhancing and antiepileptic properties. Acute ischemia followed by reperfusion is known to bring about biochemical and histopathological alterations. In the present study the effect of Centella asiatica on acute cerebral reperfusion and long-term cerebral hypoperfusion in rats was investigated. Transient cerebral ischemia was induced under Ketamine anaesthesia by blocking bilateral common carotid arteries (BCCAO for 30 min and then reperfusion was allowed for 45 min by releasing the block. Lipid peroxidation, superoxide dismutase (SOD and brain protein were estimated, behavioral and histopathological studies were done for both acute ischemia-reperfusion and chronic hypoperfusion studies. One way ANOVA followed by post hoc Tukey test was used. In the present study, acute ischemia-reperfusion induced increases in lipid peroxidation and superoxide SOD activity. CA pre-treatment (100 mg/kg p.o. for 5 days attenuated the reperfusion induced biochemical alterations. Long-term cerebral hypoperfusion in rats caused a propensity towards anxiety and listlessness (open field paradigm and elevated plus maze test accompanied by deficits in learning and memory (Morris′ water maze testing and tendency towards depression (Porsolts swim test. Additionally, histopathological observations in forebrain revealed changes like gliosis, astrocytosis, cellular edema and inflammatory changes. CA treatment (100 mg/kg p.o. for 28 days alleviated these behavioral, cognitive and histopathological changes. The results suggest that CA may be useful in cerebrovascular insufficiency conditions.

  6. Liver Ameliorative Effects of the Hydroalcohol Extract of Rosa canina L. Fruit against Ischemic Acute Renal Failure-induced Hepatic Damage in Wistar Rats

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    F. Gholampour

    2013-01-01

    Full Text Available Recent studies have shown remote effects of renal Ischemia/Reperfusion (I/R injury on the liver. Furthermore, I/R injury is correlated with the generation of Reactive Oxygen Species (ROS. This study investigated the effect of Rosa canina on the hepatic dysfunction and histological damage induced by renal ischaemia/ reperfusion at an early stage. There were three groups (n = 10, in which rats received orally 7 days before induction of ischemia, extract of Rosa canina (500 mg kg-1 in RC+I/R group and distilled water in I/R group. In sham group, the renal arteries were not occluded and distilled water was administered orally 7 days before surgery. Renal ischemia was induced by both renal arteries occlusion for 45 min followed by 24 h of reperfusion. Blood samples were collected for biochemical analysis and finally liver samples were preserved for future histological examination. The renal ischaemic challenge resulted in major histological damages of the liver (pRosa canina exhibited a hepatoameliorative effect against renal ischemia/reperfusion-induced lesions.

  7. Prevalence, correlative and statistical relationships of renal dysfunction in patients with chronic ischemic heart failure

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    D. A. Lashkul

    2014-02-01

    Full Text Available Chronic heart failure (CHF is one of the most common complications of cardiovascular disease. According multicenter studies conducted during recent years, coronary heart disease was the leading cause of heart failure and has been on average 64% of patients with chronic heart failure. The tight functional relationship of cardiovascular and urinary system causes a lot of interest to the functional state of kidneys in various cardiovascular diseases. Most risk factors for cardiovascular disease are common risk factors of renal failure. Causes significant differences in the prevalence of chronic kidney disease (CKD in patients with chronic heart failure, defined as coronary artery disease and hypertension remain unclear. Need clarification prevalence of CKD among patients with CHF in general and in specific groups of patients. The aim of the study was to examine the prevalence, correlation and statistical relationships of renal dysfunction with functional class, age and gender of patients with coronary heart disease and heart failure, were hospitalized. Materials and methods. Analyzed the medical cards 344 patients (286 men and 58 women with ischemic chronic heart failure, mean age 59.2±9.4 years. The etiology of heart failure in 298 (86.6% patients had a combination of coronary artery disease and essential hypertension in 46 (13.4% - CHD. Chronic heart failure 1 functional class (FC was diagnosed in 10 (2.9% patients, 2 FC - in 106 (31%, 3 FC - 207 (60.5% and 4 FC - 19 (5, 6% patients. Diabetes was 62 (18% patients. Myocardial infarction had a history of 245 (71.2% patients. Glomerular filtration rate was calculated using the formula MDRD (Modification of Diet in Renal Disease. Descriptive statistics are presented as mean±standard deviation for continuous variables and as percentages for categorical variables. Depending on the distribution of the analyzed parameters used unpaired Student's t-test or U-Mann-Whitney test. Comparisons among all

  8. Beneficial effect of medicinal plants on the contractility of post-hypoxic isolated guinea pig atria - Potential implications for the treatment of ischemic-reperfusion injury.

    Science.gov (United States)

    Bipat, Robbert; Toelsie, Jerry R; Magali, Indira; Soekhoe, Rubaina; Stender, Karin; Wangsawirana, Angelique; Oedairadjsingh, Krishan; Pawirodihardjo, Jennifer; Mans, Dennis R A

    2016-08-01

    Context Ischemic-reperfusion injury is accompanied by a decreased contractility of the myocardium. Positive-inotropic agents have proven useful for treating this condition but may exert serious side-effects. Objective In this study, aqueous preparations from Abelmoschus esculentus L. Moench (Malvaceae), Annona muricata L. (Annonaceae), Bixa orellana L. (Bixaceae), Cecropia peltata L. (Moraceae), Erythrina fusca Lour. (Fabaceae), Psidium guajava L. (Myrtaceae) and Terminalia catappa L. (Combretaceae) were evaluated for their ability to improve the decreased contractility of isolated guinea pig atria after hypoxic stress. Materials and methods Guinea pig atria isolated in Ringer-Locke buffer gassed with 100% O2 at 30 °C were exposed for 5 min to hypoxia, then allowed to recover in oxygenated buffer alone or containing a single plant extract (0.001-1 mg/mL). The contractility (g/s) and beating frequency (beats/min), as well as troponin C contents of the bathing solution (ng/mL), were determined and expressed as means ± SDs. Results The extracts of A. muricata, B. orellana, C. peltata and T. catappa caused an increase in the contractility compared to untreated atria of 340 ± 102%, 151 ± 13%, 141 ± 14% and 238 ± 44%, respectively. However, the latter two preparations increased the troponin C contents of the bathing solution to 36 ± 11 and 69 ± 33, compared to the value of 11 ± 3 ng/mL found with untreated atria. Conclusions Preparations from A. muricata and B. orellana may possess positive-inotropic properties which may improve the contractility of the post-hypoxic myocardium. Studies to assess their usefulness in ischemic-reperfusion injury are warranted.

  9. DPP-4 Inhibitor and Estrogen Share Similar Efficacy Against Cardiac Ischemic-Reperfusion Injury in Obese-Insulin Resistant and Estrogen-Deprived Female Rats

    Science.gov (United States)

    Sivasinprasasn, Sivaporn; Tanajak, Pongpan; Pongkan, Wanpitak; Pratchayasakul, Wasana; Chattipakorn, Siriporn C.; Chattipakorn, Nipon

    2017-01-01

    Estrogen deprivation aggravates cardiac injury after myocardial ischemia and reperfusion (I/R) injury. Although either estrogen or the dipeptidyl peptidase-4 (DPP-4) inhibitor, vildagliptin, reduces myocardial damage following cardiac I/R, their effects on the heart in obese-insulin resistant and estrogen deprived conditions remain unknown. Ovariectomized (O) rats (n = 36) were divided to receive either normal diet (NDO) or high-fat diet (HFO) for 12 weeks, followed by treatment with a vehicle, estrogen or vildagliptin for 4 weeks. The setting of in vivo cardiac I/R injury, 30-min ischemia and 120-min reperfusion, was performed. At 12 weeks after ovariectomy, both NDO and HFO rats exhibited an obese-insulin resistant condition. Both NDO and HFO rats treated with estrogen and vildagliptin showed reduced fasting plasma glucose, insulin and HOMA index. Both treatments improved cardiac function indicated by restoration of heart rate variability and increased %left ventricular ejection fraction (%LVEF). The treatments similarly protected cardiac mitochondrial function against I/R injury, leading to a reduction in the infarct size, oxidative stress and apoptosis in the ischemic myocardium. These findings demonstrate that vildagliptin effectively improves metabolic status, and shares similar efficacy to estrogen in reducing myocardial infarction and protecting cardiac mitochondrial function against I/R injury in estrogen-deprived obese-insulin resistant rats. PMID:28281660

  10. 气体信号分子硫化氢与缺血再灌注损伤%Gasotransmitter hydrogen sulfide and ischemic reperfusion

    Institute of Scientific and Technical Information of China (English)

    王新宝

    2012-01-01

    Recently hydrogen sulfide ( H2S) is considered the third gasotransmitter and exerts important biological effects in mammals. Studies found that H2S could reduce ischemia reperfusion injury in heart, lung, liver, kidney and intestine. The mechanisms were related to opening of ATP sensitive kalium channel, reducing free radical formation, and inhibiting cell apoptosis and inflammation. The present article reviewed the effect and mechanisms of H2 S on ischemic reperfusion.%气体分子硫化氢(H2S)是近年来发现的第3种气体信号分子,在机体中发挥着重要的生物学作用,H2S可以明显减轻心脏、肺、肝脏、肾脏和小肠的缺血再灌注损伤,其机制与开放ATP敏感性钾、减少自由基的生成,抑制细胞凋亡和炎性反应有关,本文就H2S对缺血再灌注的作用及机制进行了综述

  11. Evidence of a Heterogeneous Tissue Oxygenation: Renal Ischemia/Reperfusion Injury in a Large Animal Model

    Science.gov (United States)

    2013-03-01

    Department of Surgery, 8901 Wisconsin Avenue, Bethesda, Maryland 20814 eNational Institutes of Diabetes and Digestive and Kidney Diseases, Laboratory of...oxy-hemoglobin concen- trations calculated for the entire kidney [Fig. 5(a)] and each kid - ney segment [Fig. 5(b)] and is representative of all...healthy kid - neys with good baseline glomerular filtration rates (GFRs), these events can often be reversed after a period of reperfusion (either in

  12. The Effects of Different Repetitive Transcranial Magnetic Stimulation (rTMS) Protocols on Cortical Gene Expression in a Rat Model of Cerebral Ischemic-Reperfusion Injury.

    Science.gov (United States)

    Ljubisavljevic, Milos R; Javid, Asma; Oommen, Joji; Parekh, Khatija; Nagelkerke, Nico; Shehab, Safa; Adrian, Thomas E

    2015-01-01

    Although repetitive Transcranial Magnetic Stimulation (rTMS) in treatment of stroke in humans has been explored over the past decade the data remain controversial in terms of optimal stimulation parameters and the mechanisms of rTMS long-term effects. This study aimed to explore the potential of different rTMS protocols to induce changes in gene expression in rat cortices after acute ischemic-reperfusion brain injury. The stroke was induced by middle cerebral artery occlusion (MCAO) with subsequent reperfusion. Changes in the expression of 96 genes were examined using low-density expression arrays after MCAO alone and after MCAO combined with 1Hz, 5Hz, continuous (cTBS) and intermittent (iTBS) theta-burst rTMS. rTMS over the lesioned hemisphere was given for two weeks (with a 2-day pause) in a single daily session and a total of 2400 pulses. MCAO alone induced significant upregulation in the expression of 44 genes and downregulation in 10. Two weeks of iTBS induced significant increase in the expression of 52 genes. There were no downregulated genes. 1Hz and 5Hz had no significant effects on gene expression, while cTBS effects were negligible. Upregulated genes included those involved in angiogenesis, inflammation, injury response and cellular repair, structural remodeling, neuroprotection, neurotransmission and neuronal plasticity. The results show that long-term rTMS in acute ischemic-reperfusion brain injury induces complex changes in gene expression that span multiple pathways, which generally promote the recovery. They also demonstrate that induced changes primarily depend on the rTMS frequency (1Hz and 5Hz vs. iTBS) and pattern (cTBS vs. iTBS). The results further underlines the premise that one of the benefits of rTMS application in stroke may be to prime the brain, enhancing its potential to cope with the injury and to rewire. This could further augment its potential to favorably respond to rehabilitation, and to restore some of the loss functions.

  13. The Effects of Different Repetitive Transcranial Magnetic Stimulation (rTMS Protocols on Cortical Gene Expression in a Rat Model of Cerebral Ischemic-Reperfusion Injury.

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    Milos R Ljubisavljevic

    Full Text Available Although repetitive Transcranial Magnetic Stimulation (rTMS in treatment of stroke in humans has been explored over the past decade the data remain controversial in terms of optimal stimulation parameters and the mechanisms of rTMS long-term effects. This study aimed to explore the potential of different rTMS protocols to induce changes in gene expression in rat cortices after acute ischemic-reperfusion brain injury. The stroke was induced by middle cerebral artery occlusion (MCAO with subsequent reperfusion. Changes in the expression of 96 genes were examined using low-density expression arrays after MCAO alone and after MCAO combined with 1Hz, 5Hz, continuous (cTBS and intermittent (iTBS theta-burst rTMS. rTMS over the lesioned hemisphere was given for two weeks (with a 2-day pause in a single daily session and a total of 2400 pulses. MCAO alone induced significant upregulation in the expression of 44 genes and downregulation in 10. Two weeks of iTBS induced significant increase in the expression of 52 genes. There were no downregulated genes. 1Hz and 5Hz had no significant effects on gene expression, while cTBS effects were negligible. Upregulated genes included those involved in angiogenesis, inflammation, injury response and cellular repair, structural remodeling, neuroprotection, neurotransmission and neuronal plasticity. The results show that long-term rTMS in acute ischemic-reperfusion brain injury induces complex changes in gene expression that span multiple pathways, which generally promote the recovery. They also demonstrate that induced changes primarily depend on the rTMS frequency (1Hz and 5Hz vs. iTBS and pattern (cTBS vs. iTBS. The results further underlines the premise that one of the benefits of rTMS application in stroke may be to prime the brain, enhancing its potential to cope with the injury and to rewire. This could further augment its potential to favorably respond to rehabilitation, and to restore some of the loss

  14. Effects of Rosa Canina L. on Ischemia/ Reperfusion Injury in Anesthetized Rats

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    S Karimi

    2012-04-01

    Full Text Available Background: Ischemia/reperfusion induced acute renal failure causes excretory functional disorders of nephrons. Ischemia/reperfusion injury is accompanied by generation of reactive oxygen species that leads to dysfunction, injury, and death of renal cells. Antioxidants of plant origin minimize the harmful effects of reactive oxygen species. The aim of this study was to determine the possible therapeutic potentials of Rosa canina L. in preventing renal functional disturbances during the post-ischemic reperfusion period. Methods: In this experimental study undertaken for evaluating renal excretory function in 30 male Wistar rats, renal ischemia was induced by occluding both renal arteries for 45 min, followed by 24 h of reperfusion. The rats received 2 ml of tap water or a hydroalcoholic extract of Rosa canina (500 mg/kg orally for 7 days before induction of ischemia. In plasma samples, creatinine and urea nitrogen levels were measured, and in renal tissue samples, red blood cells were counted. The data were analyzed using ANOVA and Duncan tests.Results: Renal ischemia for 45 minutes increased plasma levels of creatinine (P<0.001 and nitrogen urea (P<0.01 while reducing red blood cell counts in renal glomeruli (P<0.001. Rosa canina administration diminished the increase in creatinine (P<0.001 and nitrogen urea concentrations (P<0.01, and prevented reductions in red blood cell counts in renal glomeruli (P<0.001. Conclusion: Rosa canina seems to be useful as a preventive agent against renal damages induced by ischemia/reperfusion injuries in rats.

  15. Polydatin ameliorates renal ischemia/reperfusion injury by decreasing apoptosis and oxidative stress through activating sonic hedgehog signaling pathway.

    Science.gov (United States)

    Meng, Qiu-Hong; Liu, Hong-Bao; Wang, Jian-Bo

    2016-10-01

    Polydatin, a glucoside of resveratrol, recently has been demonstrated possibly to exert its biological effects by targeting sonic hedgehog (Shh). However, whether Shh signaling pathway is involved in the therapeutic effects of polydatin for renal ischemia/reperfusion (I/R) injury has not been evaluated. Our results showed that I/R induced the secretion of Shh, upregulated Patched and Smoothened, and enhanced the nuclear translocation and target gene transcription of Glioblastoma 1 in renal I/R injury models, which were further upregulated after the administration of polydatin significantly and in turn exerted prominent nephroprotective effects against cell apoptosis and oxidative stress. The treatment with cyclopamine (a specific inhibitor of Smoothened) or 5E1 (an anti-Shh antibody) not only markedly inhibited the activation of the Shh pathway, but also dramatically suppressed the nephroprotective effects of polydatin above-mentioned. These results advance our knowledge that polydatin can provide protection for kidneys against I/R injury by enhancing antioxidant capacity and decreasing cell apoptosis through activating Shh signaling pathway.

  16. Protective effect of moxonidine on ischemia/reperfusion-induced acute kidney injury through α2/imidazoline I1 receptor.

    Science.gov (United States)

    Tsutsui, Hidenobu; Sugiura, Takahiro; Hayashi, Kentaro; Yukimura, Tokihito; Ohkita, Mamoru; Takaoka, Masanori; Matsumura, Yasuo

    2013-10-15

    Enhancement of renal sympathetic nerve activity during renal ischemia and norepinephrine overflow from the kidney after reperfusion play important roles in the development of ischemic acute kidney injury. Recently, we have found that moxonidine, an α2/imidazoline Ι1-receptor agonist, has preventive effects on ischemic acute kidney injury by suppressing the excitation of renal sympathetic nervous system after reperfusion. In the present study, to clarify the renoprotective mechanisms of moxonidine (360 nmol/kg, i.v.) against ischemic acute kidney injury, we investigated the effect of intravenous (i.v.) and intracerebroventricular (i.c.v.) injection of efaroxan, an α2/Ι1 receptor antagonist, on the moxonidine-exhibited actions. Ischemic acute kidney injury was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. The suppressive effect of moxonidine on enhanced renal sympathetic nerve activity during renal ischemia was not observed in the rat treated with either i.v. (360 nmol/kg) or i.c.v. (36 nmol/kg) of efaroxan. Furthermore, i.v. injection of efaroxan eliminated the preventive effect of moxonidine on ischemia/reperfusion-induced kidney injury and norepinephrine overflow, and i.c.v. injection of efaroxan did not completely inhibit the moxonidine's effects. These results indicate that moxonidine prevents the ischemic kidney injury by sympathoinhibitory effect probably via α2/Ι1 receptors in central nervous system and by suppressing the norepinephrine overflow through α2/Ι1 receptors on sympathetic nerve endings.

  17. Topical hepatic hypothermia plus ischemic preconditioning: analysis of bile flow and ischemic injuries after initial reperfusion in rats Hipotermia hepática tópica mais pré-condicionamento isquêmico: análise do fluxo biliar e danos isquêmicos após a reperfusão inicial em ratos

    Directory of Open Access Journals (Sweden)

    Tomaz de Jesus Maria Grezzana Filho

    2011-06-01

    Full Text Available PURPOSE: To evaluate the effects of the topical liver hypothermia and IPC combination against I/R injury after initial reperfusion. METHODS: In 32 Wistar rats, partial liver ischemia was induced for 90 minutes in normothermia (IN, ischemic preconditioning (IPC, 26ºC topical hypothermia (H and 26ºC topical hypothermia plus IPC (H+IPC. MAP, body temperature and bile flow were recorded each 15 minutes. Plasmatic injury markers and tissue antioxidant defenses were assessed after 120 minutes of reperfusion. RESULTS: MAP and body temperature remained constant during all experiment. Bile flow returned to levels similar to controls after 45 minutes of reperfusion in the H and H+IPC groups and increased significantly in comparison to the NI and IPC groups after 105 and 120 minutes. AST and ALT increased significantly in the normothermic groups in comparison to controls. TBARS levels decreased significantly in the H+IPC group in comparison to the other groups whereas Catalase levels increased significantly in the IPC group. SOD levels were significantly higher in the H group in comparison to all groups. CONCLUSION: The induction of 26ºC topical hypothermia associated or not to IPC protected the ischemic liver against ischemia/reperfusion injuries and allowed an early recovery of the hepatic function.OBJETIVO: Avaliar os efeitos da hipotermia hepática tópica combinada ao pré-condicionamento isquêmico na proteção dos danos iniciais de isquemia e reperfusão. MÉTODOS: Trinta e dois ratos Wistar foram submetidos à isquemia hepática parcial durante 90 minutos em Normotermia (IN, Pré-condicionamento Isquêmico (IPC, Hipotermia a 26ºC (H e Hipotermia a 26ºC mais PCI (H+PCI. A PAM, a temperatura corporal e o fluxo biliar foram aferidos em intervalos de 15 minutos. Marcadores plasmáticos de danos hepáticos e as defesas antioxidantes foram avaliados após 120 minutos de reperfusão. RESULTADOS: A PAM e a temperatura corporal permaneceram constantes

  18. Effects of combined ischemic postconditioning, remote ischemic postconditioning and naloxone postconditioning on focal cerebral ischemia-reperfusion injury in rats%联合应用缺血后处理、远隔缺血后处理和纳洛酮后处理对大鼠脑缺血-再灌注损伤的影响

    Institute of Scientific and Technical Information of China (English)

    刘毅; 廖旭; 薛富善; 许亚超; 熊军; 袁玉静; 王强; 刘建华; 赵嘉训

    2011-01-01

    Objective To assess the effects of ischemic postconditioning, remote ischemic postconditioning and naloxone postconditioning on focal cerebral ischemia-reperfusion injury in rats.Methods A total of 110 adult SD rats were randomly divided into 5 groups (n =22 each). The focal cerebral ischemia-reperfusion injury was induced by a 90-minute occlusion of right middle cerebral artery (MCA) and a 24-hour reperfusion sequentially. Group 1 was of ischemia-reperfusion control; Group 2 ischemic postconditioning induced by three 30-second cycles of MCA occlusion followed by a 30-second reperfusion; Group 3 remote ischemic postconditioning performed via a transient occlusion of right femoralartery at 5 min before the initiatlon of reperfusion:Group 4 naloxone posteonditioning with naloxone 10 mg/kg intraperitoneaUy injected at the initiation of reperfusion;Group 5 combined ischemic,remote ischernic & naloxone postconditioning performed simultaneously in accordance with the methods used in Groups 2,3 & 4.The neumlogie deftcit scores(NDS)were obtained at 2 h & 24 h post-reperfusion.At 24 h post-reperfusion.the anesthetized rat was sacrificed by decapitation and the brain rapidly extracted to asseSS the size ofcerebral infaret(n=10),detect the cerebral expression of microtubule-associated protein2(MAP2)(n=6),measure the plasma volume of cerebral tissues and quantify the diameter and segment artery at 5 min before the initiation of reperfusion; Group 4 naloxone postconditioning with naloxone 10 mg/kg intraperitoneally injected at the initiation of reperfusion; Group 5 combined ischemic, remote ischemic & naloxone postconditioning performed simultaneously in accordance with the methods used in Groups 2, 3 & 4. The neurologic deficit scores ( NDS) were obtained at 2 h & 24 h post-reperfusion. At 24 h post-reperfusion, the anesthetized rat was sacrificed by decapitation and the brain rapidly extracted to assess the size of cerebral infarct (n = 10), detect the cerebral expression of

  19. Sulforaphane improves outcomes and slows cerebral ischemic/reperfusion injury via inhibition of NLRP3 inflammasome activation in rats.

    Science.gov (United States)

    Yu, Chang; He, Qi; Zheng, Jing; Li, Ling Yu; Hou, Yang Hao; Song, Fang Zhou

    2017-04-01

    Ischemia/reperfusion (I/R) injury has been correlated with systemic inflammatory response. In addition, NLRP3 has been suggested as a cause in many inflammatory processes. Sulforaphane (SFN) is a naturally occurring isothiocyanate found in cruciferous vegetables, such as broccoli and cabbage. While recent studies have demonstrated that Sulforaphane has protective effects against cerebral ischemia/reperfusion injury, little is known about how those protective effects work. In this study, we focus our investigation on the role and process of Sulforaphane in the inhibition of NLRP3 inflammasome activation, as well as its effect on brain ischemia/reperfusion injury. Adult male Sprague-Dawley rats were injected with Sulforaphane (5 or 10mg/kg) intraperitoneally at the beginning of reperfusion, after a 60min period of occlusion. A neurological score and infarct volume were assessed at 24h after the administration of Sulforaphane. Myeloperoxidase (MPO) activity was measured at 24h to assess neutrophil infiltration in brain tissue. ELISA, RT-PCR and Western blot analyses were used to measure any inflammatory reaction. Sulforaphane treatment significantly reduced infarct volume and improved neurological scores when compared to a vehicle-treated group. Neutrophil infiltration was significantly higher in the vehicle-treated group than in the Sulforaphane treatment group. Sulforaphane treatment inhibits NLRP3 inflammasome activation and the downregulation of cleaved caspase-1, while reducing IL-1β and IL-18 expression. The inhibition of inflammatory response with Sulforaphane treatment improves outcomes after focal cerebral ischemia. This neuroprotective effect is likely exerted by Sulforaphane inhibited NLRP3 inflammasome activation caused by the downregulation of NLRP3, the induction of cleaved caspase-1, and thus the reduction of IL-1β and IL-18. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Metabolism of eicosanoids and their action on renal function during ischaemia and reperfusion: the effect of alprostadil.

    Science.gov (United States)

    Dołegowska, B; Pikuła, E; Safranow, K; Olszewska, M; Jakubowska, K; Chlubek, D; Gutowski, P

    2006-12-01

    Eicosanoids, active metabolites of arachidonic acid (AA), play an important role in the regulation of renal haemodynamics and glomerular filtration. Our study verified the hypothesis on the positive action of exogenously administered PGE(1) on renal function during an operation with temporary ischaemia of the lower half of the body. Also the effect of alprostadil (prostaglandin E(1) analogue) administered during the operation of an abdominal aorta aneurysm on the postoperative systemic metabolism of AA and the glomerular filtration rate (GFR) was investigated. The study included 42 patients with a diagnosed abdominal aorta aneurysm who have been qualified for the operation of implantation of the aortic prosthesis. The patients were randomly assigned to two groups: the study group (I) receiving alprostadil and the control group (II) without alprostadil. The levels of hydroxyeicosatetraenoic acids (15-HETE, 12-HETE, 5-HETE) were determined by RP-HPLC and the level of thromboxane B(2) (TxB(2)) was determined by ELISA in the plasma of the blood drawn from vena cava superior immediately before aortic clamping (A) and 5 min after aortic declamping (B). The administration of PGE(1) affects the metabolism of 15-HETE in a manner dependent on the baseline value of GFR but does not significantly change the postoperative renal function. The metabolism of 15-HETE is affected by the baseline value of GFR1 and a longer period of ischaemia is correlated with lower concentrations of 5-HETE during reperfusion. The results of our studies indicate that TxB(2) influences the postoperative function of kidneys.

  1. Achyranthes bidentata Polypeptides Reduces Oxidative Stress and Exerts Protective Effects against Myocardial Ischemic/Reperfusion Injury in Rats

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    Haifeng Zhang

    2013-09-01

    Full Text Available Achyranthes bidentata, a Chinese medicinal herb, is reported to be neuroprotective. However, its role in cardioprotection remains largely unknown. Our present study aimed to investigate the effects of Achyranthes bidentata polypeptides (ABPP preconditioning on myocardial ischemia/reperfusion (MI/R injury and to test the possible mechanisms. Rats were treated with ABPP (10 mg/kg/d, i.p. or saline once daily for one week. Afterward, all the animals were subjected to 30 min of myocardial ischemia followed by 4 h of reperfusion. ABPP preconditioning for one week significantly improved cardiac function following MI/R. Meanwhile, ABPP reduced infarct size, plasma creatine kinase (CK/lactate dehydrogenase (LDH activities and myocardial apoptosis at the end of reperfusion in rat hearts. Moreover, ABPP preconditioning significantly inhibited superoxide generation, gp91phox expression, malonaldialdehyde formation and enhanced superoxide dismutase activity in I/R hearts. Furthermore, ABPP treatment inhibited PTEN expression and increased Akt phosphorylation in I/R rat heart. PI3K inhibitor wortmannin blocked Akt activation, and abolished ABPP-stimulated anti-oxidant effect and cardioprotection. Our study demonstrated for the first time that ABPP reduces oxidative stress and exerts cardioprotection against MI/R injury in rats. Inhibition of PTEN and activation of Akt may contribute to the anti-oxidant capacity and cardioprotection of ABPP.

  2. Atividade da catalase no pulmão, rim e intestino delgado não isquemiado de ratos após reperfusão intestinal Catalase activity in lung, kidney and small bowel non-ischemic in rats after intestinal reperfusion

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    Camila de Oliveira Ferro

    2010-02-01

    Full Text Available OBJETIVO: Avaliar a atividade catalase, após lesão por isquemia e reperfusão intestinal e estudar as alterações deste antioxidante em órgãos situados à distância do insulto inicial. MÉTODOS: Utilizaram-se 18 ratos do tipo Wistar, aleatoriamente distribuídos em três grupos. 1-Controle, 2-Simulação e 3-Isquemia/Reperfusão. Neste último, realizou-se isquemia no íleo, por 60 minutos, seguida de reperfusão por 30 minutos. No grupo 2 efetuou-se apenas uma laparotomia. Foram retirados, de todos os animais, segmentos do intestino com e sem reperfusão, além do pulmão e rim direitos para exame com microscopia óptica. A atividade da catalase foi aferida em espectrofotômetro ajustado para 240 nm. Utilizaram-se os testes estatísticos Mann e Whitney e Kruskal Wallis. RESULTADOS: Observou-se aumento significante (p OBJECTIVE: This study aimed to assess the catalase activity after ischemia and reperfusion and to study the changes of this antioxidant in organs located far from the initial insult. METHODS: Eighteen Wistar rats were randomly divided into three groups. 1-Control, 2-Simulation and 3-Ischemia and Reperrfusion. In the latter it was done an ischemia of the ileum for 60 minutes followed by reperfusion for 30 minutes. In group 2 only laparotomy was performed. From all animals it was taken segments of the reperfused and non reperfused intestine, as well of the right kidney and lung to be evaluated under light microscopy. Catalase activity was measured in spectrophotometer with a wavelength set to 240 nm. It was used Mann Whitney and Kruskal Wallis statistical tests. RESULTS: There was a significant increase (p <0.05 in the catalase activity not only at small bowel ischemic and non-ischemic segments but also at lungs. However the enzymatic activity decreases in the kidney. In all organs studied at reperfusion group it was found a slight villi derangement, mild congestion and infiltration with inflammatory cells, and areas of

  3. RENAL ISCHEMIA-REPERFUSION INJURY CONTRIBUTES TO RENAL DAMAGE IN EXPERIMENTAL ANTI-MYELOPEROXIDASE-ASSOCIATED PROLIFERATIVE GLOMERULONEPHRITIS

    NARCIS (Netherlands)

    BROUWER, E.; Klok, P.A; HUITEMA, M.G.; Weening, J.J.; Kallenberg, Cees

    1995-01-01

    The occurrence of focal fibrinoid necrosis of capillary loops in the very early stages of ANCA-associated necrotizing crescentic glomerulonephritis (NCGN) and the increased prevalence of this disease at older age suggest that renal ischemia may play an additional role in its pathophysiology. In the

  4. Sinvastatina e lesão renal aguda isquêmica em ratos Simvastatina y lesión renal aguda isquémica en ratas Simvastatin and acute ischemic renal injury in rats

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    Claudia Akemi Shibuya Teshima

    2012-01-01

    Full Text Available OBJETIVOS: O estudo visou verificar a ação renoprotetora da sinvastatina em modelo animal de isquemia/reperfusão por 30 minutos. MÉTODOS: A isquemia foi obtida por meio do clampeamento dos pedículos renais bilaterais por 30 minutos, seguida de reperfusão. Ratos Wistar, machos foram usados pesando entre 250-300g, distribuídos nos seguintes grupos: SHAM (controle, sem clampeamento renal; Isquemia (isquemia renal por 30 minutos; Isquemia+Estatina (sinvastatina 0,5 mg/kg, via oral durante três dias. A função renal (clearance de creatinina, método de Jaffé, a osmolalidade urinária, os peróxidos urinários foram avaliados. RESULTADOS: Os resultados mostraram que a estatina melhorou a função renal, a osmolalidade urinária e reduziu a excreção de PU. CONCLUSÃO: Em síntese, o estudo confirmou o efeito renoprotetor da estatina, com ação antioxidante de proteção renal.OBJETIVOS: El estudio tuvo como objetivo verificar la acción renoprotectora de la simvastatina en modelo animal de isquemia/reperfusión por 30 minutos. MÉTODOS: La isquemia se obtuvo por medio del pinzamiento de los pedículos renales bilaterales por 30 minutos, seguida de la reperfusión. Fueron usadas ratas Wistar, machos que pesaban entre 250-300g, distribuidos en los siguientes grupos: SHAM (control, sin pinzamiento renal; Isquemia (isquemia renal por 30 minutos; Isquemia+Estatina (simvastatina 0,5 mg/kg, via oral durante tres días. Fueron evaluadas la función renal (clearance de creatinina, método de Jaffé, la osmolaridad urinaria y los peróxidos urinarios. RESULTADOS: Los resultados mostraron que la estatina mejoró la función renal, la osmolaridad urinaria y redujo la excreción de PU. CONCLUSIÓN: En síntesis, el estudio confirmó el efecto renoprotector de la estatina, con acción antioxidante de protección renal.OBJECTIVES: The study aimed to verify the protective renal action of simvastatin in an animal model of ischemia / reperfusion for 30

  5. THE ROLE OF MYOCARDIAL ISCHEMIC POSTCONDITIONING AND TOLL-LIKE RECEPTORS IN MYOCARDIAL REPERFUSION INJURY%心肌缺血后适应和Toll样受体在心肌再灌注损伤中的作用

    Institute of Scientific and Technical Information of China (English)

    王妮妮; 王悦喜

    2014-01-01

    近年来随着急性心肌梗死发病率的不断增高,促进了溶栓、经皮穿刺冠状动脉介入治疗和冠状动脉旁路移植术( CABG)等再灌注疗法的广泛开展,由缺血/再灌注损伤( ischemia/reperfusion injury,IRI)引起的心脏损伤日益受到重视。因此,研究减轻心肌缺血/再灌注损伤安全、有效的方法对防治心脏疾病具有重大的价值和意义。近期国内外很多研究发现心肌缺血后适应(ischemic postconditioning,IPOC)及 Toll 样受体(Toll like receptor,TRL)在心肌缺血再灌注损伤中起重要作用,本文对此进行综述。%In recent years,the thrombolysis,percutaneous coronary intervention and coronary artery bypass grafting( CABG) and other reperfusion therapy are widely developing with incidence increasing of acute myocardial infarction. Heart damage induced by the ischemia/reperfusion injury ( ischemia/reperfusion injury,IRI) is increasingly concerned. Therefore,the study of safe and effective method in reducing myocardial ischemia/reperfusion injury has great value and significance in the prevention of heart disease. Recently many domestic and foreign researches found that ischemic postconditioning (IPOC)and toll-like receptors(Toll like receptor,TRL)play important role in myocardial ischemia-reperfusion injury.

  6. Remote ischemic perconditioning prevents liver transplantation-induced ischemia/reperfusion injury in rats: Role of ROS/RNS and eNOS

    Science.gov (United States)

    He, Ning; Jia, Jun-Jun; Li, Jian-Hui; Zhou, Yan-Fei; Lin, Bing-Yi; Peng, Yi-Fan; Chen, Jun-Jie; Chen, Tian-Chi; Tong, Rong-Liang; Jiang, Li; Xie, Hai-Yang; Zhou, Lin; Zheng, Shu-Sen

    2017-01-01

    AIM To investigate the underlying mechanisms of the protective role of remote ischemic perconditioning (RIPerC) in rat liver transplantation. METHODS Sprague-Dawley rats were subjected to sham, orthotopic liver transplantation (OLT), ischemic postconditioning (IPostC) or RIPerC. After 3 h reperfusion, blood samples were taken for measurement of alanine aminotransferase, aspartate aminotransferase, creatinine (Cr) and creatinine kinase-myocardial band (CK-MB). The liver lobes were harvested for the following measurements: reactive oxygen species (ROS), H2O2, mitochondrial membrane potential (ΔΨm) and total nitric oxide (NO). These measurements were determined using an ROS/H2O2, JC1 and Total NOx Assay Kit, respectively. Endothelial NO synthase (eNOS) was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting, and peroxynitrite was semi-quantified by western blotting of 3-nitrotyrosine. RESULTS Compared with the OLT group, the grafts subjected to RIPerC showed significantly improved liver and remote organ functions (P < 0.05). ROS (P < 0.001) including H2O2 (P < 0.05) were largely elevated in the OLT group as compared with the sham group, and RIPerC (P < 0.05) reversed this trend. The collapse of ΔΨm induced by OLT ischemia/reperfusion (I/R) injury was significantly attenuated in the RIPerC group (P < 0.001). A marked increase of NO content and phosphoserine eNOS, both in protein and mRNA levels, was observed in liver graft of the RIPerC group as compared with the OLT group (P < 0.05). I/R-induced 3-nitrotyrosine content was significantly reduced in the RIPerC group as compared with the OLT group (P < 0.05). There were no significant differences between the RIPerC and IPostC groups for all the results except Cr. The Cr level was lower in the RIPerC group than in the IPostC group (P < 0.01). CONCLUSION Liver graft protection by RIPerC is similar to or better than that of IPostC, and involves inhibition of oxidative stress and up

  7. A Role for Photobiomodulation in the Prevention of Myocardial Ischemic Reperfusion Injury: A Systematic Review and Potential Molecular Mechanisms.

    Science.gov (United States)

    Liebert, Ann; Krause, Andrew; Goonetilleke, Neil; Bicknell, Brian; Kiat, Hosen

    2017-02-09

    Myocardial ischemia reperfusion injury is a negative pathophysiological event that may result in cardiac cell apoptosis and is a result of coronary revascularization and cardiac intervention procedures. The resulting loss of cardiomyocyte cells and the formation of scar tissue, leads to impaired heart function, a major prognostic determinant of long-term cardiac outcomes. Photobiomodulation is a novel cardiac intervention that has displayed therapeutic effects in reducing myocardial ischemia reperfusion related myocardial injury in animal models. A growing body of evidence supporting the use of photobiomodulation in myocardial infarct models has implicated multiple molecular interactions. A systematic review was conducted to identify the strength of the evidence for the therapeutic effect of photobiomodulation and to summarise the current evidence as to its mechanisms. Photobiomodulation in animal models showed consistently positive effects over a range of wavelengths and application parameters, with reductions in total infarct size (up to 76%), decreases in inflammation and scarring, and increases in tissue repair. Multiple molecular pathways were identified, including modulation of inflammatory cytokines, signalling molecules, transcription factors, enzymes and antioxidants. Current evidence regarding the use of photobiomodulation in acute and planned cardiac intervention is at an early stage but is sufficient to inform on clinical trials.

  8. A Role for Photobiomodulation in the Prevention of Myocardial Ischemic Reperfusion Injury: A Systematic Review and Potential Molecular Mechanisms

    Science.gov (United States)

    Liebert, Ann; Krause, Andrew; Goonetilleke, Neil; Bicknell, Brian; Kiat, Hosen

    2017-01-01

    Myocardial ischemia reperfusion injury is a negative pathophysiological event that may result in cardiac cell apoptosis and is a result of coronary revascularization and cardiac intervention procedures. The resulting loss of cardiomyocyte cells and the formation of scar tissue, leads to impaired heart function, a major prognostic determinant of long-term cardiac outcomes. Photobiomodulation is a novel cardiac intervention that has displayed therapeutic effects in reducing myocardial ischemia reperfusion related myocardial injury in animal models. A growing body of evidence supporting the use of photobiomodulation in myocardial infarct models has implicated multiple molecular interactions. A systematic review was conducted to identify the strength of the evidence for the therapeutic effect of photobiomodulation and to summarise the current evidence as to its mechanisms. Photobiomodulation in animal models showed consistently positive effects over a range of wavelengths and application parameters, with reductions in total infarct size (up to 76%), decreases in inflammation and scarring, and increases in tissue repair. Multiple molecular pathways were identified, including modulation of inflammatory cytokines, signalling molecules, transcription factors, enzymes and antioxidants. Current evidence regarding the use of photobiomodulation in acute and planned cardiac intervention is at an early stage but is sufficient to inform on clinical trials. PMID:28181487

  9. Kaempferol Attenuates Myocardial Ischemic Injury via Inhibition of MAPK Signaling Pathway in Experimental Model of Myocardial Ischemia-Reperfusion Injury

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    Kapil Suchal

    2016-01-01

    Full Text Available Kaempferol (KMP, a dietary flavonoid, has antioxidant, anti-inflammatory, and antiapoptotic effects. Hence, we investigated the effect of KMP in ischemia-reperfusion (IR model of myocardial injury in rats. We studied male albino Wistar rats that were divided into sham, IR-control, KMP-20 + IR, and KMP 20 per se groups. KMP (20 mg/kg; i.p. was administered daily to rats for the period of 15 days, and, on the 15th day, ischemia was produced by one-stage ligation of left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. After completion of surgery, rats were sacrificed; heart was removed and processed for biochemical, morphological, and molecular studies. KMP pretreatment significantly ameliorated IR injury by maintaining cardiac function, normalizing oxidative stress, and preserving morphological alterations. Furthermore, there was a decrease in the level of inflammatory markers (TNF-α, IL-6, and NFκB, inhibition of active JNK and p38 proteins, and activation of ERK1/ERK2, a prosurvival kinase. Additionally, it also attenuated apoptosis by reducing the expression of proapoptotic proteins (Bax and Caspase-3, TUNEL positive cells, and increased level of antiapoptotic proteins (Bcl-2. In conclusion, KMP protected against IR injury by attenuating inflammation and apoptosis through the modulation of MAPK pathway.

  10. Involvement of adenosine and standardization of aqueous extract of garlic (Allium sativum Linn.) on cardioprotective and cardiodepressant properties in ischemic preconditioning and myocardial ischemia-reperfusion induced cardiac injury

    Science.gov (United States)

    Sharma, Ashish Kumar; Munajjam, Arshee; Vaishnav, Bhawna; Sharma, Richa; Sharma, Ashok; Kishore, Kunal; Sharma, Akash; Sharma, Divya; Kumari, Rita; Tiwari, Ashish; Singh, Santosh Kumar; Gaur, Samir; Jatav, Vijay Singh; Srinivasan, Barthu Parthi; Agarwal, Shyam Sunder

    2012-01-01

    The present study investigated the effect of garlic (Allium sativum Linn.) aqueous extracts on ischemic preconditioning and ischemia-reperfusion induced cardiac injury, as well as adenosine involvement in ischemic preconditioning and garlic extract induced cardioprotection. A model of ischemia-reperfusion injury was established using Langendorff apparatus. Aqueous extract of garlic dose was standardized (0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.07%, 0.05%, 0.03%, 0.01%), and the 0.05% dose was found to be the most effective. Higher doses (more than 0.05%) were highly toxic, causing arrhythmia and cardiodepression, whereas the lower doses were ineffective. Garlic exaggerated the cardioprotective effect of ischemic preconditioning. The cardioprotective effect of ischemic preconditioning and garlic cardioprotection was significantly attenuated by theophylline (1,000 µmol/L) and 8-SPT (10 mg/kg, i.p.) and expressed by increased myocardial infarct size, increased LDH level, and reduced nitrite and adenosine levels. These findings suggest that adenosine is involved in the pharmacological and molecular mechanism of garlic induced cardioprotection and mediated by the modulation of nitric oxide. PMID:23554727

  11. Endoplasmic Reticulum Stress-Induced Autophagy Provides Cytoprotection from Chemical Hypoxia and Oxidant Injury and Ameliorates Renal Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Chandrika, Bhavya B; Yang, Cheng; Ou, Yang; Feng, Xiaoke; Muhoza, Djamali; Holmes, Alexandrea F; Theus, Sue; Deshmukh, Sarika; Haun, Randy S; Kaushal, Gur P

    2015-01-01

    We examined whether endoplasmic reticulum (ER) stress-induced autophagy provides cytoprotection from renal tubular epithelial cell injury due to oxidants and chemical hypoxia in vitro, as well as from ischemia-reperfusion (IR) injury in vivo. We demonstrate that the ER stress inducer tunicamycin triggers an unfolded protein response, upregulates ER chaperone Grp78, and activates the autophagy pathway in renal tubular epithelial cells in culture. Inhibition of ER stress-induced autophagy accelerated caspase-3 activation and cell death suggesting a pro-survival role of ER stress-induced autophagy. Compared to wild-type cells, autophagy-deficient MEFs subjected to ER stress had enhanced caspase-3 activation and cell death, a finding that further supports the cytoprotective role of ER stress-induced autophagy. Induction of autophagy by ER stress markedly afforded cytoprotection from oxidants H2O2 and tert-Butyl hydroperoxide and from chemical hypoxia induced by antimycin A. In contrast, inhibition of ER stress-induced autophagy or autophagy-deficient cells markedly enhanced cell death in response to oxidant injury and chemical hypoxia. In mouse kidney, similarly to renal epithelial cells in culture, tunicamycin triggered ER stress, markedly upregulated Grp78, and activated autophagy without impairing the autophagic flux. In addition, ER stress-induced autophagy markedly ameliorated renal IR injury as evident from significant improvement in renal function and histology. Inhibition of autophagy by chloroquine markedly increased renal IR injury. These studies highlight beneficial impact of ER stress-induced autophagy in renal ischemia-reperfusion injury both in vitro and in vivo.

  12. Endoplasmic Reticulum Stress-Induced Autophagy Provides Cytoprotection from Chemical Hypoxia and Oxidant Injury and Ameliorates Renal Ischemia-Reperfusion Injury.

    Directory of Open Access Journals (Sweden)

    Bhavya B Chandrika

    Full Text Available We examined whether endoplasmic reticulum (ER stress-induced autophagy provides cytoprotection from renal tubular epithelial cell injury due to oxidants and chemical hypoxia in vitro, as well as from ischemia-reperfusion (IR injury in vivo. We demonstrate that the ER stress inducer tunicamycin triggers an unfolded protein response, upregulates ER chaperone Grp78, and activates the autophagy pathway in renal tubular epithelial cells in culture. Inhibition of ER stress-induced autophagy accelerated caspase-3 activation and cell death suggesting a pro-survival role of ER stress-induced autophagy. Compared to wild-type cells, autophagy-deficient MEFs subjected to ER stress had enhanced caspase-3 activation and cell death, a finding that further supports the cytoprotective role of ER stress-induced autophagy. Induction of autophagy by ER stress markedly afforded cytoprotection from oxidants H2O2 and tert-Butyl hydroperoxide and from chemical hypoxia induced by antimycin A. In contrast, inhibition of ER stress-induced autophagy or autophagy-deficient cells markedly enhanced cell death in response to oxidant injury and chemical hypoxia. In mouse kidney, similarly to renal epithelial cells in culture, tunicamycin triggered ER stress, markedly upregulated Grp78, and activated autophagy without impairing the autophagic flux. In addition, ER stress-induced autophagy markedly ameliorated renal IR injury as evident from significant improvement in renal function and histology. Inhibition of autophagy by chloroquine markedly increased renal IR injury. These studies highlight beneficial impact of ER stress-induced autophagy in renal ischemia-reperfusion injury both in vitro and in vivo.

  13. Crosstalk between complement and Toll-like receptor activation in relation to donor brain death and renal ischemia-reperfusion injury.

    Science.gov (United States)

    Damman, Jeffrey; Daha, Mohamed R; van Son, Willem J; Leuvenink, Henri G; Ploeg, Rutger J; Seelen, Marc A

    2011-04-01

    Two central pathways of innate immunity, complement and Toll-like receptors (TLRs), play an important role in the pathogenesis of renal injury inherent to kidney transplantation. Recent findings indicate close crosstalk between complement and TLR signaling pathways. It is suggested that mitogen activated protein kinases (MAPKs) might be the key molecules linking both the complement and TLR pathways together. Complement and TLRs are important mediators of renal ischemia-reperfusion injury (IRI). Besides IRI, complement C3 can also be upregulated and activated in the kidney before transplantation as a direct result of brain death (BD) in the donor. This local upregulation and activation of complement in the donor kidney has been proven to be detrimental for renal allograft outcome. Also TLR4 and several of its major ligands are upregulated by donor BD compared to living donors. Important and in line with the observations above, kidney transplant recipients have a benefit when receiving a kidney from a TLR4 Asp299Gly/Thr399Ile genotypic donor. The role of complement and TLRs and crosstalk between these two innate immune systems in relation to renal injury during donor BD and ischemia-reperfusion are focus of this review. Future strategies to target complement and TLR activation in kidney transplantation are considered.

  14. Ischemic Postconditioning-Regulated miR-499 Protects the Rat Heart Against Ischemia/Reperfusion Injury by Inhibiting Apoptosis through PDCD4

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    Jianbing Zhu

    2016-11-01

    Full Text Available Background: Here, we determined miR-499 involvement in the protective effect of ischemic postconditioning (IPC against myocardial ischemia/reperfusion (I/R injury and identified the underlying mechanisms. Methods: To investigate the cardioprotective effect of IPC-induced miR-499, rats were divided into the following five groups: sham, I/R, IPC, IPC + scramble, and IPC + antagomiR-499. Hemodynamic indexes were measured by carotid-artery intubation to assess left ventricular function . Ischemia and infarction areas of rat hearts were determined by Evans blue and triphenyltetrazolium chloride staining, and cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end-labeling assay. Results: IPC attenuated I/R-induced infarct size of the left ventricle (45.28 ± 5.40% vs. 23.56 ± 6.20%, P vs. 990.21 ± 172.39%, P vs. 1289.11 ± 347.28%, P vs. 4.85 ± 1.52%, P in vivo and in vitro by knockdown of cardiac miR-499, suggesting that miR-499 may participate in the protective function of IPC against I/R injury through targeting programmed cell death 4 (PDCD4. Conclusion: Our data revealed that IPC-regulated miR-499 plays an important role in IPC-mediated cardiac protection against I/R injury by targeting PDCD4.

  15. Intestinal Mucosal Barrier Is Injured by BMP2/4 via Activation of NF-κB Signals after Ischemic Reperfusion

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    Kang Chen

    2014-01-01

    Full Text Available Intestinal ischemic reperfusion (I/R can cause dysfunction of the intestinal mucosal barrier; however, the mechanism of the intestinal mucosal barrier dysfunction caused by I/R remains unclear. In this study, using intestinal epithelial cells under anaerobic cultivation and an in vivo rat intestinal I/R model, we found that hypoxia and I/R increased the expression of BMP2/4 and upregulated BMP type Ia receptor and BMP type II receptor expression. We also found that exogenous BMP2/4 can activate the ERK and AKT signaling pathways in rat small intestine (IEC-6 cells, thereby activating NF-κB signaling, which leads to increased levels of inflammatory factors, such as TNF-α and IL-6. Furthermore, recombinant BMP2/4 decreased the expression of the tight junction protein occludin via the activation of the NF-κB pathway; these effects were abolished by treatment with the BMP-specific antagonist noggin or the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC. All these factors can destroy the intestinal mucosal barrier, thereby leading to weaker barrier function. On the basis of these data, we conclude that BMP2/4 may act as the pathogenic basis for intestinal mucosal barrier dysfunction when the intestines suffer an I/R injury. Our results provide background for the development pharmacologic interventions in the management of I/R injury.

  16. Effect of Curcuma longa and Ocimum sanctum on myocardial apoptosis in experimentally induced myocardial ischemic-reperfusion injury

    Science.gov (United States)

    Mohanty, Ipseeta; Arya, Dharamvir Singh; Gupta, Suresh Kumar

    2006-01-01

    Background In the present investigation, the effect of Curcuma longa (Cl) and Ocimum sanctum (Os) on myocardial apoptosis and cardiac function was studied in an ischemia and reperfusion (I-R) model of myocardial injury. Methods Wistar albino rats were divided into four groups and orally fed saline once daily (sham, control IR) or Cl (100 mg/kg; Cl-IR) or Os (75 mg/kg; Os-IR) respectively for 1 month. On the 31st day, in the rats of the control IR, Cl-IR and Os-IR groups LAD occlusion was undertaken for 45 min, and reperfusion was allowed for 1 h. The hemodynamic parameters{mean arterial pressure (MAP), heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular peak positive (+) LVdP/dt (rate of pressure development) and negative (-) LVdP/dt (rate of pressure decline)} were monitored at pre-set points throughout the experimental duration and subsequently, the animals were sacrificed for immunohistopathological (Bax, Bcl-2 protein expression & TUNEL positivity) and histopathological studies. Results Chronic treatment with Cl significantly reduced TUNEL positivity (p < 0.05), Bax protein (p < 0.001) and upregulated Bcl-2 (p < 0.001) expression in comparison to control IR group. In addition, Cl demonstrated mitigating effects on several myocardial injury induced hemodynamic {(+)LVdP/dt, (-) LVdP/dt & LVEDP} and histopathological perturbations. Chronic Os treatment resulted in modest modulation of the hemodynamic alterations (MAP, LVEDP) but failed to demonstrate any significant antiapoptotic effects and prevent the histopathological alterations as compared to control IR group. Conclusion In the present study, significant cardioprotection and functional recovery demonstrated by Cl may be attributed to its anti-apoptotic property. In contrast to Os, Cl may attenuate cell death due to apoptosis and prevent the impairment of cardiac performance. PMID:16504000

  17. A Double Blind Randomized Clinical Trial of Remote Ischemic Conditioning in Live Donor Renal Transplantation

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    Nicholson, Michael L; Pattenden, Clare J.; Barlow, Adam D.; Hunter, James P.; Lee, Gwyn; Hosgood, Sarah A.

    2015-01-01

    Abstract Ischemic conditioning involves the delivery of short cycles of reversible ischemic injury in order to induce protection against subsequent more prolonged ischemia. This randomized controlled trial was designed to determine the safety and efficacy of remote ischemic conditioning (RC) in live donor kidney transplantation. This prospective randomized clinical trial, 80 patients undergoing live donor kidney transplantation were randomly assigned in a 1:1 ratio to either RC or to a contro...

  18. Hydroxyfasudil-mediated inhibition of ROCK1 and ROCK2 improves kidney function in rat renal acute ischemia-reperfusion injury.

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    Dominik Kentrup

    Full Text Available Renal ischemia-reperfusion (IR injury (IRI is a common and important trigger of acute renal injury (AKI. It is inevitably linked to transplantation. Involving both, the innate and the adaptive immune response, IRI causes subsequent sterile inflammation. Attraction to and transmigration of immune cells into the interstitium is associated with increased vascular permeability and loss of endothelial and tubular epithelial cell integrity. Considering the important role of cytoskeletal reorganization, mainly regulated by RhoGTPases, in the development of IRI we hypothesized that a preventive, selective inhibition of the Rho effector Rho-associated coiled coil containing protein kinase (ROCK by hydroxyfasudil may improve renal IRI outcome. Using an IRI-based animal model of AKI in male Sprague Dawley rats, animals treated with hydroxyfasudil showed reduced proteinuria and polyuria as well as increased urine osmolarity when compared with sham-treated animals. In addition, renal perfusion (as assessed by (18F-fluoride Positron Emission Tomography (PET, creatinine- and urea-clearances improved significantly. Moreover, endothelial leakage and renal inflammation was significantly reduced as determined by histology, (18F-fluordesoxyglucose-microautoradiography, Evans Blue, and real-time PCR analysis. We conclude from our study that ROCK-inhibition by hydroxyfasudil significantly improves kidney function in a rat model of acute renal IRI and is therefore a potential new therapeutic option in humans.

  19. Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury

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    Han-Bin Lin

    2014-01-01

    Full Text Available Matrix metalloproteinases (MMPs significantly contribute to ischemia reperfusion (I/R injury, namely, by the degradation of contractile proteins. However, due to the experimental models adopted and lack of isoform specificity of MMP inhibitors, the cellular source and identity of the MMP(s involved in I/R injury remain to be elucidated. Using isolated adult rat cardiomyocytes, subjected to chemically induced I/R-like injury, we show that specific inhibition of MMP-2 expression and activity using MMP-2 siRNA significantly protected cardiomyocyte contractility from I/R-like injury. This was also associated with increased expression of myosin light chains 1 and 2 (MLC1/2 in comparison to scramble siRNA transfection. Moreover, the positive effect of MMP-2 siRNA transfection on cardiomyocyte contractility and MLC1/2 expression levels was also observed under control conditions, suggesting an important additional role for MMP-2 in physiological sarcomeric protein turnover. This study clearly demonstrates that intracellular expression of MMP-2 plays a significant role in sarcomeric protein turnover, such as MLC1 and MLC2, under aerobic (physiological conditions. In addition, this study identifies intracellular/autocrine, cardiomyocyte-produced MMP-2, rather than paracrine/extracellular, as responsible for the degradation of MLC1/2 and consequent contractile dysfunction in cardiomyocytes subjected to I/R injury.

  20. Prostaglandin-E1 has a protective effect on renal ischemia/reperfusion-induced oxidative stress and inflammation mediated gastric damage in rats.

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    Gezginci-Oktayoglu, Selda; Orhan, Nurcan; Bolkent, Sehnaz

    2016-07-01

    Gastrointestinal complications are frequent in renal transplant recipients. In this regard, renal ischemia/reperfusion injury (IRI)-induced gastric damage seems to be important and there is no data available on the mechanism of this pathology. Because of its anti-inflammatory and anti-oxidant properties, it can be suggested that prostaglandin-E1 (PGE1) protects cells from renal IRI-induced gastric damage. The aim of this study was to investigate the molecular mechanisms of gastric damage induced by renal IRI and the effect of PGE1 on these mechanisms. We set an experiment with four different animal groups: physiological saline-injected and sham-operated rats, PGE1 (20μg/kg)-administered and sham operated rats, renal IRI subjected rats, and PGE1-administered and renal IRI subjected rats. The protective effect of PGE1 on renal IRI-induced gastric damage was determined based on reduced histological damage and lactate dehydrogenase activity. Moreover, we demonstrated that PGE1 shows its protective effect through reducing the production of reactive oxygen species and malondialdehyde levels. During histological examination, we observed the presence of common mononuclear cell infiltration. Therefore, pro-inflammatory cytokines tumor necrosis factor-α and interleukin-1β levels were measured and it has been shown that PGE1 suppressed both cytokines. Furthermore, it was found that PGE1 reduced the number of NF-κB(+) and caspase-3(+) inflammatory cells, and also NF-κB DNA-binding activity, while increasing proliferating cell nuclear antigen(+) epithelial cells in the stomach tissue of rats subjected to renal IR. Our data showed that PGE1 has a protective effect on renal IRI-induced oxidative stress and inflammation mediated gastric damage in rats.

  1. Avaliação do efeito da clorpromazina sobre a função renal de cães submetidos à isquemia e reperfusão

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    Liliana B. de Menezes

    2010-02-01

    Full Text Available A isquemia renal está presente em diferentes situações como em cirurgias renais, vasculares e no transplante renal. O objetivo deste trabalho foi avaliar a integridade e a função renal de cães submetidos à isquemia e reperfusão com ou sem aplicação de clorpromazina. Para tanto foram utilizados 12 cães distribuídos aleatoriamente em dois grupos de seis indivíduos: grupo A com isquemia e reperfusão sem tratamento por clorpromazina e o grupo B com isquemia e reperfusão tratados previamente com clorpromazina. De cada cão foi coletado sangue e urina antes da isquemia, no inicio da reperfusão, após 120 minutos de reperfusão e semanalmente até 28º dia pós-cirúrgico para verificar possíveis efeitos tardios da isquemia/reperfusão. Avaliações da integridade e função renal foram feitas por exame físico, concentração sérica de ureia e creatinina e determinação da GGT urinária. A avaliação da relação proteína urinária/creatinina urinária (PU/CU e atividade da GGT urinária são exames mais sensíveis para detectar lesão tubular aguda que o exame de urina de rotina, uma vez que estas variáveis apresentaram alteração mais precocemente. Não houve ação protetora da clorpromazina conforme constatado por meio da urinálise, dosagens séricas de ureia e creatinina, excreção urinária de GGT e PU/CU.Renal ischemia may occur in different situations such as vascular or renal surgery and also in renal transplantation. This study evaluates renal function in dogs submitted to ischemia and reperfusion after chlorpromazine application. Twelve adult mongrel dogs were distributed into two groups with six animals each. Group A was composed of dogs submitted to renal ischemia and reperfusion without previous administration of chlorpromazine. Group B was composed of dogs with renal ischemia and reperfusion previously treated with chlorpromazine. In order to evaluate the possible ischemia/reperfusion late effects, blood and

  2. Etanercept protects myocutaneous flaps from ischaemia reperfusion injury: An experimental study in a rat tram flap model.

    Science.gov (United States)

    Ersoy, Burak; Çevik, Özge; Çilingir, Özlem Tuğçe

    2016-08-01

    Background Being an inevitable component of free tissue transfer, ischemia-reperfusion injury tends to contribute to flap failure. TNF-α is an important proinflammatory cytokine and a prominent mediator of the ischemia-reperfusion injury. Etanercept, a soluble TNF-α binding protein, has shown anti-inflammatory and anti-apoptotic effects in animal models of renal and myocardial ischemia-reperfusion injury. We have designed an experimental study to investigate the effect of etanercept on myocutaneous ischemia-reperfusion injury on transverse rectus abdominis myocutaneous flap model in rats. Methods Twenty-four male Sprague-Dawley rats were divided into 3 groups: In group 1 (sham), the TRAM flap was raised and sutured back without further intervention. In group 2 (control), the flap was raised and the ischemia-reperfusion protocol was followed. In group 3, etanercept (10 mg/kg, i.v.) was administered 10 minutes before reperfusion. At the end of the reperfusion period, biochemical and histolopathological evaluations were performed on serum and tissue samples. Results In the etanercept group the IMA and 8-OHdG levels (p = 0.005 and p = 0.004, respectively) were found significantly lower, and the GSH and SOD levels (p = 0.01 and p ischemia-reperfusion injury in skeletal muscle tissue, enhancing the TRAM flap viability. The ability of etanercept to induce ischemic tolerance suggests that it may be applicable in free-flap surgery.

  3. Recovery of renal function after administration of adipose-tissue-derived stromal vascular fraction in rat model of acute kidney injury induced by ischemia/reperfusion injury.

    Science.gov (United States)

    Lee, Chunwoo; Jang, Myoung Jin; Kim, Bo Hyun; Park, Jin Young; You, Dalsan; Jeong, In Gab; Hong, Jun Hyuk; Kim, Choung-Soo

    2017-03-10

    Acute kidney injury (AKI) induced by ischemia/reperfusion (I/R) injury is a major challenge in critical care medicine. The purpose of this study is to determine the therapeutic effects of the adipose-tissue-derived stromal vascular fraction (SVF) and the optimal route for SVF delivery in a rat model of AKI induced by I/R injury. Fifty male Sprague-Dawley rats were randomly divided into five groups (10 animals per group): sham, nephrectomy control, I/R injury control, renal arterial SVF infusion and subcapsular SVF injection. To induce AKI by I/R injury, the left renal artery was clamped with a nontraumatic vascular clamp for 40 min, and the right kidney was removed. Rats receiving renal arterial infusion of SVF had a significantly reduced increase in serum creatinine compared with the I/R injury control group at 4 days after I/R injury. The glomerular filtration rate of the renal arterial SVF infusion group was maintained at a level similar to that of the sham and nephrectomy control groups at 14 days after I/R injury. Masson's trichrome staining showed significantly less fibrosis in the renal arterial SVF infusion group compared with that in the I/R injury control group in the outer stripe (P renal arterial SVF infusion and subcapsular SVF injection groups compared with the I/R injury control group in the outer stripe (P renal function is effectively rescued from AKI induced by I/R injury through the renal arterial administration of SVF in a rat model.

  4. Expression of insulin-like growth factor-1 mRNA and protein level of corpora striata in ischemic side at the early stage of middle cerebral artery ischemia/reperfusion in rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    Huanmin Gao; Rui Zhang; Yunliang Guo

    2006-01-01

    BACKGROUND: Insulin-like growth factor-I(IGF-1), as one of the important members of growth factor family,participants in the regulation of many physiological functions and behaviors, having very strong neuroprotective effect. However, the expression of IGF-1 following cerebral ischemia/reperfusion is still disputed.OBJ ECTIVE: To observe the expression of IGF-1 and protein of corpora striata in ischemic side at the early stage of middle cerebral artery ischemia/reperfusion in rhesus monkey.DESIGN: A completely randomized grouping design, controlled animal experimentSETTING: Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University.MATERIALS: ① Totally 17 rhesus monkeys , of either gender, aged 4 to 5 years, were enrolled . Seven rhesus monkeys observed with gene chip were randomly divided into 2 groups: sham operation group (n=3)and ischemia/reperfusion group (n=4). Ten rhesus monkeys observed with in situ hybridization and immunohistochemistry method were randomly divided into 2 groups: sham operation group (n=3)and ischemia/reperfusion group (n=7). Rhesus monkeys observed under microscope were divided into 2 groups: sham operation group (n=6) and ischamia/reperfusion group (n=11). ② Materials used in the experiment: cresyl violet (Sigma Company, America); immunohistochemical reagent kit ( Huamei Bio-engineering Company); In situ hybridization reagent kit (Boshide Bio-engineering Co. Ltd, Wuhan); 12 800 dots chip (Boxing Company,Shanghai).METHODS: This experiment was carried out at the Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University from January 2001 to December 2003. ① The onset area of middle cerebral artery was blocked for 2 hours, middle cerebral artery ischemia/reperfusion models were created.② After ischemia/reperfusion for 24 hours, cerebral tissue sections of rhesus monkeys were prepared and stained with cresyl violet. Image analysis was performed with 500IW

  5. Protective Effect of the Total Flavonoids from Rosa laevigata Michx Fruit on Renal Ischemia-Reperfusion Injury through Suppression of Oxidative Stress and Inflammation.

    Science.gov (United States)

    Zhao, Lisha; Xu, Lina; Tao, Xufeng; Han, Xu; Yin, Lianhong; Qi, Yan; Peng, Jinyong

    2016-07-21

    Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Our previous studies have shown that the total flavonoids (TFs) from Rosa laevigata Michx fruit has various activities, however, there were no papers reporting the role of the TFs against renal IRI. In the present work, a hypoxia/reoxygenation (H/R) model in NRK-52E cells and ischemia-reperfusion model in rats were used. The results showed that the TFs significantly attenuated cell injury and markedly decreased serum creatinine (Cr) and blood urea nitrogen (BUN) levels in rats. Further investigation revealed that the TFs markedly decreased the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) and intracellular reactive oxygen species (ROS), up-regulated the levels of silent information regulator factor 2-related enzyme 1 (Sirt1), nuclear factor erythroid 2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1), down-regulated the levels of Kelch like ECH-associated protein-1 (Keap1) and the nuclear translocation of nuclear factor-κBp65 (NF-κBp65), and decreased the mRNA levels of interleukine-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Furthermore, inhibiting Sirt1 by siRNA showed that the role of the natural product in protecting renal IRI was significantly attenuated, suggesting that the effect of the extract against renal IRI depended on Sirt1. Taken together, the TFs has significantly nephroprotective effect against IRI by affecting Sirt1/Nrf2/NF-κB signaling pathway, which should be developed as a new therapeutic agent or food additives to treat acute kidney injury in the future.

  6. Transglutaminase 2 gene ablation protects against renal ischemic injury by blocking constant NF-{kappa}B activation

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    Kim, Dae-Seok [Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute, 111 Jungbalsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 410-769 (Korea, Republic of); Kim, Bora [Animal Sciences Branch, Research Institute, 111 Jungbalsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 410-769 (Korea, Republic of); Tahk, Hongmin [Department of Food and Nutrition, College of Human Ecology, Chung-Ang University, 72-1, Nae-ri, Daeduck-myun, Ansung, Gyeonggi-do 456-756 (Korea, Republic of); Kim, Dong-Hyun; Ahn, Eu-Ree [Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute, 111 Jungbalsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 410-769 (Korea, Republic of); Choi, Changsun [Department of Food and Nutrition, College of Human Ecology, Chung-Ang University, 72-1, Nae-ri, Daeduck-myun, Ansung, Gyeonggi-do 456-756 (Korea, Republic of); Jeon, Yoon; Park, Seo Young; Lee, Ho; Oh, Seung Hyun [Cancer Experimental Resources Branch, Division of Cancer Biology, Research Institute, 111 Jungbalsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 410-769 (Korea, Republic of); Kim, Soo-Youl, E-mail: kimsooyoul@gmail.com [Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute, 111 Jungbalsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 410-769 (Korea, Republic of)

    2010-12-17

    Research highlights: {yields} No acute renal tubular necrotic lesions were found in TGase2{sup -/-} mice with ischemic kidney injury. {yields} NF-{kappa}B activation is reduced in TGase2{sup -/-} mice with ischemic kidney injury. {yields} Hypoxic stress did not increase NF-{kappa}B activity in MEFs from TGase2{sup -/-} mice. {yields} COX-2 induction is suppressed in TGase2{sup -/-} mice with ischemic kidney injury. -- Abstract: Transglutaminase 2 knockout (TGase2{sup -/-}) mice show significantly reduced inflammation with decreased myofibroblasts in a unilateral ureteral obstruction (UUO) model, but the mechanism remains to be clarified. Nuclear factor-{kappa}B (NF-{kappa}B) activation plays a major role in the progression of inflammation in an obstructive nephropathy model. However, the key factors extending the duration of NF-{kappa}B activation in UUO are not known. In several inflammatory diseases, we and others recently found that TGase 2 plays a key role in extending NF-{kappa}B activation, which contributes to the pathogenesis of disease. In the current study, we found that NF-{kappa}B activity in mouse embryogenic fibroblasts (MEFs) from TGase2{sup -/-} mice remained at the control level while the NF-{kappa}B activity of wild-type (WT) MEFs was highly increased under hypoxic stress. Using the obstructive nephropathy model, we found that NF-{kappa}B activity remained at the control level in TGase2{sup -/-} mouse kidney tissues, as measured by COX-2 expression, but was highly increased in WT tissues. We conclude that TGase 2 gene ablation reduces the duration of NF-{kappa}B activation in ischemic injury.

  7. Effect of IL-13 on expression of IL-6 in acute renal ischemia/reperfusion injury in rats%IL-13对大鼠急性肾缺血再灌注时IL-6表达的影响

    Institute of Scientific and Technical Information of China (English)

    冯振伟; 江黎明; 陈孝文; 杨展; 吴平; 赵家明; 何惠娟

    2012-01-01

    Objective It is to observe the effects of IL - 13 on expression of IL -6 in acute renal ischemia/reperfusion injury in rats. Methods Thirty-seven male Wistar rats were randomly divided into 5 groups: sham group, I/R group, C group, T - S group and T - L group. Models of acute renal ischemic/reperfusion injury were established by blocking up kidneys blood flow in both side for 45 min and reperfusion for 24h in the rats. Rm - IL - 13 was injected into the renal arteries through the abdominal aorta in T - S group and T - L group( T - S 0. 5 μg/kg body weight, T - L 1. 5 μg/kg body weight ),normal saline instead of rm - IL -13 was injected into the renal arteries through the abdominal aorta in control group. The serum level of IL -6 and the renal expression of IL - 6 were determined in each group at 24 h post-ischemia. In addition, BUN, Cr and renal histology were also measured. Results The serum level of IL - 6 gene expression and protein production of IL - 6 in kidney decreased markedly in T - L group. Renal function and histology were significantly improved in T - L group, renal injury scores decreased significantly too. A positive correlation was found between the serum level of IL - 6, gene expression IL - 6 in kidney and BUN, SCr. Conclusion IL - 13 can inhibit the expression of IL - 6 and improve function and histology of kidney in rats with acute renal ischemia/reperfusion injury.%目的 观察白细胞介素13(IL-13)对急性缺血再灌注肾损伤大鼠IL-6表达的影响.方法 将Wistar雄性大鼠37只随机分为假手术组、I/R组、C组、T-S组和T-L组.阻断大鼠双侧肾脏血流45min,再灌注24h建立急性肾缺血再灌注模型;T-S组和T-L组于阻断血流后分别从双侧肾动脉开口注射入鼠重组白细胞介素13 0.5μg/kg和1.5μg/kg;C组以生理盐水代替.检测各组大鼠IL-6血清水平和肾脏表达情况以及肾功能和肾脏病理变化.结果 T-L组肾脏IL-6基因和蛋白表达明显减少,IL-6血清水平也

  8. Mild hypoxemia during initial reperfusion alleviates the severity of secondary energy failure and protects brain in neonatal mice with hypoxic-ischemic injury.

    Science.gov (United States)

    Niatsetskaya, Zoya V; Charlagorla, Pradeep; Matsukevich, Dzmitry A; Sosunov, Sergey A; Mayurasakorn, Korapat; Ratner, Veniamin I; Polin, Richard A; Starkov, Anatoly A; Ten, Vadim S

    2012-02-01

    Reperfusion triggers an oxidative stress. We hypothesized that mild hypoxemia in reperfusion attenuates oxidative brain injury following hypoxia-ischemia (HI). In neonatal HI-mice, the reperfusion was initiated by reoxygenation with room air (RA) followed by the exposure to 100%, 21%, 18%, 15% oxygen for 60 minutes. Systemic oxygen saturation (SaO(2)), cerebral blood flow (CBF), brain mitochondrial respiration and permeability transition pore (mPTP) opening, markers of oxidative injury, and cerebral infarcts were assessed. Compared with RA-littermates, HI-mice exposed to 18% oxygen exhibited significantly decreased infarct volume, oxidative injury in the brain mitochondria and tissue. This was coupled with improved mitochondrial tolerance to mPTP opening. Oxygen saturation maintained during reperfusion at 85% to 95% was associated (r=0.57) with the best neurologic outcome. Exposure to 100% or 15% oxygen significantly exacerbated brain injury and oxidative stress. Compared with RA-mice, hyperoxia dramatically increased reperfusion CBF, but exposure to 15% oxygen significantly reduced CBF to values observed during the HI-insult. Mild hypoxemia during initial reperfusion alleviates the severity of HI-brain injury by limiting the reperfusion-driven oxidative stress to the mitochondria and mPTP opening. This suggests that at the initial stage of reperfusion, a slightly decreased systemic oxygenation (SaO(2) 85% to 95%) may be beneficial for infants with birth asphyxia.

  9. Proximal tubule epithelial cell specific ablation of the spermidine/spermine N1-acetyltransferase gene reduces the severity of renal ischemia/reperfusion injury.

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    Kamyar Zahedi

    Full Text Available BACKGROUND: Expression and activity of spermidine/spermine N1-acetyltransferase (SSAT increases in kidneys subjected to ischemia/reperfusion (I/R injury, while its ablation reduces the severity of such injuries. These results suggest that increased SSAT levels contribute to organ injury; however, the role of SSAT specifically expressed in proximal tubule epithelial cells, which are the primary targets of I/R injury, in the mediation of renal damage remains unresolved. METHODS: Severity of I/R injury in wt and renal proximal tubule specific SSAT-ko mice (PT-SSAT-Cko subjected to bilateral renal I/R injury was assessed using cellular and molecular biological approaches. RESULTS: Severity of the loss of kidney function and tubular damage are reduced in PT-SSAT-Cko- compared to wt-mice after I/R injury. In addition, animals treated with MDL72527, an inhibitor of polyamine oxidases, had less severe renal damage than their vehicle treated counter-parts. The renal expression of HMGB 1 and Toll like receptors (TLR 2 and 4 were also reduced in PT-SSAT-Cko- compared to wt mice after I/R injury. Furthermore, infiltration of neutrophils, as well as expression of tumor necrosis factor-α (TNF-α, monocyte chemoattractant protein-1 (MCP-1 and interleukin-6 (IL-6 transcripts were lower in the kidneys of PT-SSAT-Cko compared to wt mice after I/R injury. Finally, the activation of caspase3 was more pronounced in the wt compared to PT-SSAT-Cko animals. CONCLUSIONS: Enhanced SSAT expression by proximal tubule epithelial cells leads to tubular damage, and its deficiency reduces the severity of renal I/R injury through reduction of cellular damage and modulation of the innate immune response.

  10. When stenting in renal artery stenosis? Update on pathophysiology of ischemic nephropathy and management strategies

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    Alessandro Zuccalà

    2013-11-01

    Full Text Available In recent years, decisions taken on the optimal management of patients with renal artery stenosis have triggered off controversy and debate among clinicians dealing with renovascular disease. The main reason underlying this ongoing controversy may be the heterogeneity of the clinical entities that are normally associated with the umbrella definition of renal artery stenosis. Indeed a causal link between the stenosis and its clinical consequences (i.e. hypertension, renal failure can often demonstrated in some entities, such as fibromuscular dysplasia, truncal stenosis or arterial stenosis in the transplanted kidney, which can be defined as pure renal artery stenosis. On the contrary, the entity generally called ostial stenosis is a disease of the abdominal aorta where it encroaches the ostium of the renal artery at the end of a long process involving the entire vascular tree. Patients affected by ostial stenosis also suffer from generalized atherosclerosis, and kidney damage is often caused by the atherosclerotic environment with the stenosis acting as an innocent bystander. This may account for the low rate of renal function recovery in subjects with ostial stenosis. In our view, keeping the different entities separate along with a careful understanding of the mechanisms underpinning renal damage, particularly the intrarenal activation of the renin angiotensin system which in turn induces renal inflammation and oxidative stress, may enable clinicians to make the right decisions in regard to revascularization.

  11. Ginsenoside Rd inhibits apoptosis following spinal cord ischemia/reperfusion injur y

    Institute of Scientific and Technical Information of China (English)

    Baogang Wang; Qingsan Zhu; Xiaxia Man; Li Guo; Liming Hao

    2014-01-01

    Ginsenoside Rd has a clear neuroprotective effect against ischemic stroke. We aimed to verify the neuroprotective effect of ginsenoside Rd in spinal cord ischemia/reperfusion injury and explore its anti-apoptotic mechanisms. We established a spinal cord ischemia/reperfusion injury model in rats through the occlusion of the abdominal aorta below the level of the renal artery for 1 hour. Successfully established models were injected intraperitoneally with 6.25, 12.5, 25 or 50 mg/kg per day ginsenoside Rd. Spinal cord morphology was observed at 1, 3, 5 and 7 days after spinal cord ischemia/reperfusion injury. Intraperitoneal injection of ginsenoside Rd in ischemia/reperfusion injury rats not only improved hindlimb motor function and the morphology of motor neurons in the anterior horn of the spinal cord, but it also reduced neuronal apoptosis. The optimal dose of ginsenoside Rd was 25 mg/kg per day and the optimal time point was 5 days after ischemia/reperfusion. Immunohistochemistry and western blot analysis showed ginsenoside Rd dose-de-pendently inhibited expression of pro-apoptotic Caspase 3 and down-regulated the expression of the apoptotic proteins ASK1 and JNK in the spinal cord of rats with spinal cord ischemia/reper-fusion injury. These ifndings indicate that ginsenoside Rd exerts neuroprotective effects against spinal cord ischemia/reperfusion injury and the underlying mechanisms are achieved through the inhibition of ASK1-JNK pathway and the down-regulation of Caspase 3 expression.

  12. Ischemic preconditioning

    Directory of Open Access Journals (Sweden)

    Ristić-Anđelkov Anđelka

    2005-01-01

    Full Text Available Background. Ischemic preconditioning is a phenomenon during which myocardium, subjected to brief episodes of ischemia followed by reperfusion, tolerates better the subsequent, more prolonged episode of this ischemia, thus reducing the infarction size substantially. Case report. Two patients with acute left anterior descendent artery occlusion received fibrinolytic therapy (alteplase within 6 hours of the onset of chest pain, but developed myocardial infarctions of different sizes. The first patient, without the history of preinfarction angina, developed large anterior infarct, because there was no time either for ischemic preconditioning or for the coronary collateral vessels development. In the second patient, with 4-day history of preinfarction angina, the more favorable outcome was seen he developed smaller apical necrosis, with the great degree of myocardial viability in the infarct-related area. Conclusion. Ischemic preconditioning in patients with acute myocardal infarction results in the reduction of mortality, infarction size, as well as in the frequency of malignant arrhythmias.

  13. Attenuation of Renal Ischemia-Reperfusion (I/R) Injury by Ascorbic Acid in the Canine Nephrotomy

    National Research Council Canada - National Science Library

    Jong-Man Kim; Jae-Yeon Lee; Seong-Mok Jeong; Chang-Sik Park; Myung-Cheol Kim

    2010-01-01

    ...) injury and recovery of renal function in canine nephrotomy model. In the canine model, nine mixed dogs were subjected to renal nephrotomy with premedicated ascorbic acid and hepa-saline irrigation-aspiration (treatment group 2...

  14. The ischemic/nephrotoxic acute kidney injury and the use of renal biomarkers in clinical practice.

    Science.gov (United States)

    Andreucci, Michele; Faga, Teresa; Pisani, Antonio; Perticone, Maria; Michael, Ashour

    2017-04-01

    The term Acute Renal Failure (ARF) has been replaced by the term Acute Kidney Injury (AKI). AKI indicates an abrupt (within 24-48h) decrease in Glomerular Filtraton Rate, due to renal damage, that causes fluid and metabolic waste retention and alteration of electrolyte and acid-base balance. The renal biomarkers of AKI are substances or processes that are indicators of normal or impaired function of the kidney. The most used renal biomarker is still serum creatinine that is inadequate for several reasons, one of which is its inability to differentiate between hemodynamic changes of renal function ("prerenal azotemia") from intrinsic renal failure or obstructive nephropathy. Cystatin C is no better in this respect. After the description of the pathophysiology of "prerenal azotemia" and of Acute Kidney Injury (AKI) due to ischemia or nephrotoxicity, the renal biomarkers are listed and described: urinary NAG, urinary and serum KIM-1, serum and urinary NGAL, urinary IL-18, urinary L-FABP, serum Midkine, urinary IGFBP7 and TIMP2, urinary α-GST and π-GST, urinary ɣGT and AP, urinary β2M, urinary RBP, serum and urinary miRNA. All have been shown to appear much earlier than the rise of serum Creatinine. Some of them have been demonstrated to predict the clinical outcomes of AKI, such as the need for initiation of dialysis and mortality.

  15. Ischemic ''memory image'' in acute myocardial infarction of {sup 123}I-BMIPP after reperfusion therapy. A comparison with {sup 99m}Tc-pyrophosphate and {sup 201}Tl dual-isotope SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Mochizuki, Teruhito; Miyagawa, Masao; Sugawara, Yoshifumi; Kikuchi, Takanori; Ikezoe, Junpei [Ehime Univ., Matsuyama (Japan). School of Medicine; Murase, Kenya [Osaka Univ., Suita (Japan). Medical School; Higashino, Hiroshi [Ehime Imabari Hospital (Japan)

    2002-12-01

    Ischemic ''memory image'' is a phenomenon of {sup 123}I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) in which an area at risk of acute myocardial infarction (AMI), could be detected as a defect in a couple of weeks even after successful reperfusion therapy. The purpose of this study was to clarify the incidence of the ischemic ''memory image'' of {sup 123}I-BMIPP in patients with AMI by comparing {sup 99m}Tc-pyrophosphate(PYP) and {sup 201}Tl dual-isotope SPECT. Materials consisted of 14 patients with successfully reperfused AMI and 20 patients with old myocardial infarction (OMI). All AMI patients underwent PYP/Tl dual-isotope SPECT within 1 week after the onset of AMI, and BMIPP SPECT was performed within 1 week after the PYP/Tl dual-isotope SPECT. The extent and severity of the defect of BMIPP and Tl were visually scored into four grades: 0=no defect to 3=large or severe defect. These scores were compared. PYP positive AMI lesions were concordant with BMIPP defects (13/14). In AMI, both the extent and severity scores of BMIPP were higher than {sup 201}Tl (p<0.001). Differences (BMIPP-Tl) of extent and severity scores were greater in AMI than in OMI (p<0.001). In conclusion, the ischemic ''memory image'' obtained by means of the BMIPP is a common phenomenon (13/14) in AMI, and helpful in evaluating the area at risk. (author)

  16. Exogenous alpha-1-acid glycoprotein protects against renal ischemia-reperfusion injury by inhibition of inflammation and apoptosis

    NARCIS (Netherlands)

    de Vries, B; Walter, SJ; Wolfs, TGAM; Hochepied, T; Rabina, J; Heeringa, P; Parkkinen, J; Libert, C; Buurman, WA

    2004-01-01

    Background. Although ischemia-reperfusion (I/R) injury represents a major problem in posttransplant organ failure, effective treatment is not available. The acute phase protein a-l-acid glycoprotein (AGP) has been shown to be protective against experimental I/R injury. The effects of AGP are thought

  17. Involvement of endogenous interleukin-10 and tumor necrosis factor-alpha in renal ischemia-reperfusion injury.

    NARCIS (Netherlands)

    Daemen, M.A.R.C.; van de Ven, M.W.; Heineman, E.; Buurman, W.A.

    1999-01-01

    Department of General Surgery of the University of Maastricht, The Netherlands. w.buurman@ah.unimaas.nl BACKGROUND: Ischemia followed by reperfusion is a common clinical event associated with a pro-inflammatory response leading to organ dysfunction. The aim of the present study is to evaluate the in

  18. Reperfusion pulmonary edema

    Energy Technology Data Exchange (ETDEWEB)

    Klausner, J.M.; Paterson, I.S.; Mannick, J.A.; Valeri, C.R.; Shepro, D.; Hechtman, H.B. (Harvard Medical School, Boston, MA (USA))

    1989-02-17

    Reperfusion following lower-torso ischemia in humans leads to respiratory failure manifest by pulmonary hypertension, hypoxemia, and noncardiogenic pulmonary edema. The mechanism of injury has been studied in the sheep lung lymph preparation, where it has been demonstrated that the reperfusion resulting in pulmonary edema is due to an increase in microvascular permeability of the lung to protein. This respiratory failure caused by reperfusion appears to be an inflammatory reaction associated with intravascular release of the chemoattractants leukotriene B{sub 4} and thromboxane. Histological studies of the lung in experimental animals revealed significant accumulation of neutrophils but not platelets in alveolar capillaries. The authors conclude that thromboxane generated and released from the ischemic tissue is responsible for the transient pulmonary hypertension. Second, it is likely that the chemoattractants are responsible for leukosequestration, and third, neutrophils, oxygen-derived free radicals, and thromboxane moderate the altered lung permeability.

  19. Protective effect of endothelial progenitor cells mediated by ischemic preconditioning on renal ischemic injury induced by nephron sparing surgery%缺血预适应介导的内皮祖细胞对保留肾单位手术后肾功能的保护作用

    Institute of Scientific and Technical Information of China (English)

    刘昊; 吴然; 贾瑞鹏; 朱佳庚; 吴剑平

    2013-01-01

    Objective To investigate the role of endothelial progenitor cells (EPCs) mediated by ischemic preconditioning (IPC) in renal ischemic injury in a nephron sparing surgery (NSS) rat model.Methods Ninety male Sprague-Dawley rats were randomly divided into three groups after right-side kidney nephrectomy.In sham-operated rats,lumbotomy without vascular clamping was performed; In NSS rats,renal blood vesses were clamped for 40 min and lower pole partial nephrectomy (PN) was performed; In NSS + IPC rats,besides pre-treatment with 15-min ischemia and 10-min reperfusion,the rest procedures were the same as those in NSS rats.At 1,3,6,12,24 h,and 3 days after reperfusion,the circulating pool and kidneys were harvested.The severity of renal injury,the home of EPCs,proliferation of endothelial cells as well as vascular growth factor expression was examined.Results Pretreated rats exhibited significant improvements in renal function and morphology.The histological score was significantly decreased in IPC group as compared with NSS group [(1.80 ± 0.45) vs.(3.00 ± 0.71),P < 0.05].The number of EPCs in the kidneys was increased at 12 h after reperfusion in IPC group as compared with NSS groups [(5.75 ± 0.71) % vs.(2.92 ± 0.71) %,P < 0.05].Proliferation of EPCs in peritubular capillaries was markedly increased in the kidneys treated with IPC.In addition,the expression of vascular endothelial growth factor,and stromal cell-derived factor-1α in the kidneys of pretreated rats was increased as compared with that in rats subjected to ischemic injury (P < 0.05).Conclusion IPC may attenuate renal ischemic injury induced by NSS; EPCs play an important role in renal protection,which involves promotion of endothelial cell proliferation through release of several angiogenic factors.%目的 探讨缺血预适应(IPC)介导的内皮祖细胞(EPCs)对保留肾单位手术(NSS)后肾功能的保护作用及其机制.方法 90只雄性SD大鼠随机分为对照组(Sham)、保留肾

  20. Peptidyl arginine deiminase-4 activation exacerbates kidney ischemia-reperfusion injury.

    Science.gov (United States)

    Ham, Ahrom; Rabadi, May; Kim, Mihwa; Brown, Kevin M; Ma, Zhe; D'Agati, Vivette; Lee, H Thomas

    2014-11-01

    Peptidyl arginine deiminase (PAD)4 is a nuclear enzyme that catalyzes the posttranslational conversion of arginine residues to citrulline. Posttranslational protein citrullination has been implicated in several inflammatory autoimmune diseases, including rheumatoid arthritis, colitis, and multiple sclerosis. Here, we tested the hypothesis that PAD4 contributes to ischemic acute kidney injury (AKI) by exacerbating the inflammatory response after renal ischemia-reperfusion (I/R). Renal I/R injury in mice increased PAD4 activity as well as PAD4 expression in the mouse kidney. After 30 min of renal I/R, vehicle-treated mice developed severe AKI with large increases in plasma creatinine. In contrast, mice pretreated with PAD4 inhibitors (2-chloroamidine or streptonigrin) had significantly reduced renal I/R injury. Further supporting a critical role for PAD4 in generating ischemic AKI, mice pretreated with recombinant human PAD4 (rPAD4) protein and subjected to mild (20 min) renal I/R developed exacerbated ischemic AKI. Consistent with the hypothesis that PAD4 regulates renal tubular inflammation after I/R, mice treated with a PAD4 inhibitor had significantly reduced renal neutrophil chemotactic cytokine (macrophage inflammatory protein-2 and keratinocyte-derived cytokine) expression and had decreased neutrophil infiltration. Furthermore, mice treated with rPAD4 had significantly increased renal tubular macrophage inflammatory protein-2 and keratinocyte-derived cytokine expression as well as increased neutrophil infiltration and necrosis. Finally, cultured mouse kidney proximal tubules treated with rPAD4 had significantly increased proinflammatory chemokine expression compared with vehicle-treated cells. Taken together, our results suggest that PAD4 plays a critical role in renal I/R injury by increasing renal tubular inflammatory responses and neutrophil infiltration after renal I/R.

  1. p53 participates in the protective effects of ischemic post-conditioning against OGD-reperfusion injury in primary cultured spinal cord neurons.

    Science.gov (United States)

    Li, Jinquan; Chen, Gong; Gao, Xinjie; Shen, Chao; Zhou, Ping; Wu, Xing; Che, Xiaoming; Xie, Rong

    2017-01-18

    Spinal cord ischemia-reperfusion (I/R) injury is a severe clinical condition, while the mechanism is still not clarified and the therapeutic approach is limited. Ischemia post-conditioning (PC) has been found to have the protective effects against I/R injury in brain. Recently p53 has been reported to take part in the regulation and protection of I/R injury. We hypothesize that PC has the protective effects in primary cultured spinal cord neurons against ischemia-reperfusion injury, and MDM2-p53 signaling pathway may involve in its protective mechanism. In this study, we used an OGD (oxygen and glucose deprivation)-reperfusion model in primary cultured spinal cord neurons to simulate the I/R injury of spinal cord in vitro, and PC was conducted by 3 cycles of 15min restoration of glucose and oxygen with 15min OGD, followed by 6h fully restoration as reperfusion. Lentiviral vectors were used to knock down MDM2 or over-express p53 genes in primary cultured spinal cord neurons. The results showed that 3 cycles of 15min PC generated the most significant protective effects in primary cultured spinal cord neurons against OGD-reperfusion injury. The levels of MDM2 were decreased while p53, Bax, and cleaved Caspase 3 were increased under OGD-reperfusion condition. PC could significantly reverse the down-regulation of MDM2 and up-regulation of p53, Bax, and cleaved Caspase 3 by OGD-reperfusion injury. Moreover, MDM2 knockdown or p53 over-expression could induce the cleaved Caspase 3 expression and blocked the protective effects of PC in primary cultured spinal cord neurons against OGD-reperfusion injury. In conclusion, our work demonstrated that MDM2-p53 pathway plays a pivotal role in the protective effect of PC against OGD-reperfusion injury and PC may be a feasible therapy strategy in the treatment for spinal cord I/R injury.

  2. Protective Effect of CXCR3⁺CD4⁺CD25⁺Foxp3⁺ Regulatory T Cells in Renal Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Jun, Cao; Qingshu, Li; Ke, Wei; Ping, Li; Jun, Dong; Jie, Luo; Su, Min

    2015-01-01

    Regulatory T cells (Tregs) suppress excessive immune responses and are potential therapeutic targets in autoimmune disease and organ transplantation rejection. However, their role in renal ischemia-reperfusion injury (IRI) is unclear. Levels of Tregs and expression of CXCR3 in Tregs were analyzed to investigate their function in the early phase of renal IRI. Mice were randomly divided into Sham, IRI, and anti-CD25 (PC61) + IRI groups. The PC61 + IRI group was established by i.p. injection of PC61 monoclonal antibody (mAb) to deplete Tregs before renal ischemia. CD4(+)CD25(+)Foxp3(+) Tregs and CXCR3 on Tregs were analyzed by flow cytometry. Blood urea nitrogen (BUN), serum creatinine (Scr) levels, and tubular necrosis scores, all measures of kidney injury, were greater in the IRI group than in the Sham group. Numbers of Tregs were increased at 72 h after reperfusion in kidney. PC61 mAb preconditioning decreased the numbers of Tregs and aggravated kidney injury. There was no expression of CXCR3 on Tregs in normal kidney, while it expanded at 72 h after reperfusion and inversely correlated with BUN, Scr, and kidney histology score. This indicated that recruitment of Tregs into the kidney was related to the recovery of renal function after IRI and CXCR3 might be involved in the migration of Tregs.

  3. Dosagem, In Vivo, de MetabÃlitos SanguÃneos e Tissulares de Ratos Submetidos à Isquemia Renal e a ReperfusÃo Durante a Oferta de L-Alanil-Glutamina

    OpenAIRE

    2004-01-01

    Durante a realizaÃÃo de transplantes renais e outras operaÃÃes sobre os rins ocorrem os fenÃmenos de isquemia/reperfusÃo cujos efeitos nocivos colocam em risco o sucesso dessas intervenÃÃes. Pesquisas tÃm sido feitas no sentido de controlar, ou ao menos diminuir, os efeitos indesejÃveis da isquemia/reperfusÃo. O objetivo desse estudo à avaliar o possÃvel efeito da l-alanil-glutamina sobre a isquemia/reperfusÃo renal mediante a determinaÃÃo, in vivo, das concentraÃÃes de glicose, piruv...

  4. How effective are alprostadil and hydrocortisone on reperfusion injury in kidney after distant organ ischemia?

    Directory of Open Access Journals (Sweden)

    Ali Ebrahimi

    2013-01-01

    Full Text Available Background: After reestablishment of blood flow to ischemic limb recirculation of free radicals may cause ischemia-reperfusion injury in many organs. This study designed to investigate effects of hydrocortisone and alprostadil distant injury to kidneys by both measuring biochemical markers of oxidative stress and histopathologic examination in an experimental rat model of hind limb ischemia-reperfusion. Materials and Methods: This study conducted in Isfahan University of Medical Sciences during 2011-2012. Ischemia was established by infra renal aortic clamping for 60 min in 32 male Wistar rats. Animals were divided into those receiving alprostadil (group ischemia-reperfusion plus alprostadil (IR/A, n = 8, those receiving hydrocortisone (group ischemia-reperfusion plus hydrocortisone (IR/H, n = 8, control group (group ischemia-reperfusion (IR, n = 8, and sham group (n = 8. After 120 min of reperfusion both kidneys were removed. Levels of superoxide dismutase (SOD, malondialdehyde (MDA, and glutathione (GSH as indirect markers of oxidative injury was measured. Finally all data in different groups were compared using the analysis of variance (ANOVA test by Statistical Package for Social Sciences (SPSS version 16. Results: Administration of alprostadil or hydrocortisone does not improve the biochemical parameters of oxidative injury including MDA and SOD. However, statistically significant difference was seen in GSH level among sham and IR groups. Mean (΁ standard deviation (SD concentration of GSH in IR, IR/A, IR/H, and sham groups were 1028.77 (72.65, 924.82 (70.66, 1000.28 (108.77, and 846.69 (163.52, respectively (P = 0.015. Histopathological study of specimens did not show any significant changes between groups. Conclusion: Alprostadil and hydrocortisone do not improve the kidney GSH, SOD, and MDA level and kidney releases its GSH reserve during ischemia-reperfusion event, and another point is that, 3 h of ischemia-reperfusion does not develop

  5. Avaliação metabólica das lesões de isquemia e reperfusão cerebrais após oclusão bilateral das artérias carótidas comuns: estudo experimental em ratos Metabolic evaluation of ischemic and reperfusion brain injury following bilateral occlusion of common carotid arteries: an experimental study in rats

    Directory of Open Access Journals (Sweden)

    Luiz Roberto Franklin Muniz

    2004-10-01

    of reperfusion, becoming evident the recovery of cell respiration by fosforilation pathway. CONCLUSIONS: The proposed experimental model produced partial transitory global ischemia, with systemic repercussions. The greatest metabolic alterations were verified in the initial minutes of reperfusion, typifying reperfusion injury. Such observations prove its value as an important instrument in the study of physiopathology and therapeutic sources of ischemic cerebrovascular disease.

  6. Proteome analysis of acute kidney injury - Discovery of new predominantly renal candidates for biomarker of kidney disease.

    Science.gov (United States)

    Malagrino, Pamella Araujo; Venturini, Gabriela; Yogi, Patrícia Schneider; Dariolli, Rafael; Padilha, Kallyandra; Kiers, Bianca; Gois, Tamiris Carneiro; Cardozo, Karina Helena Morais; Carvalho, Valdemir Melechco; Salgueiro, Jéssica Silva; Girardi, Adriana Castello Costa; Titan, Silvia Maria de Oliveira; Krieger, José Eduardo; Pereira, Alexandre Costa

    2017-01-16

    The main bottleneck in studies aiming to identify novel biomarkers in acute kidney injury (AKI) has been the identification of markers that are organ and process specific. Here, we have used different tissues from a controlled porcine renal ischemia/reperfusion (I/R) model to identify new, predominantly renal biomarker candidates for kidney disease. Urine and serum samples were analyzed in pre-ischemia, ischemia (60min) and 4, 11 and 16h post-reperfusion, and renal cortex samples after 24h of reperfusion. Peptides were analyzed on the Q-Exactive™. In renal cortex proteome, we observed an increase in the synthesis of proteins in the ischemic kidney compared to the contralateral, highlighted by transcription factors and epithelial adherens junction proteins. Intersecting the set of proteins up- or down-regulated in the ischemic tissue with both serum and urine proteomes, we identified 6 proteins in the serum that may provide a set of targets for kidney injury. Additionally, we identified 49, being 4 predominantly renal, proteins in urine. As prove of concept, we validated one of the identified biomarkers, dipeptidyl peptidase IV, in a set of patients with diabetic nephropathy. In conclusion, we identified 55 systemic proteins, some of them predominantly renal, candidates for biomarkers of renal disease.

  7. Effects of reperfusion arrhythmias and myocardial connexin 43 by Compound Astragalus Mixture Nourishing Heart in a rat model of acute myocardial ischemic reperfusion injury%复方黄芪养心合剂对大鼠缺血再灌注心肌缝隙连接蛋白43的影响

    Institute of Scientific and Technical Information of China (English)

    陈启兰; 龚一萍; 祝光礼; 齐国安; 赫小龙; 任兴昌; 王骋

    2013-01-01

    目的:观察复方黄芪养心合剂对SD大鼠缺血再灌注心肌细胞缝隙连接蛋白43(Cx43)分布的改变和表达的影响.方法:应用复方黄芪养心合剂按每天14g/kg剂量、琥珀酸美托洛尔缓释片按每天(MSSRT) 9.5mg/kg剂量灌胃2周后,对SD大鼠行冠状动脉左前降支结扎30min后再灌注60min造成心肌缺血再灌注(I/R)损伤模型,记录Ⅱ导联心电图,采用免疫组织化学法(IHC)观察心肌细胞Cx43分布的改变;运用Image Pro Plus 6.0图像分析软件对Cx43的表达进行半定量分析.结果:Cx43平均光密度(AOD)I/R组心肌内膜下缺血区Cx43的AOD显著低于假手术组(P<0.01),且MSSRT组、复方组较1/R组升高(P<0.05).结论:对冠状动脉左前降支结扎术后再灌注SD大鼠,复方黄芪养心合剂对心肌细胞Cx43分布的改变有改善作用,有促进心肌内膜下缺血区域Cx43表达的作用,其作用与MSSRT相近.%Objective: To evaluate the effects of Compound Astragalus Mixture Nourishing Heart (CAMNH) antiarrhythmia and myocardial connexin 43 (Cx43) in a rat model of acute myocardial ischemic reperfusion injury. Methods: Myocardial infarction (MI) was induced by ligating left anterior descending coronary artery (LAD) for 30 minutes, followed by reperfusion of 60 minutes in rats. Rats were treated with CAMNH (14g·kg-1·d-1) or metoprolol succinate sustained-release tablets (MSSRT, 9.5mg·kg-1d-1) for 14 days before MI. The distribution of myocardial Cx43 was observed by Immunohistochemistry (IHC), and the expression of myocardial Cx43, which were represented by average optical density (AOD), was measured by Image Pro Plus 6.0. Results: The expression of myocardial Cx43 in infarction region was significantly reduced, disordered and even all disappearing, the expression of myocardial Cx43 from infarction region into ischemic region and normal region had a gradual recovery of transitional variability. Ischemia/reperfusion(I/R) group vs sham-operated (SO

  8. The effect of ischemic postconditioning on cerebral ischemia-reperfusion injury in diabetic rats%缺血后处理对糖尿病大鼠局灶性脑缺血再灌注损伤的影响

    Institute of Scientific and Technical Information of China (English)

    卢英云; 王翠兰; 刘颖; 李燕

    2008-01-01

    Objective To observe the effect of ischemic postconditioning on cerebral ischemia-reperfusion (I/R)injury in diabetic rats. Methods A rat model of diabetes was established using a single intraperitoneal injection of streptozotocin in 40 male Spragne-Dawley rats.Focal ischemia was induced by transient middle cerebral artery occlusion(MCAO)using a thread.The rats were randomly assigned to a control group,a sham-operated group,an I/R group and an Ⅰ-Post group.The animals in the I/R group were subjected to MCAO for 90 min and then reperfusion.Those in the Ⅰ-post group were subjected to MCAO and 3 cycles of transient ischemia-reperfusion(15 seconds ischemia then 15 seconds reperfusion)before persistent reperfusion.Neurological deficit scores,infarct volume,histological changes in the brain and the number of apoptotic cells were measured 6 hours later.Results There was no significant difference in neurological deficit scores between the I/R group and the Ⅰ-post group.The histological changes and apoptotic cells were significantly less in the Ⅰ-post group compared with the I/R group.Conclusion Ischemic postconditioning can inhibit cell apoptosis and reduce cerebral I/R injury after focal cerebral ischemia-reperfusion in diabetic rats.%目的 探讨缺血后处理(Ⅰ-Post)对糖尿病大鼠局灶性脑缺血再灌注(L/R)损伤的影响.方法 采用链脲佐菌(STZ)腹腔注射方式建立糖尿病大鼠模型,将制模成功的糖尿病大鼠随机分为4组,即空白对照组、假手术组、缺血再灌注组(Ⅰ/R组)及缺血后处理组(Ⅰ-Post组).Ⅰ/R组及Ⅰ-Post组均通过线栓法制作大鼠大脑中动脉阻塞(MCAO)模型,并且Ⅰ-Post组于大脑中动脉阻塞90 min后,反复进行3次短暂再灌注干预(灌注15 s后缺血15 s);假手术组手术步骤同上,但不插入线栓;空白对照组不给予任何处理.于缺血90 min、再灌注6 h后对所有大鼠进行神经功能评分(NDS)、脑梗死体积测定、观察脑组织神经

  9. Stanniocalcin-1 inhibits renal ischemia/reperfusion injury via an AMP-activated protein kinase-dependent pathway

    Science.gov (United States)

    AKI is associated with increased morbidity, mortality, and cost of care, and therapeutic options remain limited. Reactive oxygen species are critical for the genesis of ischemic AKI. Stanniocalcin-1 (STC1) suppresses superoxide generation through induction of uncoupling proteins (UCPs), and transgen...

  10. 再灌注抢救激酶在肥厚心肌缺血后适应中的作用%Ischemic postconditioning protects hypertrophic myocardium by reperfusion injury salvage kinase in mice

    Institute of Scientific and Technical Information of China (English)

    李晓梅; 杨毅宁; 马依形; 陈邦党; 刘芬; 韩伟; 高晓明

    2011-01-01

    目的 探讨再灌注抢救激酶细胞外信号调节激酶1/2(ERK1/2 )和磷脂酸肌醇3激酶-蛋白激酶B(PI3 K-Akt)信号通路在缺血后适应(Most )对减轻肥厚心肌缺血再灌注(I/R)损伤中的作用.方法 12周龄C57/BI刁、鼠通过主动脉弓缩窄4周建立心肌肥厚模型,利用Langendor"灌流装置建立小鼠肥厚心肌I/R模型,30 min全心缺血随后再灌注15、120 min.分为缺血再灌注组(I/R组)、后适应组(Most组,采取缺血10 s及再灌注10s的3次Most周期),I/R+抑制剂组[分别加人ERK1/2特异性抑制剂PD98058,Akt特异性抑制剂握曼青霉素(wortmannin)],IPost+抑制剂组,进行心脏血流动力学检测,采用三苯基氯化四氮哇染色的方法确定心肌梗死范围,免疫印迹方法检测ERK1/2,p70s6k,Akt、糖原合成酶3阿GSK-3团总蛋白及磷酸化蛋白表达水平.结果 与I/R组比较,Most组小鼠心脏血流动力学指标左心室收缩压、左室压力上升最大速度显著改善[(67±5)比(86±6),(2720±210)比(3678±330)mm Hg,均P0.05);Most+PD98058组显示在再灌注的最初15 min使用PD98059能消除Most对肥厚心肌的上述保护作用.与I/R组比较,IPost组再灌注15、120 min心肌的Akt,GSK-3β蛋白磷酸化水平表达差异无统计学意义(均P>O.05);I/R+wortmannin组、IPost+wortmannin组上述指标差异亦无统计学意义(均P>O.05).结论 IPost能有效地减轻离体小鼠肥厚心肌缺血再灌注损伤,ERK1 /2细胞信号途径是IPost对缺血再灌注肥厚心肌保护作用的重要信号通路;而PI3K-Akt信号通路未参与IPost上述保护作用.%Objective To determine the effect of ischemic postconditioning (IPost) protection in hypertrophic myocardium subjected to ischemic-reperfusion (I/R) injury and to study the role of reperfusion injury salvage kinase (RISK) in mediating such protection. Methods Transversing aortic constriction (TAC) was induced for 4 weeks in 12 weeks old C57/BL mice to establish left ventricular hypertrophy

  11. Effect of NADPH oxidase inhibitor-apocynin on the expression of Src homology-2 domain-containing phosphatase-1 (SHP-1 exposed renal ischemia/reperfusion injury in rats

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    Zhiming Li

    2015-01-01

    Full Text Available This study was designed to evaluate whether NADPH oxidase inhibitor (apocynin preconditioning induces expression of Src homology-2 domain-containing phosphatase-1 (SHP-1 to protect against renal ischemia/reperfusion (I/R injury (RI/RI in rats. Rats were pretreated with 50 mg/kg apocynin, then subjected to 45 min ischemia and 24 h reperfusion. The results indicated that apocynin preconditioning improved the recovery of renal function and nitroso-redox balance, reduced oxidative stress injury and inflammation damage, and upregulated expression of SHP-1 as compared to RI/RI group. Therefore our study demonstrated that apocynin preconditioning provided a protection to the kidney against I/R injury in rats partially through inducing expression of SHP-1.

  12. The Effect of the Antioxidant Drug “U-74389G” on Creatinine Levels during Ischemia Reperfusion Injury in Rats

    Science.gov (United States)

    Tsompos, Constantinos; Panoulis, Constantinos; Toutouzas, Konstantinos; Zografos, George; Papalois, Apostolos

    2016-01-01

    Objective The aim of this experimental study was to examine the effect of the antioxidant drug “U-74389G” on a rat model using an ischemia reperfusion protocol. The effect of U-74389G was studied biochemically by measuring mean blood creatinine levels. Materials and Methods Forty rats were used in the study. Creatinine levels were measured at 60 min of reperfusion (groups A and C) or at 120 min of reperfusion (groups B and D), where groups A and B were controls and groups C and D received U-74389G administration. Results U-74389G administration significantly decreased the predicted creatinine levels by 21.02 ± 5.06% (p = 0.0001). Reperfusion time non-significantly increased the predicted creatinine levels by 4.20 ± 6.12% (p = 0.4103). However, U-74389G administration and reperfusion time together produced a significant combined effect in decreasing the predicted creatinine levels by 11.69 ± 3.16% (p = 0.0005). Conclusion Independent of reperfusion time, U-74389G administration significantly decreased the creatinine levels in an ischemic rat model. This study demonstrates that short-term U-74389G administration improves renal function by increasing creatinine excretion. PMID:27390579

  13. Comparison of the effects of ischemic preconditioning and limb remote ischemic postconditioning on inflammatory response during myocardial ischemia/reperfusion injury in rats in vivo%缺血预处理和肢体远隔缺血后处理对大鼠心肌缺血/再灌注损伤中炎症反应影响的比较

    Institute of Scientific and Technical Information of China (English)

    王强; 李杉; 薛富善; 袁玉静; 熊军; 程怡; 李瑞萍; 廖旭; 刘建华

    2013-01-01

    Objective To compare the effects of ischemic preconditioning with limb remote ischemic postconditioning on inflammatory response during myocardial ischemia/reperfusion injury (I/RI) in rat in vivo.Methods Eighty male Sprague-Dawley rats weighing 250 g-350 g were randomly allocated into four groups (n=20 in each group):sham group (S group); ischemia reperfusion group (I/R group); ischemic preconditioning group (IPC group) and limb remote ischemic postconditioning group (LRIPOC group).In the groups other than the sham group,the myocardial ischemia reperfusion model was preparated by ligation of left anterior descending coronary artery for 30 min followed by 120 min reperfusion.During the process of ischemia and reperfusion,HR and MAP were recorded and the rate pressure product (RPP) at every measuring point was calculated as the index of myocardial oxygen consumption.In ten rats randomly selected from each group,the blood samples were collected from jugular vein at 30,60 min and 120 min after reperfusion.Then,serum concentrations of cardiac troponin I (cTnI),creatine kinase-MB (CK-MB),tumor necrosis factor αt (TNF-α),high mobility group box-1 protein (HMGB-1),intercellular adhesion molecule 1 (ICAM-1),interleukin1 (IL-1),IL-6 and IL-10 were all assessed.At the end of experiment,the infarct volumes were assessed by evans blue and triphenyltetrazolium chloride (TTC) staining.In another ten rats randomly selected from each group,the myocardial contents of TNF-α,HMGB-1,ICAM-1,IL-1,IL-6 and IL-10 in ischemic and non-ischemic regions were all measured after the rats were euthanized.Results The infarct volume was (72±9)% in I/R group,(36±13)% in IPC group,and (57±9)% in LRIPOC group,respectively.And the serum concentration of cTnI was (0.99 ± 0.14) μg/L in I/R group,(0.37 ±0.08) μg/L in IPC group,and (0.54±0.07) μg/L in LRIPOC group,separately.In addition,the serum concentration of CK-MB was (110±13) μg/L in I/R group,(38±8) μ g/L in IPC group,and (45

  14. Limited Clinical Utility of Remote Ischemic Conditioning in Renal Transplantation: A Meta-Analysis of Randomized Controlled Trials

    Science.gov (United States)

    Wu, Ran; Xin, Hui; Lu, Tian-Ze; Li, Ming-Hao; Song, Kai-Wei; Wang, Min; Zhu, Yun-Peng; Zhu, Meng; Geng, Li-Guo; Gao, Xiao-Fei; Zhou, Liu-Hua; Zhang, Sheng-Li; Zhu, Jia-Geng; Jia, Rui-Peng

    2017-01-01

    Objective We conducted this meta-analysis of randomized controlled trials (RCTs) to investigate whether remote ischemic conditioning (RIC) could improve graft functions in kidney transplantation. Methods PubMed, Web of Science, and Cochrane Library were comprehensively searched to identify all eligible studies by October 5, 2016. The treatment effects were examined with risk ratio (RR) and weighted mean difference with the corresponding 95% confidence intervals (CI). The statistical significance and heterogeneity were assessed with both Z-test and Q-test. Results A total of six RCTs including 651 recipients, were eventually identified. Compared to the controls, RIC could reduce the incidence of delayed graft function (DGF) after kidney transplantation (random-effects model: RR = 0.89; fixed-effect model: RR = 0.84). However, the decrease did not reveal statistical significance. The subgroup analysis by RIC type demonstrated no significant difference among the three interventions in protecting renal allografts against DGF. Furthermore, no significant difference could be observed in the incidence of acute rejection, graft loss, 50% fall in serum creatinine, as well as the estimated glomerular filtration rate and hospital stay between the RIC and Control groups. Conclusions This meta-analysis suggested that RIC might exert renoprotective functions in human kidney transplantation, and further well-designed RCTs with large sample size are warranted to assess its clinical efficacy. PMID:28129389

  15. Thoracic combined spinal epidural anesthesia for laparoscopic cholecystectomy in a geriatric patient with ischemic heart disease and renal insufficiency.

    Science.gov (United States)

    Mehta, Nandita; Gupta, Sunana; Sharma, Atul; Dar, Mohd Reidwan

    2015-01-01

    Older people undergoing any surgery have a higher incidence of morbidity and mortality, resulting from a decline in physiological reserves, associated comorbidities, polypharmacy, cognitive dysfunction, and frailty. Most of the clinical trials comparing regional versus general anesthesia in elderly have failed to establish superiority of any single technique. However, the ideal approach in elderly is to be least invasive, thus minimizing alterations in homeostasis. The goal of anesthetic management in laparoscopic procedures includes management of pneumoperitoneum, achieving an adequate level of sensory blockade without any respiratory compromise, management of shoulder tip pain, provision of adequate postoperative pain relief, and early ambulation. Regional anesthesia fulfills all the aforementioned criteria and aids in quick recovery and thus has been suggested to be a suitable alternative to general anesthesia for laparoscopic surgeries, particularly in patients who are at high risk while under general anesthesia or for patients unwilling to undergo general anesthesia. In conclusion, we report results of successful management with thoracic combined spinal epidural for laparoscopic cholecystectomy of a geriatric patient with ischemic heart disease with chronic obstructive pulmonary disease and renal insufficiency.

  16. Thoracic combined spinal epidural anesthesia for laparoscopic cholecystectomy in a geriatric patient with ischemic heart disease and renal insufficiency

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    Mehta N

    2015-12-01

    Full Text Available Nandita Mehta, Sunana Gupta, Atul Sharma, Mohd Reidwan Dar Department of Anesthesiology and Intensive Care, Acharya Shri Chander College of Medical Sciences and Hospital, Jammu, Jammu and Kashmir, India Abstract: Older people undergoing any surgery have a higher incidence of morbidity and mortality, resulting from a decline in physiological reserves, associated comorbidities, polypharmacy, cognitive dysfunction, and frailty. Most of the clinical trials comparing regional versus general anesthesia in elderly have failed to establish superiority of any single technique. However, the ideal approach in elderly is to be least invasive, thus minimizing alterations in homeostasis. The goal of anesthetic management in laparoscopic procedures includes management of pneumoperitoneum, achieving an adequate level of sensory blockade without any respiratory compromise, management of shoulder tip pain, provision of adequate postoperative pain relief, and early ambulation. Regional anesthesia fulfills all the aforementioned criteria and aids in quick recovery and thus has been suggested to be a suitable alternative to general anesthesia for laparoscopic surgeries, particularly in patients who are at high risk while under general anesthesia or for patients unwilling to undergo general anesthesia. In conclusion, we report results of successful management with thoracic combined spinal epidural for laparoscopic cholecystectomy of a geriatric patient with ischemic heart disease with chronic obstructive pulmonary disease and renal insufficiency. Keywords: geriatric anesthesia, bupivacaine, segmental anesthesia, laparoscopic surgery

  17. 缺血后处理对大鼠小肠缺血-再灌注损伤的保护作用%Protective effect of ischemic postconditioning on the intestinal ischemia-reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    袁勇; 郭皓; 张毅; 甘平; 周东; 陈嘉勇

    2011-01-01

    Objective To investigate protective effect and mechanism of ischemic postconditioning on the rat model of intestinal ischemiareperfusion.Methods Forty healthy SPF male rats were randomly divided into four groups.The sham group, which underwent a laparotomy and dissection of superior mesenteric artery(SMA) hefore the peritoneal cavity was closed : the IR group,undergoing mesenterte ischemia(45 minutes) and reperfusion(two hours) ;the IPr group,three cycles of tschemia alternated with three cycles of reperfusion lasting two minutes each were performed before 45 minutes ischemia and 120 minutes reperfusion; and the IPo group, undergoing ischemia(45 minutes) and reperfusion(two hours) (before the beginning of reperfusion, three cycles of reperfusion alternated with three cycles of ischemia lasting two minutes each were performed.At the end of procedure.the intestinal mor phometric study was measured by ChiU's classification,the TNF-α,IL-1β,IL-6 and IL-10 in serum were measured by FLISA and the colony forming units/g(CFU/g) were counted.Results The degree of pathological impaired of small intestine in IPr and IPo groups were lighter than IR group(P<0.05).The IPr and IPo rats had enhancement of IL-10 and suppressed production of serum TNF-α,IL-1β and IL-6 ,compared to IR group rats(P<0.05).The E.coli DH5α was hardly detected in the S group.And the levels of bacterial translocation in the IR group were higher than those of IPr and IPo groups(P<0.05).Conclusion The IPo has a positive effect on lessening intestinal mucosa injury, on inhibiting secretion of proinflammatory cytokines , and reducing levels of the bacterial translocation.%目的 探讨缺血后处理(IPo)对大鼠小肠缺血-再灌注损伤的保护作用.方法 40只健康无特殊病原体级雄性SD大鼠随机分为4组.S组:假手术组;IR组:缺血-再灌注组,夹闭肠系膜上动脉(SMA)45 min,再灌注2 h;IPr组:缺血预处理组,分离SMA后给予3个循环的缺血及再灌注各2 min

  18. Ischemia-reperfusion histopathology alterations of the rabbit intestinal wall with and without ischemic preconditioning Alterações histopatológicas da parede intestinal de coelhos na isquemia-reperfusão com e sem precondicionamento isquêmico

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    Otoni Moreira Gomes

    2011-08-01

    Full Text Available PURPOSE: To evaluate the histopathology alterations of the intestinal mucosa of rabbits submitted to mesenteric artery ischemia and reperfusion with and without ischemic preconditioning. METHODS: Two groups of ten male New Zealand white rabbits body (weight 2.2-3.0, average 2.5 kg. For mesenteric ischemia induction in all animals the small bowel and mesentery were cut 30cm and 60cm far from the gastroduodenal pyloric transition before the proximal mesenteric artery occlusion. In the Group 1 animals, the proximal mesenteric artery was occluded for 45 min with an atraumatic vascular clamp, followed by reperfusion for 30 min. In the Group 2 the 45 min ischemic phase was preceded by three cycles of ischemia (2 minutes each alternated with three cycles of reperfusion (2 minutes each. For istopathology study small bowel biopsies were obtained before ischemia (control, after 45 min of mesenteric ischemia and at 30 min. of mesenteric artery reperfusion. RESULTS: In the Group I animals, the followings histopathology grade results were observed: t1, mean 2,8; t2, mean 3,3. Using the Kruskal-Wallis non-parameter test, differences between t0 and t1 and t0 and t2 were significants (p0.05. In the Group 2 animals histopathology grade results were: t1 mean 2,6 and t2, mean 2,1. Differences between t0 and t1, t0 and t2 were significant (p0.05 between results of t1 in both groups but histopathology injury observed in Group 1 t2 biopsies were higher (pOBJETIVO: Avaliar as alterações histopatológicas da mucosa intestinal de coelhos submetidos a isquemia-reperfusão com e sem precondicionamento isquêmicol. MÉTODOS: Foram estudados dois grupos de dez coelhos Nova Zelândia machos com pesos variáveis entre 2,2 e 3,0 kg (média de 2,5 kg de peso corpóreo. Para indução da isquemia, em todos os animais, o intestino delgado e o mesentério foram seccionados 30 cm e 60 cm após a transição pilórica gastroduodenal, antes da oclusão da artéria mesent

  19. Research progress of the mechanism of cerebral ischemic reperfusion injury%脑梗死缺血再灌注损伤机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    陈念; 王立平

    2014-01-01

    Cerebral ischemia reperfusion injury is a research hotspot of acute cerebral infarction at present,and its mechanism is complex.In recent years,the study found that cerebral ischemia reperfusion injury has relationship with Na +-K +-ATP enzyme, glutathione peroxidase,nitric oxide synthas,peroxisome proliferators activated receptor gamma,Caspase-3,aquapon-4 and so on. Through this research,we can give intervention measures as soon as possible,reduce the degree of reperfusion injury after cerebral infarction,save more brain death,improve the ability of daily life of the patients.%脑缺血再灌注损伤是目前急性脑梗死的研究热点,其机制较复杂,近年来不断有研究发现脑缺血再灌注损伤还与Na+-K+-ATP酶、谷胱甘肽过氧化物酶、一氧化氮合酶、过氧化物酶体增殖受体γ、Caspase-3、水通道蛋白4等有关。通过这些研究,可以尽早地给予干预措施,减轻脑梗死后再灌注损伤的程度,挽救更多的濒死脑组织,提高患者日常生活能力。

  20. Beneficial effects of thymoquinone and omega-3 on intestinal ischemia/reperfusion-induced renal dysfunction in rats

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    Ahmed M. Fayez

    2014-12-01

    Depending on the obtained results in the present study it could be concluded that thymoquinone and omega-3 have beneficial effects on II/R-induced renal dysfunction in rats. The protective potential could be attributed to the antioxidant, antiapoptotic and anti-inflammatory effects of test drugs.

  1. [Free radicals and hepatic ischemia-reperfusion].

    Science.gov (United States)

    Szijártó, Attila

    2015-11-22

    The critical importance of the ischemic-reperfusive injury is well documented with regards to numerous organs and clinical conditions. Oxygen free radicals play a central role in the mediation of the injury, which dominantly influences the prevalence of postoperative complications, (long term) organ damage, and the potential manifestation of systemic reactions. The both anatomically and pathophysiologically unique ischemic-reperfusive injury of the liver, which is expressively vulnerable to free radicals, is of utmost importance in liver surgery. Several techniques (adaptive maneuvers, chemical agents) are known to ameliorate the reperfusive injury. Based on the prior research of the workgroup of the author, the aim of the current article is to overview the set of measures capable of attenuating ischemic-reperfusive injury (ischemic preconditioning, -perconditioning, administration of adenosine, -inosine, -levosimendan, and -poly-ADP-ribose-polymerase inhibitor), with special attention to the ischemic-reperfusive injury of the liver, as well as the special pathophysiological role of free radicals in mediating hepatic damage.

  2. Inflammatory Mechanisms of Organ Crosstalk during Ischemic Acute Kidney Injury

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    Laura E. White

    2012-01-01

    Full Text Available Acute kidney injury (AKI is a common complication during inpatient hospitalization, and clinical outcomes remain poor despite advancements in renal replacement therapy. AKI in the setting of multiple organ failure (MOF remains a formidable challenge to clinicians and incurs an unacceptably high mortality rate. Kidney ischemia-reperfusion injury (IRI incites a proinflammatory cascade and releases cellular and soluble mediators with systemic implications for remote organ injury. Evidence from preclinical models cites mechanisms of organ crosstalk during ischemic AKI including the expression of cellular adhesion molecules, lymphocyte trafficking, release of proinflammatory cytokines and chemokines, and modification of the host innate and adaptive immune response systems. In this paper, the influence of kidney IRI on systemic inflammation and distant organ injury will be examined. Recent experimental data and evolving concepts of organ crosstalk during ischemic AKI will also be discussed in detail.

  3. The effect of insulin-loaded linear poly(ethylene glycol)-brush-like poly(l-lysine) block copolymer on renal ischemia/reperfusion-induced lung injury through downregulating hypoxia-inducible factor.

    Science.gov (United States)

    Tong, Fei; Tang, Xiangyuan; Li, Xin; Xia, Wenquan; Liu, Daojun

    2016-01-01

    The aim of this study was to observe the therapeutic effect of insulin-loaded linear poly(ethylene glycol)-brush-like poly(l-lysine) block copolymer poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(l-lysine)) (PEG-b-(PELG-g-PLL) on renal ischemia/reperfusion-induced lung injury through downregulating hypoxia-inducible factor (HIF) as compared to free insulin. Sprague Dawley rats were pretreated with 30 U/kg insulin or insulin/PEG-b-(PELG-g-PLL) complex, and then subjected to 45 minutes of ischemia and 24 hours of reperfusion. The blood and lungs were collected, the level of serum creatinine and blood urea nitrogen were measured, and the dry/wet lung ratios, the activity of superoxide dismutase and myeloperoxidase, the content of methane dicarboxylic aldehyde and tumor necrosis factor-α, and the expression of HIF-1α and vascular endothelial growth factor (VEGF) were measured in pulmonary tissues. Both insulin and insulin/PEG-b-(PELG-g-PLL) preconditioning improved the recovery of renal function, reduced pulmonary oxidative stress injury, restrained inflammatory damage, and downregulated the expression of HIF-1α and VEGF as compared to ischemia/reperfusion group, while insulin/PEG-b-(PELG-g-PLL) significantly improved this effect.

  4. The effect of insulin-loaded linear poly(ethylene glycol)-brush-like poly(l-lysine) block copolymer on renal ischemia/reperfusion-induced lung injury through downregulating hypoxia-inducible factor

    Science.gov (United States)

    Tong, Fei; Tang, Xiangyuan; Li, Xin; Xia, Wenquan; Liu, Daojun

    2016-01-01

    The aim of this study was to observe the therapeutic effect of insulin-loaded linear poly(ethylene glycol)-brush-like poly(l-lysine) block copolymer poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(l-lysine)) (PEG-b-(PELG-g-PLL) on renal ischemia/reperfusion-induced lung injury through downregulating hypoxia-inducible factor (HIF) as compared to free insulin. Sprague Dawley rats were pretreated with 30 U/kg insulin or insulin/PEG-b-(PELG-g-PLL) complex, and then subjected to 45 minutes of ischemia and 24 hours of reperfusion. The blood and lungs were collected, the level of serum creatinine and blood urea nitrogen were measured, and the dry/wet lung ratios, the activity of superoxide dismutase and myeloperoxidase, the content of methane dicarboxylic aldehyde and tumor necrosis factor-α, and the expression of HIF-1α and vascular endothelial growth factor (VEGF) were measured in pulmonary tissues. Both insulin and insulin/PEG-b-(PELG-g-PLL) preconditioning improved the recovery of renal function, reduced pulmonary oxidative stress injury, restrained inflammatory damage, and downregulated the expression of HIF-1α and VEGF as compared to ischemia/reperfusion group, while insulin/PEG-b-(PELG-g-PLL) significantly improved this effect. PMID:27175073

  5. miR-208a在大鼠心肌缺血再灌注损伤及缺血后处理中的表达及其作用%Expression and mechanism of miR-208a in rat myocardial ischemia reperfusion injury and ischemic postconditioning

    Institute of Scientific and Technical Information of China (English)

    陈耽; 李骊华

    2015-01-01

    目的:探讨miR-208a及α-肌球蛋白重链(α-myosin heavy chain,a-MHC)、β-肌球蛋白重链(β-myosin heavy chain,β-MHC)在大鼠心肌缺血再灌注损伤(ischemia reperfusion injury,IR)及缺血后处理(ischemic postconditioning,IPO)中的表达变化及其作用.方法:取SD大鼠,使用改良垫扎球囊法建立IR模型,随机分为3组(每组6只),Sham组、IR组、IPO组.检测各组血流动力学指标;real-time PCR检测miR-208a、α-MHC、β-MHC基因表达;Western blot检测α-MHC、β-MHC蛋白含量.结果:与IR组相比,IPO能明显降低左室舒张末期容积(left ventricular end diastolic volume,LVEDV)和左室收缩末期容积(left yen-tricular end systolic volume,LVESV),增加左室射血分数(left ventricular ejection fraction,LVEF)和左室短轴缩短率(left ventricular fraction shorting,LVFS),改善心功能.miR-208a表达水平在IR组明显增加,IPO组明显降低.β-MHC表达在IR组明显上调,IPO组明显下调,且基因和蛋白表达水平一致.α-MHC基因和蛋白表达水平在3组无明显差异.结论:miR-208a和β-MHC在缺血再灌注组明显增加,缺血后处理能使miR-208a和β-MHC表达下降,并在一定程度上改善心功能.%Objective:To observe the expression changes of miR-208a in rat acute myocardium ischemia reperfusion injury (IR) and ischemic postconditioning,to investigate the probable mechanism of miR-208a in the protection of ischemic postconditioning.Methods:Sprague-Dawley rats were randomly assigned into 3 groups:sham operation group,ischemia reperfusion group and ischemic postconditioning group.The hemodynamic values and cardiac function were analyzed by echocardiography.The gene expression of miR-208a,α-MHC,and β-MHC was detected by real-time PCR.Western blot was used to assess the protein expression of α-MHC and β-MHC in the area at risk at the end of reperfusion.Results:Postconditioning in vivo rats reduced the hemodynamic values of left ventricular end diastolic volume (LVEDV

  6. Effect of ischemic preconditioning on the expression of c-myb in the CA1 region of the gerbil hippocampus after ischemia/reperfusion injury

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    Hui Young Lee

    2016-06-01

    Conclusion: Our results show that a lethal transient ischemia significantly decreased c-myb immunoreactivity in the SP of the CA1 region and that IPC well preserved c-myb immunoreactivity in the SP of the CA1 region. We suggest that the maintenance of c-myb might be related with IPC-mediated neuroprotection after a lethal ischemic insult.

  7. Effect of liver ischemic preconditioning in cirrhotic rats submitted to hepatic ischemia/reperfusion injury Efeito do pré-condicionamento isquêmico hepático submetidos a lesão de isquemia/reperfusão do fígado

    Directory of Open Access Journals (Sweden)

    Eduardo Garcia Pacheco

    2006-01-01

    Full Text Available PURPOSE: The main aim of this study was to determine the influence of ischemic preconditioning (IPC on rat liver cirrhosis. METHODS: Cirrhosis was induced in Wistar rats by occlusion of the hepatic duct. The animals were divided into four groups of six animals each: non-cirrhotic group (simulated operation only, cirrhotic control group (simulated operation in cirrhotic rats, I/R group (40-minute ischemia without IPC, and IPC group (cirrhotic rats with ischemia, previously submitted to IPC. The IPC procedure consisted of partial hepatic ischemia for five minutes, followed by 10 minutes of reperfusion. In the case of the IPC group, the animals were submitted to liver ischemia for 40 minutes after the preconditioning procedure, followed by 2 hours of reperfusion. Blood samples were collected for measurement of serum aminotransferases (ALT and AST. The respiratory control ratio (RCR, the mitochondrial membrane potential (MMP, and malondialdehyde (MDA values in the hepatic tissue were analyzed. Nonparametric statistical analysis was used and a value of pOBJETIVO: O objetivo deste estudo foi determinar a influência do pré-condicionamento isquêmico (IPC em fígados de ratos cirróticos. MÉTODOS: A cirrose hepática foi induzida em ratos Wistar machos (250 a 300g por oclusão, durante 30 dias, do ducto hepático comum.A seguir, os animais cirróticos foram divididos em três grupos de seis; Grupo controle cirrótico (operação simulada para isquemia/reperfusão/pré-condicionamento, Grupo I/R, isquemia de 40 minutos sem pré-condicionamento (IPC e grupo IPC com isquemia precedida por IPC. O IPC consistiu de uma isquemia parcial por cinco minutos, seguida por 10 minutos de reperfusão. No grupo IPC, após o pré-condicionamento, os animais foram submetidos à isquemia hepática de 40 minutos seguida de 2 horas de reperfusão. Foram colhidas amostras de sangue para dosagem sérica de aminotransferases (ALT e AST. Razão de controle respiratório (RCR

  8. Remote ischemic preconditioning in cyanosed neonates undergoing cardiopulmonary bypass: a randomized controlled trial.

    Science.gov (United States)

    Jones, Bryn O; Pepe, Salvatore; Sheeran, Freya L; Donath, Susan; Hardy, Pollyanna; Shekerdemian, Lara; Penny, Daniel J; McKenzie, Ian; Horton, Stephen; Brizard, Christian P; d'Udekem, Yves; Konstantinov, Igor E; Cheung, Michael M H

    2013-12-01

    The myocardial protective effect of remote ischemic preconditioning has been demonstrated in heterogeneous groups of patients undergoing cardiac surgery. No studies have examined this technique in neonates. The present study was performed to examine the remote ischemic preconditioning efficacy in this high-risk patient group. A preliminary, randomized, controlled trial was conducted to investigate whether remote ischemic preconditioning in cyanosed neonates undergoing cardiac surgery confers protection against cardiopulmonary bypass. Two groups of neonates undergoing cardiac surgery were recruited for the present study: patients with transposition of the great arteries undergoing the arterial switch procedure and patients with hypoplastic left heart syndrome undergoing the Norwood procedure. The subjects were randomized to the remote ischemic preconditioning or sham control groups. Remote ischemic preconditioning was induced by four 5-minute cycles of lower limb ischemia and reperfusion using a blood pressure cuff. Troponin I and the biomarkers for renal and cerebral injury were measured pre- and postoperatively. A total of 39 neonates were recruited-20 with transposition of the great arteries and 19 with hypoplastic left heart syndrome. Of the 39 neonates, 20 were randomized to remote ischemic preconditioning and 19 to the sham control group. The baseline demographics appeared similar between the randomized groups. The cardiopulmonary bypass and crossclamp times were not significantly different between the 2 groups. The troponin I levels were not significantly different at 6 hours after cardiopulmonary bypass nor were the postoperative inotrope requirements. Markers of renal (neutrophil gelatinase-associated lipocalin) and cerebral injury (S100b, neuron-specific enolase) were not significantly different between the 2 groups. Our data suggest that remote ischemic preconditioning in hypoxic neonates undergoing cardiopulmonary bypass surgery does not provide

  9. Ischemic proximal tubular injury primes mice to endotoxin-induced TNF-alpha generation and systemic release.

    Science.gov (United States)

    Zager, R A; Johnson, Ali C M; Hanson, Sherry Y; Lund, Steve

    2005-08-01

    Endotoxemia (LPS) can exacerbate ischemic tubular injury and acute renal failure (ARF). The present study tested the following hypothesis: that acute ischemic damage sensitizes the kidney to LPS-mediated TNF-alpha generation, a process that can worsen inflammation and cytotoxicity. CD-1 mice underwent 15 min of unilateral renal ischemia. LPS (10 mg/kg iv), or its vehicle, was injected either 45 min before, or 18 h after, the ischemic event. TNF-alpha responses were gauged 2 h post-LPS injection by measuring plasma/renal cortical TNF-alpha and renal cortical TNF-alpha mRNA. Values were contrasted to those obtained in sham-operated mice or in contralateral, nonischemic kidneys. TNF-alpha generation by isolated mouse proximal tubules (PTs), and by cultured proximal tubule (HK-2) cells, in response to hypoxia-reoxygenation (H/R), oxidant stress, antimycin A (AA), or LPS was also assessed. Ischemia-reperfusion (I/R), by itself, did not raise plasma or renal cortical TNF-alpha or its mRNA. However, this same ischemic insult dramatically sensitized mice to LPS-mediated TNF-alpha increases in both plasma and kidney (approximately 2-fold). During late reperfusion, increased TNF-alpha mRNA levels also resulted. PTs generated TNF-alpha in response to injury. Neither AA nor LPS alone induced an HK-2 cell TNF-alpha response. However, when present together, AA+LPS induced approximately two- to fivefold increases in TNF-alpha/TNF-alpha mRNA. We conclude that modest I/R injury, and in vitro HK-2 cell mitochondrial inhibition (AA), can dramatically sensitize the kidney/PTs to LPS-mediated TNF-alpha generation and increases in TNF-alpha mRNA. That ischemia can "prime" tubules to LPS response(s) could have potentially important implications for sepsis syndrome, concomitant renal ischemia, and for the induction of ARF.

  10. Delivery of interleukin-10 via injectable hydrogels improves renal outcomes and reduces systemic inflammation following ischemic acute kidney injury in mice.

    Science.gov (United States)

    Soranno, Danielle E; Rodell, Christopher B; Altmann, Christopher; Duplantis, Jane; Andres-Hernando, Ana; Burdick, Jason A; Faubel, Sarah

    2016-08-01

    Injectable hydrogels can be used to deliver drugs in situ over a sustained period of time. We hypothesized that sustained delivery of interleukin-10 (IL-10) following acute kidney injury (AKI) would mitigate the local and systemic proinflammatory cascade induced by AKI and reduce subsequent fibrosis. Wild-type C57BL/6 mice underwent ischemia-reperfusion AKI with avertin anesthesia. Three days later, mice were treated with either hyaluronic acid injectable hydrogel with or without IL-10, or IL-10 suspended in saline, injected under the capsule of the left kidney, or hydrogel with IL-10 injected subcutaneously. Untreated AKI served as controls. Serial in vivo optical imaging tracked the location and degradation of the hydrogel over time. Kidney function was assessed serially. Animals were killed 28 days following AKI and the following were evaluated: serum IL-6, lung inflammation, urine neutrophil gelatinase-associated lipocalin, and renal histology for fibroblast activity, collagen type III deposition and fibrosis via Picrosirius Red staining and second harmonic imaging. Our model shows persistent systemic inflammation, and renal inflammation and fibrosis 28 days following AKI. The hydrogels are biocompatible and reduced serum IL-6 and renal collagen type III 28 days following AKI even when delivered without IL-10. Treatment with IL-10 reduced renal and systemic inflammation, regardless of whether the IL-10 was delivered in a sustained manner via the injectable hydrogel under the left kidney capsule, as a bolus injection via saline under the left kidney capsule, or via the injectable hydrogel subcutaneously. Injectable hydrogels are suitable for local drug delivery following renal injury, are biocompatible, and help mitigate local and systemic inflammation. Copyright © 2016 the American Physiological Society.

  11. Protection of retinal function by sulforaphane following retinal ischemic injury.

    Science.gov (United States)

    Ambrecht, Lindsay A; Perlman, Jay I; McDonnell, James F; Zhai, Yougang; Qiao, Liang; Bu, Ping

    2015-09-01

    Sulforaphane, a precursor of glucosinolate in cruciferous vegetables such as broccoli and cauliflower, has been shown to protect brain ischemic injury. In this study, we examined the effect of systemic administration of sulforaphane on retinal ischemic reperfusion injury. Intraocular pressure was elevated in two groups of C57BL/6 mice (n = 8 per group) for 45 min to induce retinal ischemic reperfusion injury. Following retinal ischemic reperfusion injury, vehicle (1% DMSO saline) or sulforaphane (25 mg/kg/day) was administered intraperitoneally daily for 5 days. Scotopic electroretinography (ERG) was used to quantify retinal function prior to and one-week after retinal ischemic insult. Retinal morphology was examined one week after ischemic insult. Following ischemic reperfusion injury, ERG a- and b-wave amplitudes were significantly reduced in the control mice. Sulforaphane treatment significantly attenuated ischemic-induced loss of retinal function as compared to vehicle treated mice. In vehicle treated mice, ischemic reperfusion injury produced marked thinning of the inner retinal layers, but the thinning of the inner retinal layers appeared significantly less with sulforaphane treatment. Thus, sulforaphane may be beneficial in the treatment of retinal disorders with ischemic reperfusion injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Pre-treatment with radix astragali for myocardial cell apoptosis and its relative genes in rats with ischemic reperfusion%黄芪预处理对缺血再灌注大鼠心肌细胞凋亡及相关基因的影响

    Institute of Scientific and Technical Information of China (English)

    赵淑敏; 韩莉; 马立辉; 周健; 孔祥玉

    2005-01-01

    BACKGROUND: Radix astragali has the effect of protecting cells from damage in ischemic reperfusion, whether pre-treatment with radix astragali can protect myocardial eells from apoptosis in ischemic reperfusion ? OBJECTIVE: To investigate the effect of pre-treatment with radix astragali on apoptosis and its relative genes in rats with ischemic myocardial reperfusion DESIGN: A randomized and controlled trial taking Wistar rats as experimental subjects.SETTING: The Basic Medical Department of Chengde Medical College and the Geriatric Department of the Affiliated Hospital.MATERIALS: The experiment was completed in the Imunnohistochemical Laboratory of Basic Medical Institute in Chengde Medical College from February to December in 2004. A total of 30 healthy male Wistar rats were selected, and at random classified as groups of radix astragali pre-treated (radix astragali), ischemic reperfusion and psuedo-operated (control), 10 rats for each group.METHODS: Radix astragali injection was given peritonealy for rats in radix astragali pre-treated group before operation, and the equivalent normai saline was given for those in ischemic reperfusion and psuedo-operated groups. One week later, the model of ischemic reperfusion was set up. After operation the myocardia in marginal zone of ischemic reperfusion were sampled, and the myocardia of the corresponding zone were taken for control group. The method of terminal (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) was used for assay of myocardial apoptosis rate, and the ABC immunohistochemical method was used for assay of myocardial bcl-2 (inhibiting apoptosis gene) and bax (promoting apoptosis gene).MAIN OUTCOME MEASURES: Apoptosis rates, and expression of bcl2 and bax genes of myocardia RESULTS: ① Apoptosis rate of myocardial cells: The rate in radix astragali group was decreased compared with that in ischemic reperfusion group [ (14.06 ±9.97) %, (19.34±12.30) %, t = 1.863, P < 0.05].② Expression of bcl-2

  13. Heart Rate Variability in Patients with Acute Ischemic Stroke at Different Stages of Renal Dysfunction: A Cross-sectional Observational Study

    Science.gov (United States)

    Wei, Lin; Zhao, Wen-Bo; Ye, Huan-Wen; Chen, Yan-Hua; Zhang, Xiao-Pei; Huang, Yan; Cai, Ye-Feng; Chen, Quan-Fu; Pan, Su-Yue

    2017-01-01

    Background: Renal function is associated with mortality and functional disabilities in stroke patients, and impaired autonomic function is common in stroke, but little is known regarding its effects on stroke patients with renal dysfunction. This study sought to evaluate the association between autonomic function and stroke in patients with renal dysfunction. Methods: This study comprised 232 patients with acute ischemic stroke consecutively enrolled from February 2013 to November 2014 at Guangdong Provincial Hospital of Chinese Medicine in China. All patients recruited underwent laboratory evaluation and 24 h Holter electrocardiography (ECG). Autonomic function was measured based on the heart rate variability (HRV) using 24 h Holter ECG. Renal damage was assessed through the estimated glomerular filtration rate (eGFR), and stroke severity was rated according to the National Institutes of Health Stroke Scale (NIHSS). The Barthel index and modified Rankin score were also determined following admission. All the clinical covariates that could potentially affect autonomic outcome variables were adjusted with linear regression. Results: In the patients with a mild or moderate decreased eGFR, the values for the standard deviation of the averaged normal-to-normal RR interval (SDANN) index (P = 0.022), very low frequency (VLF) (P = 0.043), low frequency (LF) (P = 0.023), and ratio of low-to-high frequency power (LF/HF) (P = 0.001) were significantly lower than those in the patients with a normal eGFR. A multinomial linear regression indicated that eGFR (t = 2.47, P = 0.014), gender (t = −3.60, P < 0.001), and a history of hypertension (t = −2.65, P = 0.008) were the risk factors of LF/HF; the NIHSS score (SDANN index: t = −3.83, P < 0.001; VLF: t = −3.07, P = 0.002; LF: t = −2.79, P = 0.006) and a history of diabetes (SDANN index: t = −3.58, P < 0.001; VLF: t = −2.54, P = 0.012; LF: t = −2.87, P = 0.004) were independent factors for the SDANN index, VLF

  14. Comparison of the fat elimination between long-chain triglycerides and medium-chain triglycerides in rats with ischemic acute renal failure.

    Science.gov (United States)

    Ge, Yuqiang; Xu, Yuanzhao; Liao, Lutan

    2002-01-01

    To guide the administration of fat emulsion in the nutritional support of acute renal failure (ARF), pharmacokinetic analysis with an one-compartment open model after bolus intravenous injection was performed to compare the elimination kinetics of long-chain triglycerides (LCT) and medium-chain triglycerides (MCT) in ischemic acute renal failure rats. Sprague-Dawley rats were randomized into four groups, namely LCT normal group, LCT ARF group, MCT normal group and MCT ARF group. The model of ischemic acute renal failure was induced by clamping the left renal artery for 60 min and contralateral nephrectomy. All the rats were fasted with water ad libitum for 10 h before 0.3 g/kg body weight of 10% Intralipid (LCT) or 10% Lipofundin (MCT: LCT = 50:50) was injected as a bolus to them via the tail vein. The serum triglyceride concentration was determined at 2, 10, 40, 70, 100, 130 and 160 min after intravenous injection for kinetic analysis. The results showed that the elimination rate constant (ke) of LCT ARF group was significantly decreased, while the half life period (t1/2) of it was significantly longer than those of LCT normal group. The ke and t1/2 of MCT showed no statistical difference between normal and ARF groups. In the normal group the ke of LCT was significantly decreased compared with MCT whereas the t1/2 was significantly prolonged. In the ARF group the ke of LCT was much less than that of MCT while the t1/2 was much longer. The serum insulin levels of both MCT groups were significantly higher than those of LCT groups. These results indicate that MCT will be eliminated more rapidly than LCT in ARF rats. MCT may also increase the secretion of insulin. In conclusion, MCT may be more favorable than LCT in the nutritional management of ARF.

  15. Interfering effect of neuregulin upon cerebral ischemic reperfusion injury in rhesus monkeys%神经调节素对猕猴脑缺血再灌注损伤的干预作用

    Institute of Scientific and Technical Information of China (English)

    张睿; 李琴; 王涛; 杜芳; 郭云良

    2009-01-01

    Objective To study the interfering effect of neuregulin-1β(NRG-1β)on the cerebral ischemic reperfusion injury in monkeys.Methods The models with middle cerebral artery occlusion reperfusion (MCAO/R) were established by inserting a micro-balloon catheter intra-arterially into MCA from femoral artery in 12 adult healthy monkeys. The NRG-1β was injected into MCA from micro-balloon catheter in the animals of treatment group at 2 h post-ischemia while the normal saline was simultaneously injected in the animals of control group. Then the micro-balloon catheter was withdrawn from the MCA to perfuse for 22 h. The nervous behavioral function was evaluated by task-oriented score and the infarct volume measured by TTC and MRI.Results The animals of control group had an onset of nervous functional disorders at 2 h post-ischemia and had no significant difference at reperfusion 22 h (59.8±15.7); the nervous function of monkeys had no improvement after NFG-1β treatment (61.3±16.2) (P>0.05). The diffuse weight imaging (DWI) showed a high signal area but T1 and T2 imaging had no significant changes at 2 h post-ischemia in control group animals; while the T1 and T2 imaging showed a typical high signal areas, DWI high signal area expanded and TTC staining ischemic area appeared at reperfusion 22 h. The T1, T2 and DWI abnormal signal areas and TTC cerebral infarct volume did not shrink significantly in NFG-1β treatment group (P>0.05).Conclusion The neuroprotective effects of NRG-1β upon cerebral ischemic reperfusion injury needs to be further studied.%目的 探讨神经调节素-1β(NRG-1β)对猕猴脑缺血再灌注损伤的保护作用.方法 成年健康猕猴12只,经股动脉介入手术,将微球囊导管插入大脑中动脉阻断其血流,建立大脑中动脉缺血再灌注(MCAO/R)模型.治疗组动物于缺血2 h再灌注前经微球囊导管注射NRG-1β,对照组同步给予等量的生理盐水,然后退出微球囊导管实现再灌注22 h.应用Task

  16. The anti-oxidative role of micro-vesicles derived from human Wharton-Jelly mesenchymal stromal cells through NOX2/gp91(phox suppression in alleviating renal ischemia-reperfusion injury in rats.

    Directory of Open Access Journals (Sweden)

    Guangyuan Zhang

    Full Text Available Oxidative stress is known as one of the main contributors in renal ischemia/reperfusion injury (IRI. Here we hypothesized that Micro-vesicles (MVs derived from human Wharton Jelly mesenchymal stromal cells (hWJMSCs could protect kidney against IRI through mitigating oxidative stress. MVs isolated from hWJMSCs conditioned medium were injected intravenously in rats immediately after unilateral kidney ischemia for 60 min. The animals were sacrificed at 24 h, 48 h and 2 weeks respectively after reperfusion. Our results show that the expression of NOX2 and reactive oxygen species (ROS in injured kidney tissues was declined and the oxidative stress was alleviated in MVs group at 24 h and 48 h in parallel with the reduced apoptosis and enhanced proliferation of cells. IRI-initiated fibrosis was abrogated by MVs coincident with renal function amelioration at 2 weeks. NOX2 was also found down-regulated by MVs both in human umbilical vein endothelial cells (HUVEC and NRK-52E cell line under hypoxia injury model in vitro. In conclusion, a single administration of hWJMSC-MVs might protect the kidney by alleviation of the oxidative stress in the early stage of kidney IRI through suppressing NOX2 expression. Moreover, it could reduce the fibrosis and improved renal function.

  17. Remifentanil-induced preconditioning has cross-talk with A1 and A2B adenosine receptors in ischemic-reperfused rat heart

    Directory of Open Access Journals (Sweden)

    Yong-Cheol Lee

    2016-01-01

    Full Text Available The purpose of this study was to determine whether there is a cross-talk between opioid receptors (OPRs and adenosine receptors (ADRs in remifentanil preconditioning (R-Pre and, if so, to investigate the types of ADRs involved in the cross-talk. Isolated rat hearts received 30 min of regional ischemia followed by 2 hr of reperfusion. OPR and ADR antagonists were perfused from 10 min before R-Pre until the end of R-Pre. The heart rate, left ventricular developed pressure (LVDP,velocity of contraction (+dP/dtmax, and coronary flow (CF were recorded. The area at risk and area of necrosis were measured. After reperfusion, the LVDP, +dP/dtmax,and CF showed a significant increase in the R-Pre group compared with the control group (no intervention before or after regional ischemia. These increases in the R-Pre group were blocked by naloxone, a nonspecific ADR antagonist, an A1 ADR antagonist, and an A2B ADR antagonist. The infarct size was reduced significantly in the R-Pre group compared with the control group. The infarct-reducing effect in the R-Pre group was blocked by naloxone, the nonspecific ADR antagonist, the A1 ADR antagonist, and the A2B ADR antagonist. The results of this study demonstrate that there is cross-talk between ADRs and OPRs in R-Pre and that A1 ADR and A2B ADR appear to be involved in the cross-talk.

  18. 替普瑞酮对大鼠肾脏缺血再灌注损伤的保护作用%Geranylgeranylacetone attenuates renal ischemia reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    张白玉; 毛海萍; 陈崴; 李志坚; 李志莲; 安欣; 余学清

    2008-01-01

    目的 探讨替普瑞酮对肾脏缺血再灌注损伤的保护作用和可能机制.方法 应用替普瑞酮(400 mg/kg)诱导雄性SD大鼠肾脏高表达热休克蛋白72(HSP72).以钳夹大鼠左肾蒂45 min后,松开血管夹并切除右肾,建立大鼠缺血再灌注肾脏损伤模型.假手术组为打开腹腔,分离肾血管周围组织,但不钳夹血管.模型建立后24 h处死大鼠,留取血清测血肌酐(Ser)和尿素氮(BUN).肾组织石蜡切片行PAS染色,以损伤肾小管所占百分比评分法评估肾组织肾小管损伤程度.TUNEL法检测缺血再灌注损伤时肾脏细胞凋亡的发生情况.Western印迹检测X连锁凋亡抑制蛋白(XIAP)的水平.结果 缺血再灌注损伤可导致急性肾衰竭,表现为血Scr、BUN明显升高(P<0.01);PAS染色显示外髓部有大片肾小管坏死,甚至出现基底膜裸露;TUNEL染色中肾小管上皮细胞TUNEL阳性细胞数明显增多(P<0.01);Western印迹结果显示,肾组织XIAP蛋白水平明显降低(P<0.01).替普瑞酮处理后,肾组织HSP72表达水平明显增高(P<0.01);缺血再灌注所致的肾脏损伤明显改善,包括肾小管的损伤、细胞凋亡以及肾功能.此外,替普瑞酮可稳定肾组织XIAP的蛋白水平(P<0.05).结论 替普瑞酮可诱导肾脏高表达HSP72.替普瑞酮可能通过减少肾脏XIAP蛋白的降解,抑制细胞凋亡,减轻缺血再灌注的肾脏损伤.%Objective To explore the protective effects of geranylgeranylacetone (GGA) on acute renal failure tats induced by isehemia reperfusion (IR) and the possible mechanism. Methods GGA (400 mg/kg) was administered to induce overexpression of heat shock protein 72 (HSP72) in the kidney of Sprague-Dawley (SD) rats. IR model was generated by temporary clamping the left renal artery for 45 minutes followed by right nephrectomy and 24 h reperfusion. A sham-operated group was used as normal control. 24 h after reperfnsion, rats were sacrificed. Blood was collected for measurement of

  19. The effect of insulin-loaded linear poly(ethylene glycol)-brush-like poly(l-lysine) block copolymer on renal ischemia/reperfusion-induced lung injury through downregulating hypoxia-inducible factor

    OpenAIRE

    Tong F; Tang XY; Li X.; Xia WQ; Liu DJ

    2016-01-01

    Fei Tong, Xiangyuan Tang, Xin Li, Wenquan Xia, Daojun Liu Department of Chemistry, Medical College, Shantou University, Shantou, People’s Republic of China Abstract: The aim of this study was to observe the therapeutic effect of insulin-loaded linear poly(ethylene glycol)-brush-like poly(L-lysine) block copolymer poly(ethylene glycol)-b-(poly(ethylenediamine L-glutamate)-g-poly(L-lysine)) (PEG-b-(PELG-g-PLL) on renal ischemia/reperfusion-induced lung injury through downregulating ...

  20. High temporal resolution parametric MRI monitoring of the initial ischemia/reperfusion phase in experimental acute kidney injury.

    Science.gov (United States)

    Pohlmann, Andreas; Hentschel, Jan; Fechner, Mandy; Hoff, Uwe; Bubalo, Gordana; Arakelyan, Karen; Cantow, Kathleen; Seeliger, Erdmann; Flemming, Bert; Waiczies, Helmar; Waiczies, Sonia; Schunck, Wolf-Hagen; Dragun, Duska; Niendorf, Thoralf

    2013-01-01

    Ischemia/reperfusion (I/R) injury, a consequence of kidney hypoperfusion or temporary interruption of blood flow is a common cause of acute kidney injury (AKI). There is an unmet need to better understand the mechanisms operative during the initial phase of ischemic AKI. Non-invasive in vivo parametric magnetic resonance imaging (MRI) may elucidate spatio-temporal pathophysiological changes in the kidney by monitoring the MR relaxation parameters T2* and T2, which are known to be sensitive to blood oxygenation. The aim of our study was to establish the technical feasibility of fast continuous T2*/T2 mapping throughout renal I/R. MRI was combined with a remotely controlled I/R model and a segmentation model based semi-automated quantitative analysis. This technique enabled the detailed assessment of in vivo changes in all kidney regions during ischemia and early reperfusion. Significant changes in T2* and T2 were observed shortly after induction of renal ischemia and during the initial reperfusion phase. Our study demonstrated for the first time that continuous and high temporal resolution parametric MRI is feasible for in-vivo monitoring and characterization of I/R induced AKI in rats. This technique may help in the identification of the timeline of key events responsible for development of renal damage in hypoperfusion-induced AKI.

  1. High temporal resolution parametric MRI monitoring of the initial ischemia/reperfusion phase in experimental acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Andreas Pohlmann

    Full Text Available Ischemia/reperfusion (I/R injury, a consequence of kidney hypoperfusion or temporary interruption of blood flow is a common cause of acute kidney injury (AKI. There is an unmet need to better understand the mechanisms operative during the initial phase of ischemic AKI. Non-invasive in vivo parametric magnetic resonance imaging (MRI may elucidate spatio-temporal pathophysiological changes in the kidney by monitoring the MR relaxation parameters T2* and T2, which are known to be sensitive to blood oxygenation. The aim of our study was to establish the technical feasibility of fast continuous T2*/T2 mapping throughout renal I/R. MRI was combined with a remotely controlled I/R model and a segmentation model based semi-automated quantitative analysis. This technique enabled the detailed assessment of in vivo changes in all kidney regions during ischemia and early reperfusion. Significant changes in T2* and T2 were observed shortly after induction of renal ischemia and during the initial reperfusion phase. Our study demonstrated for the first time that continuous and high temporal resolution parametric MRI is feasible for in-vivo monitoring and characterization of I/R induced AKI in rats. This technique may help in the identification of the timeline of key events responsible for development of renal damage in hypoperfusion-induced AKI.

  2. Effects of supplementing qi and activating blood circulation on piamatral microcirculation in gerbils with cerebral ischemic reperfusion%益气活血对脑缺血再灌注沙土鼠脑膜微循环的作用

    Institute of Scientific and Technical Information of China (English)

    俞国平; 戴良珏; 方敏; 谢荭

    2006-01-01

    通,红细胞中度聚集,白细胞数多,有时可见白色微小血栓,微血管周围渗出现象无明显改观.药物组经腹腔注射益气活血药后,细动、静脉开放,血液速度加快,血流量明显增加,细静脉沉积物开始减少,血栓凝块逐渐疏松,栓塞处疏通,红细胞呈轻度聚集或正常,缺血区血供较再灌流后进一步改善,微血管周围渗出现象逐渐减轻甚至消退.对照组未见明显改变.②药物组动物细动脉流速1.04~1.50 mm/s,明显高于对照组,差异有显著性意义(P<0.05~0.01).③药物组动物细静脉流速0.96~1.12 mm/s,明显高于对照组,差异有显著性意义(P<0.05~0.01).结论:益气活血法对沙土鼠脑缺血再灌注后脑膜微循环的作用确切,其直接作用与加快血流速度,扩张细动脉、细静脉管径,改善大脑血供等有关.%BACKGROUND: The key point in the treatment of acute cerebral infarction lies in inproving the blood supply of brain effectively as soon as possible as well as rescue ischemic and half diazonal nerve cells, so as to contract the local of infarction as great as possible.OBJECTIVE: To observe the effect of traditional treatment of cerebral piamatral microcirculation in gerbil with cerebral ischemic reperfusion injury by supplementing qi and activating blood circulation.DESIGN: Contrast animal experiment at random.SETTING: Zhabei Branch of Shanghai Changzheng Hospital.MATERIALS: The experiment was performed in the Institute of Naval Medicine (key laboratory of the whole army). Twenty-two healthy Monglian gerbils of clean grade (six months old) were selected and randomly divided into medicine group and control group with 11 gerbils in each group.METHODS: Animals were routinely anaesthetized and fixed in prone position to open the cranium window in median line and expose the pia mater. The cranium window was protected by being covered with a cotton ball containing artificial cerebrospinal fluid (ACSF) after operation. Gerbils were fixed in dorsal

  3. Prevention of grafted liver from reperfusive injury

    Institute of Scientific and Technical Information of China (English)

    Kai Ma; Yang yu; Xian-Min Bu; Yan-Jun Li; Xian-Wei Dai; Liang Wang; Yang Dai; Hai-Ying Zhao; Xiang-Hong Yang

    2001-01-01

    @@ INTRODUCTIONThe incidence of primary non-function(PNF)of grafted liver in the early postoperative stage is 2%-23%[1-4],its main cause is the ischemic-rechemic injure[5,6].In this experiment,anisodamine was added into the preserving fluid and the grafted liver was rewarmed at different temperatures to protect the cell membranc and prevent ischemic-reperfusive injury.

  4. The effect of insulin-loaded linear poly(ethylene glycol-brush-like poly(L-lysine block copolymer on renal ischemia/reperfusion-induced lung injury through downregulating hypoxia-inducible factor

    Directory of Open Access Journals (Sweden)

    Tong F

    2016-04-01

    Full Text Available Fei Tong, Xiangyuan Tang, Xin Li, Wenquan Xia, Daojun Liu Department of Chemistry, Medical College, Shantou University, Shantou, People’s Republic of China Abstract: The aim of this study was to observe the therapeutic effect of insulin-loaded linear poly(ethylene glycol-brush-like poly(L-lysine block copolymer poly(ethylene glycol-b-(poly(ethylenediamine L-glutamate-g-poly(L-lysine (PEG-b-(PELG-g-PLL on renal ischemia/reperfusion-induced lung injury through downregulating hypoxia-inducible factor (HIF as compared to free insulin. Sprague Dawley rats were pretreated with 30 U/kg insulin or insulin/PEG-b-(PELG-g-PLL complex, and then subjected to 45 minutes of ischemia and 24 hours of reperfusion. The blood and lungs were collected, the level of serum creatinine and blood urea nitrogen were measured, and the dry/wet lung ratios, the activity of superoxide dismutase and myeloperoxidase, the content of methane dicarboxylic aldehyde and tumor necrosis factor-α, and the expression of HIF-1α and vascular endothelial growth factor (VEGF were measured in pulmonary tissues. Both insulin and insulin/PEG-b-(PELG-g-PLL preconditioning improved the recovery of renal function, reduced pulmonary oxidative stress injury, restrained inflammatory damage, and downregulated the expression of HIF-1α and VEGF as compared to ischemia/reperfusion group, while insulin/PEG-b-(PELG-g-PLL significantly improved this effect. Keywords: insulin, block copolymer, RI/RILI, HIF-1α, VEGF

  5. Transient ureteral obstruction prevents against kidney ischemia/reperfusion injury via hypoxia-inducible factor (HIF-2α activation.

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    Shun Zhang

    Full Text Available Although the protective effect of transient ureteral obstruction (UO prior to ischemia on subsequent renal ischemia/reperfusion (I/R injury has been documented, the underlying molecular mechanism remains to be understood. We showed in the current study that 24 h of UO led to renal tubular hypoxia in the ipsilateral kidney in mice, with the accumulation of hypoxia-inducible factor (HIF-2α, which lasted for a week after the release of UO. To address the functions of HIF-2α in UO-mediated protection of renal IRI, we utilized the Mx-Cre/loxP recombination system to knock out target genes. Inactivation of HIF-2α, but not HIF-1α blunted the renal protective effects of UO, as demonstrated by much higher serum creatinine level and severer histological damage. UO failed to prevent postischemic neutrophil infiltration and apoptosis induction in HIF-2α knockout mice, which also diminished the postobstructive up-regulation of the protective molecule, heat shock protein (HSP-27. The renal protective effects of UO were associated with the improvement of the postischemic recovery of intra-renal microvascular blood flow, which was also dependent on the activation of HIF-2α. Our results demonstrated that UO protected the kidney via activation of HIF-2α, which reduced tubular damages via preservation of adequate renal microvascular perfusion after ischemia. Thus, preconditional HIF-2α activation might serve as a novel therapeutic strategy for the treatment of ischemic acute renal failure.

  6. Influences of ischemic preconditioning on autophagy in rats with cerebral ischemia reperfusion injury%缺血预处理对大鼠脑缺血再灌注自噬的影响

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    石秋艳; 刘冰; 张春阳; 范亚霞; 孙原; 杨斌

    2014-01-01

    Objective To observe the effect of ischemic preconditioning ( IPC) effect on cerebral ischemia reperfusion in rat hippocampus of autophagy .Methods According to method of Zea-Longa filamene , rats middle cerebral artery ischemi-a-reperfusion model were established , the experimental animal were randomly divided into 3 groups: sham operation group (Sham group, n =10), ischemia reperfusion group (I/R group, n =10), IPC treatment group (IPC group, n =30), in IPC group, according to ischemic preconditioning time , rats were divided into 1 d, 3 d, 5 d subgroups, 10 rats in each group.Af-ter ischemia 2 h and reperfusion 24 h, immunohistochemical method was used to detect the autophagy associated protein BEC -LIN L, LC3-II expression, transmission electron microscope in nerve cell autophagy and lysosomal activation and cell ultra -structure changes .Results ( 1 ) Neurological dysfunction score: compared with Sham group , I/R group and IPC group showed varying degrees of nerve dysfunction ( P <0.01), I/R group of symptoms in IPC subgroups ( P <0.05).(2) The volume of cerebral infarction:compared with Sham group , I/R group and IPC group had different degree of infarction ( P <0.01);IPC group was lower than that in I/R group ( P <0.01), 3 d subgroup was less than 1 d and 5 d subgroup ( P <0.01).(3) Immunohistochemical staining:compared with Sham group , I/R group and IPC group, the number of BECLIN 1 and LC3-II positive cells ( P <0.01), the expression of IPC positive cells was significantly lower than that of I /R group (P <0.01), IPC 3 d subgroup was less than 1 d, 5 d subgroup ( P <0.01).(4) The change of brain tissue ultrastructure morphology of cells:Sham group was normal;I/R group and IPC group showed varying amounts of autophagy , in different peri-od and or autophagic lysosome , mitochondria swelling, rupture of membranes, vesicles, lysosomes increased significantly ,visi-ble deformation of secondary lysosomes ,Golgi fragmentation;IPC group autophagy and the number

  7. Plausible mechanism of antioxidant action of Fagonia cretica linn, Rubia cordifolia and Tinospora cordifolia during ischemic reperfusion injury in rat hippocampus

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    A K Rawal

    2008-06-01

    Full Text Available Summary: Reactive oxygen species (ROS and nitrogen species (RNS have been implicated in a wide variety of diseases including cerebral ischemic neuronal damage. We have earlier demonstrated the antioxidant and anti-inflammatory properties of the herbs Rubia cordifolia (RC, Fagonia cretia linn (FC and Tinospora cordifolia (TC in rat hippocampal slices subjected to oxygen glucose deprivation (OGD. In this communication we have hypothesized that the herbs exert their antioxidant action by both, direct scavenging and decreased generation of superoxide, nitric oxide, peroxynitrite and hydroxyl free radicals. Treatment of OGD slices with RC, FC or TC significantly reduced the generation of the aforesaid radicals, nitric oxide synthase activity and increased Cu-Zn superoxide dismutase (Cu-Zn SOD enzyme levels in the cytosol. The herbs markedly inhibited inducible nitric oxide synthase (iNOS gene expression and up-regulated the expression of Cu-Zn SOD gene. Studies with electron paramagnetic resonance (EPR and ion selective electrode for nitric oxide radical have revealed that the herbs could directly scavenge the free radicals. Overall the three herbs modulated free radical generation both at the cytosolic as well as at the nuclear levels.   Industrial relevance: Reactive oxygen species (ROS and nitrogen species (RNS have been implicated in a wide variety of diseases including cerebral ischemic neuronal damage. Currently there is a race for discovering new and more effective and efficient antioxidants and anti-inflammatory molecules. However, most synthetic molecules have undesired side effects and therefore have proved to be deleterious to health in the long run. The present study aims at investigating whether or not RC, TC and FC have antioxidant properties and if they have, what is the mechanism of their action. Such an investigation will lead to the identification, purification and characterization of the antioxidant molecule(s in the said herbs

  8. Effects of ischemic postconditioning on myocardial apoptosis and infarction in rabbits with acute myocardial ischemia and reperfusion%缺血后处理对缺血再灌注大鼠心肌梗死和心肌细胞凋亡的作用

    Institute of Scientific and Technical Information of China (English)

    李源; 陶凌; 臧益民; 高峰

    2002-01-01

    AIM To observe the effects of ischemic postconditioning (IPC) on cardiomyocyte apoptosis and myocardial infarct size in myocardial ischemia/reperfusion rabbits. METHODS Rabbit acute myocardial ischemia/reperfusion model was used and the heart was conditioned either pre-or post-myocardial ischemia followed by reperfusion. Cardiomyocyte apoptosis and myocardial infarct size were determined by in situ TDT-mediated dUTP nick end labeling (TUNEL) and Evan's blue-TTC dual staining, respectively. RESULTS Compared with those in the control group, both cardiomyocyte apoptotic index and myocardial infarct size were significantly reduced in IPC group [apoptotic index: (15±7)% vs (30±12)% of control, P<0.05; infarction:(13±5)% vs (27±7)% of control, P<0.01, respectively]. No significant difference was found between ischemic preconditioning (IP) and IPC groups. CONCLUSION Ischemic postconditioning, like ischemic preconditioning, exerts an anti-apoptotic effect, which may contribute partly to the ultimate reduction of myocardial infarction in acute myocardial ischemia-reperfusion.%目的观察在体情况下缺血后处理(IPC)对兔心肌梗死范围及缺血心肌细胞凋亡的影响,并与缺血预处理(IP)心脏保护作用比较. 方法采用兔心肌缺血/再灌注模型,在缺血后、再灌注前多次短暂再灌/停灌处理. 以Even's blue-TTC法检测心肌梗死范围,TUNEL方法检测缺血心肌细胞凋亡. 结果与对照组相比,缺血后处理明显减小心肌梗死范围(12.5±5.4% vs对照组26.7±6.7%, P<0.01),缺血区心肌凋亡指数明显下降(14.6±7.4 vs对照组30.4±12.3, P<0.05). 结论对于已缺血心肌,再灌前予多次短暂复灌、停灌处理具有与IP类似缩小心梗范围作用,IPC对缺血心肌的保护效应可能与其抑制缺血心肌细胞凋亡有关.

  9. 一种新型实用的大鼠肾缺血再灌注损伤模型的建立%Model construction of renal ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    余晓东; 程树林; 廖波; 邓显忠; 姜果; 朱平宇; 鲁栋梁; 唐铁龙; 杨雪松; 陈双全

    2011-01-01

    Objective To construct a simple and practical model of renal ischemia-reperfusion injury in rats.Methods 48 male Sprague-Dawley rats were randomly divided into two groups : control group(C group) and ischemiareperfusion group(IK group) ,the four phases (6,12,24 , 72 h) in each group.At 45 min after the left renal artery occlusion on the basis of the right renal resection,we restored perfusion in modeling of ischemia-reperfusion injury.To determine serum creatinine ( Scr) and to observe renal histological and ultrastructural changes.Results After ischemiareperfusion, the level of serum creatinine (Scr) was increased significantly,the morphology and ultrastructure of renal tissue were damaged significantly, which indicating that the construction of animal model was successful.Conclusion Using the technique to construct renal ischemiareperfusion rat model is simple and practical.%目的 建立一种简单实用的大鼠肾缺血再灌注损伤模型.方法 48只雄性SD大鼠随机分成2组:对照组(C组)、缺血再灌注组(Ir组),每组各4个时相(6、12、24、72 h).采用切除右肾,夹闭左肾动脉45 min后恢复灌流建立缺血再灌注损伤模型.检测血清肌酐(Scr)水平,观察肾组织病理学改变及超微结构变化.结果 缺血再灌注后,Scr水平显著升高,肾组织形态学和超微结构出现明显的损伤和破坏,表明动物模型建立成功.结论 该方法 建立大鼠肾缺血再灌注损伤模型简单实用.

  10. Effect of thymoquinone on hepatic ischemic-reperfusion injury%百里醌对肝缺血-再灌注损伤的作用研究

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    朱蕾; 张丽

    2016-01-01

    Objective To investigate the effect and mechanism of thymoquinone on hepatic ischemia-reperfusion injury (IRI).Methods Thirty C57 mice were randomly divided into the sham operation (sham),IRI and thymoquinone (Thy)groups (n =1 0 in each group).At preoperative 1 h,thymoquinone at a dose of 40 ml/kg was administered via intraperitoneal injection in the Thy group.Absolute ethyl alcohol at the same dosage was given via intraperitoneal injection in the sham and IRI groups.Liver IRI mouse models were established in the IRI and Thy groups.Serum and liver specimens were collected at 4 h after reperfusion.Under light microscope,hepatic histopathological changes were observed and assessed by pathological injury grading.Reverse transcription polymerase chain reaction (RT-PCR)was performed to measure the messenger ribonucleic acid (mRNA)expression levels of tumor necrosis factor (TNF)-α,monocyte chemotactic protein (MCP)-1 and interleukin (IL)-6.The expression of TNF-α,MCP-1 and IL-6 proteins in the serum in the serum were assessed by ELISA.The content of malondialdehyde (MDA)in the liver tissue was detected by thiobarbituric acid (TBA).The activity of catalase (CAT),glutathioneperoxidase (GPx)and superoxide dismutase (SOD)in the liver tissue was determined by ELISA.The expression levels of Wnt,β-catenin and p53 proteins were measured by Western blot.Results Compared with the sham group,the liver injury was more severe and the hepatic injury grading was significantly enhanced in the IRI group (P <0.05),the expression of TNF-α,MCP-1 and IL-6 in the liver tissue and serum sample,and MDA, Wnt,β-catenin and p53 in the liver tissue was significantly up-regulated (P <0.05-0.001 ),whereas CAT,GPx and SOD activity in the liver tissue was dramatically reduced (all in P <0.001 ).Compared with the IRI group,the liver injury in the Thy group was slighter and the liver injury grading was significantly decreased (both in P <0.05).The expression levels of TNF-α,MCP-1 and IL-6 in the

  11. Cardioprotection by remote ischemic conditioning: Mechanisms and clinical evidences

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    Alberto; Aimo; Chiara; Borrelli; Alberto; Giannoni; Luigi; Emilio; Pastormerlo; Andrea; Barison; Gianluca; Mirizzi; Michele; Emdin; Claudio; Passino

    2015-01-01

    In remote ischemic conditioning(RIC), several cycles of ischemia and reperfusion render distant organ and tissues more resistant to the ischemia-reperfusion injury. The intermittent ischemia can be applied before the ischemic insult in the target site(remote ischemic preconditioning), during the ischemic insult(remote ischemic perconditioning) or at the onset of reperfusion(remote ischemic postconditioning). The mechanisms of RIC have not been completely defined yet; however, these mechanisms must be represented by the release of humoral mediators and/or the activation of a neural reflex. RIC has been discovered in the heart, and has been arising great enthusiasm in the cardiovascular field. Its efficacy has been evaluated in many clinical trials, which provided controversial results. Our incomplete comprehension of the mechanisms underlying the RIC could be impairing the design of clinical trials and the interpretation of their results. In the present review we summarize current knowledge about RIC pathophysiology and the data about its cardioprotective efficacy.

  12. Prevention of renal ischemia/reperfusion injury in rats using acetylcysteine after anesthesia with isoflurane Prevenção de lesão de isquemia/reperfusão em ratos com acetilcisteína após anestesia com isoflurano

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    André Marques Mansano

    2012-04-01

    Full Text Available PURPOSE: To evaluate the effect of N-acetylcysteine, as a renoprotective agent, when administered early after anesthesia induction, against ischemia/reperfusion injury in rats anesthetized with isoflurane. METHODS: Eighteen male Wistar rats weighing > 300g were anesthetized with isoflurane. The internal jugular vein and the left carotid artery were dissected and cannulated. The animals were randomly divided into GAcetyl, receiving intravenous N-acetylcysteine, 300mg/kg, and GIsot, isotonic saline. After 30 minutes, right nephrectomy was performed and the left renal artery was clamped during 45 minutes. The animals were sacrificed after 48 hours and blood samples were taken after anesthetic induction and upon sacrificing of the animals to evaluate blood creatinine. The kidneys were sent for histological analysis. RESULTS: The variation in serum creatinine was 2.33mg/dL ± 2.21 in GAcetyl and 4.38mg/dL ± 2.13 in GIsot (p=0.074. Two animals presented intense tubular necrosis in GAcetyl, compared to 5 in GIsot. Only GAcetyl presented animals free of tubular necrosis (two and tubular degeneration (one. CONCLUSION: After renal ischemia/reperfusion, the rats which were given N-acetylcysteine presented less variation in serum creatinine and milder kidney injuries than the control group.OBJETIVO: Avaliar o efeito da N-acetilcisteína na proteção renal contra lesão de isquemia/reperfusão, quando administrada logo após a indução anestésica, em ratos anestesiados com isoflurano. MÉTODOS: Dezoito ratos Wistar machos pesando mais que 300g foram anestesiados com isoflurano. A jugular interna direita e a carótida esquerda foram dissecadas e canuladas. Os animais foram distribuídos aleatoriamente em GAcetil, recebendo N-acetilcisteína por via intravenosa, 300mg/kg, e GIsot, solução salina. Foi realizada nefrectomia direita e clampeamento da artéria renal esquerda por 45 min. Os animais foram sacrificados após 48h, sendo colhidas amostras sangu

  13. Effects of melatonin on mitochondria after cerebral isehemic reperfusion

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    Wang Hongyu

    2000-01-01

    Melatonin has been regarded as a free radical scavenger and antioxidant. In both in vitro and in vivo experiments. Melatonin was found to protect cells, tissues and organs against oxidative damage induced by a variety of free radical generating agents and processes, e.g., ischemic reperfusion. The mechanisms underlying these interactions have not been defined. The goal of the present study was to observe the effects of melatonin on rnitochondria after cerebral ischemic reperfusion and the mechanisms of neuroprotection of melatonin by gerbil ischemic model. Male Mongolian gerbils were subjected to 10 min of forebrain ischemia by occlusion of both common carotid arteries under anesthesia. Melatonin(0.8 mg/kg) was administrated intraperitoneum 30 min befbre arteries occlusion. We measured the respiratory function of mitochondria, the activities of ATPase, the free mitochondrial calcium contents and the GSH level of mitochondria. The results show that oxidative phosphorylation function of mitochondria was damaged after cerebral ischemic reperfusion. And mitochondrial calcium was overloaded after cerebral ischemic reperfusion. And the level of GSH in mitochondria decreased after cerebral ischemic reperfision. It is concluded that melatonin have neuroprotection effects after cerebral ischemic repertusion and this effects probably related to the protection mitochondria.

  14. The feasibility of using CDFI to evaluate rabbit renal ischemia-reperfusion injury%彩色多普勒血流显像评价兔肾缺血再灌注损伤的可行性研究

    Institute of Scientific and Technical Information of China (English)

    陈晓梅; 李明星; 宣吉晴; 罗志建; 李昆萍; 叶帆; 张敏

    2012-01-01

    目的:探讨彩色多普勒血流显像(CKFI)评价肾缺血再灌注损伤发生的可行性.方法:48只大白兔随机分为假手术对照(S)组、缺血再灌注(I/R)组.应用CDFI检测各级兔肾动脉的血流动力学变化,测定兔肾组织肿瘤坏死因子α(TNF-α)的平均光密度(OD)并做相关性分析.结果:与S组比较,I/R 2 h组无明显血流动力学改变,I/R 8 h、24 h组分别出现SRA、IRA的RI增大和MRA、SRA、IRA的Vmax、PI、RI增大(P<0.05).I/R8h,24 h组TNF-α的OD高于S组(P<0.05).I/R各组MRA、SRA和IRA的Vmax,PI,RI与兔肾组织TNF-α的OD变化呈正相关(P<0.05).结论:CDFI是一种无创、及时的评价肾缺血再灌注损伤发生的可行方法.%Objective To study the feasibility of using CDFI to evaluate rabbit renal ischemia-reperfusion injury. Methods 48 rabbits were randomly divided into sham operation control group (S) and ischemia-reperfusion injury group ( I/R) .The hemodynamicparametersof rabbit renal artery and the expression of TNF-a in rabbit kidney tissue were respectively measured by color Doppler flow imaging (CDFI) and TNF-a kit. The correlationanalysis was studied between CDFI parameters andTNF-a expression. Results I/R 2 h group had no significant changes in hemodynamic parameters compared to S group. The hemodynamic parameters of I/R long time group were significantly changed such as RI of rabbits SRA and IRA.The TNF-a level of rabbits renalwas increased in I/R 8 h、 24 h group. Vmax,PI,RI of rabbits MRA, SRA and IRA had positive correlation with TNF-alevel (P < 0.05). Conclusion CDFI is a feasible method to evaluate the incidence of renal ischemia/reperfusion injury.

  15. A correlative study on the resistance index of rabbit renal artery after ischemia-reperfusion and the TNF-α expression in renal tissue%缺血再灌注的兔肾动脉阻力指数与肾组织TNF-α表达的相关性研究

    Institute of Scientific and Technical Information of China (English)

    陈晓梅; 李明星; 李昆萍; 宣吉晴

    2011-01-01

    目的 探讨肾组织肿瘤坏死因子(TNF-α)表达与肾缺血再灌注(I/R)后肾动脉阻力指数(RI)的相关性,为评价肾缺血再灌注损伤(IRI)的发生提供可行方法.方法 将48只大白兔随机分为假手术组、I/R组.应用彩色多普勒血流显像(CDFI)监测各组大白兔主肾动脉(MRA)、段动脉(SRA)、叶间动脉(IRA)的RI变化,免疫组化检测肾组织中TNF-α的表达.结果 与假手术组比较,I/R组大白兔再灌注2 h肾动脉无明显RI改变,再灌注8 h 及24 h分别出现SRA、IRA的 RI增大及MRA、SRA、IRA 的RI增大(P<0.05).I/R组8、24 h大白兔肾组织的TNF-α表达水平高于假手术组(P<0.05).各组MRA、SRA和IRA的RI与肾组织TNF-α表达呈正相关(P<0.05).结论 利用CDFI检测缺血再灌注的肾动脉的RI是一种无创、及时的评价肾IRI发生的可行方法.%Objective To explore the correlation of expression of tumor necrosis factor-alpha(TNF-α) in renal tissue and the resistance index (RI) of renal artery after renal ischemia-reperfusion(I/R) , and provide a feasible method to evaluate the occurrence of renal I/R injury. Methods 48 rabbits were randomly divided into sham operation group and I/R group. Color Doppler flow imaging (CDFI) was adopted to monitor the changes of RI of main renal artery (MRA) ,segmental renal artery (SRA) and interlobar renal artery (IRA) of rabbits in each group. Immunohistochemistry was employed to detect the expression of TNF-α in renal tissue. Results Compared with sham operation group, RI of renal artery showed no significant changes in rabbits subjected to 2 hours of reperfusion in I/R group,while that of SRA,IRA and that of MRA,SRA,IRA increased in rabbits subjected to 8 and 24 hours of reperfusion in I/R group,respectively(Prenal tissue of rabbits in I/R 8,24 h group was higher than that in sham operation group(P<0. 05). RI of MRA, SRA and IRA in each group had positive correlation with its TNF

  16. Toll-like receptor 4 regulates early endothelial activation during ischemic acute kidney injury

    Science.gov (United States)

    Chen, Jianlin; John, Reji; Richardson, James A.; Shelton, John M.; Zhou, Xin J.; Wang, Yanxia; Wu, Qing Qing; Hartono, John R.; Winterberg, Pamela D.; Lu, Christopher Y.

    2012-01-01

    Ischemic acute kidney injury (AKI) triggers an inflammatory response which exacerbates injury that requires increased expression of endothelial adhesion molecules. To study this further, we used in situ hybridization, immunohistology, and isolated endothelial cells, and found increased Toll-like receptor 4 (TLR4) expression on endothelial cells of the vasa rectae of the inner stripe of the outer medulla of the kidney 4 h after reperfusion. This increase was probably due to reactive oxygen species, known to be generated early during ischemic AKI, because the addition of hydrogen peroxide increased TLR4 expression in MS1 microvascular endothelial cells in vitro. Endothelial TLR4 may regulate adhesion molecule (CD54 and CD62E) expression as they were increased on endothelia of wild-type but not TLR4 knockout mice in vivo. Further, the addition of high-mobility group protein B1, a TLR4 ligand released by injured cells, increased adhesion molecule expression on endothelia isolated from wild-type but not TLR4 knockout mice. TLR4 was localized to proximal tubules in the cortex and outer medulla after 24 h of reperfusion. Thus, at least two different cell types express TLR4, each of which contributes to renal injury by temporally different mechanisms during ischemic AKI. PMID:20927041

  17. Impact of renal function on ischemic stroke and major bleeding rates in nonvalvular atrial fibrillation patients treated with warfarin or rivaroxaban: a retrospective cohort study using real-world evidence.

    Science.gov (United States)

    Weir, Matthew R; Berger, Jeffrey S; Ashton, Veronica; Laliberté, François; Brown, Kip; Lefebvre, Patrick; Schein, Jeffrey

    2017-10-01

    Renal dysfunction is associated with increased risk of cardiovascular disease and is an independent predictor of stroke and systemic embolism. Nonvalvular atrial fibrillation (NVAF) patients with renal dysfunction may face a particularly high risk of thromboembolism and bleeding. The current retrospective cohort study was designed to assess the impact of renal function on ischemic stroke and major bleeding rates in NVAF patients in the real-world setting (outside a clinical trial). Medical claims and Electronic Health Records were retrieved retrospectively from Optum's Integrated Claims-Clinical de-identified dataset from May 2011 to August 2014. Patients with NVAF treated with warfarin (2468) or rivaroxaban (1290) were selected. Each treatment cohort was stratified by baseline estimated creatinine clearance (eCrCl) levels. Confounding adjustments were made using inverse probability of treatment weights (IPTWs). Incidence rates and hazard ratios of ischemic stroke and major bleeding events were calculated for both cohorts. Overall, patients treated with rivaroxaban had an ischemic stroke incidence rate of 1.9 per 100 person-years (PY) while patients treated with warfarin had a rate of 4.2 per 100 PY (HR = 0.41 [0.21-0.80], p = .009). Rivaroxaban patients with an eCrCl below 50 mL/min (N = 229) had an ischemic stroke rate of 0.8 per 100 PY, while the rate for the warfarin cohort (N = 647) was 6.0 per 100 PY (HR = 0.09 [0.01-0.72], p = .02). For the other renal function levels (i.e. eCrCl 50-80 and ≥80 mL/min) HRs indicated no statistically significant differences in ischemic stroke risks. Bleeding events did not differ significantly between cohorts stratified by renal function. Ischemic stroke rates were significantly lower in the overall NVAF population for rivaroxaban vs. warfarin users, including patients with eCrCl below 50 mL/min. For all renal function groups, major bleeding risks were not statistically different between

  18. Remote ischemic preconditioning reduces perioperative cardiac and renal events in patients undergoing elective coronary intervention: a meta-analysis of 11 randomized trials.

    Directory of Open Access Journals (Sweden)

    Hanjun Pei

    Full Text Available BACKGROUND: Results from randomized controlled trials (RCT concerning cardiac and renal effect of remote ischemic preconditioning(RIPC in patients with stable coronary artery disease(CAD are inconsistent. The aim of this study was to explore whether RIPC reduce cardiac and renal events after elective percutaneous coronary intervention (PCI. METHODS AND RESULTS: RCTs with data on cardiac or renal effect of RIPC in PCI were searched from Pubmed, EMBase, and Cochrane library (up to July 2014. Meta-regression and subgroup analysis were performed to identify the potential sources of significant heterogeneity(I(2 ≥ 40%. Eleven RCTs enrolling a total of 1713 study subjects with stable CAD were selected. Compared with controls, RIPC significantly reduced perioperative incidence of myocardial infarction (MI [odds ratio(OR = 0.68; 95% CI, 0.51 to 0.91; P = 0.01; I(2 = 41.0%] and contrast-induced acute kidney injury(AKI (OR = 0.61; 95% CI, 0.38 to 0.98; P = 0.04; I(2 = 39.0%. Meta-regression and subgroup analyses confirmed that the major source of heterogeneity for the incidence of MI was male proportion (coefficient  = -0.049; P = 0.047; adjusted R(2 = 0.988; P = 0.02 for subgroup difference. CONCLUSIONS: The present meta-analysis of RCTs suggests that RIPC may offer cardiorenal protection by reducing the incidence of MI and AKI in patients undergoing elective PCI. Moreover, this effect on MI is more pronounced in male subjects. Future high-quality, large-scale clinical trials should focus on the long-term clinical effect of RIPC.

  19. Thyroid hormone preconditioning alleviates reperfusion-induced renal inflammation in mice%甲状腺激素T3减轻小鼠再灌注肾脏炎症反应

    Institute of Scientific and Technical Information of China (English)

    王盼梁; 何康; 张明; 张建军

    2012-01-01

    目的 观察甲状腺激素T3预处理对小鼠缺血-再灌注(IR)肾脏白介素-10(IL-10)、内源性白介素-1受体阻滞剂(IL-1Ra)表达的调控及其对中性粒细胞浸润的影响,探讨T3对IR肾脏的保护作用及可能的机制.方法 120只雄性C57BL/6小鼠随机分为4组(n=30):正常对照组(假手术)、单纯IR组(仅行肾脏IR)、T3+IR组(肾脏IR前48 h行T3预处理)、NaOH+IR组(肾脏IR前48 h注射等量0.1 mol/L NaOH),建立肾脏IR模型.各组于再灌注后24 h取血标本进行肾功能检测(肌酐、尿素氮);取肾脏标本采用PAS染色评估肾脏组织形态学改变,髓过氧化物酶(MPO)染色评估中性粒细胞浸润情况;real-time PCR检测肾脏再灌注后1、3、6、12、24、48 h的IL-10、IL-1Ra mRNA的表达.结果 再灌注后24 h T3+IR组血肌酐、尿素氮水平较单纯IR组降低(P<0.05)、肾脏损伤程度轻(P<0.05);MPO染色示T3+ IR组中性粒细胞浸润较单纯IR组明显减少(P<0.05).再灌注后12h,T3+IR组IL-10、IL-1Ra mRNA表达高于单纯IR组,并持续至再灌注后48 h,差异有统计学意义(P<0.05).单纯IR组和NaOH+IR组在上述各项指标的变化上无明显差异.结论 T3能在肾脏再灌注的晚期阶段发挥作用,促进IL-10、IL-1Ra的表达,减轻中性粒细胞浸润所产生的炎症反应,改善肾功能.%Objective To investigate the influence of thyroid hormone T3 preconditioning on interleukin-10 (IL-10) and interleukin-1 receptor antagonist (IL-1Ra) modulation and neutrophil infiltration after renal ishchemia/reperfusion (1R) in mice, so as to study the protective effect of T3 on IR kidney. Methods Totally 120 male C57BL/6 mice were randomly divided into four groups (n = 30), namely, control group (sham operation), IR group (only received renal IR), T3 + IR group (T3 preconditioning for 48 h before renal IR), and NaOH + IR group (received equivalent 0.1 mol/L NaOH soltuion 48 h before renal IR). The serum creatinine and blood urea nitrogen

  20. Endothelial pentraxin 3 contributes to murine ischemic acute kidney injury

    Science.gov (United States)

    Chen, Jianlin; Matzuk, Martin M.; Zhou, Xin J.; Lu, Christopher Y.

    2012-01-01

    Toll-like receptor 4 (TLR4), a receptor forDamage Associated Molecular Pattern Molecules and also the lipopolysaccharide receptor, is required for early endothelial activation leading to maximal inflammation and injury during murine ischemic acute kidney injury. DNA microarray analysis of ischemic kidneys from TLR4-sufficient and deficient mice showed that pentraxin 3 (PTX3) was upregulated only on the former while transgenic knockout of PTX3 ameliorated acute kidney injury. PTX3 was expressed predominantly on peritubular endothelia of the outer medulla of the kidney in control mice. Acute kidney injury increased PTX3 protein in the kidney and the plasma where it may be a biomarker of the injury. Stimulation by hydrogen peroxide, or the TLR4 ligands recombinant human High-Mobility Group protein B1 or lipopolysaccharide, induced PTX3 expression in the Mile Sven 1 endothelial cell line and in primary renal endothelial cells suggesting that endothelial PTX3 was induced by pathways involving TLR4 and reactive oxygen species. This increase was inhibited by conditional endothelial knockout of Myeloid differentiation primary response gene 88, a mediator of a TLR4 intracellular signaling pathway. Compared to wild type mice, PTX3 knockout mice had decreased endothelial expression of cell adhesion molecules at 4 hours of reperfusion possibly contributing to a decreased early maladaptive inflammation in the kidneys of knockout mice. At 24 hours of reperfusion, PTX3 knockout increased expression of endothelial adhesion molecules when regulatory and reparative leukocytes enter the kidney. Thus, endothelial PTX3 plays a pivotal role in the pathogenesis of ischemic acute kidney injury. PMID:22895517

  1. Acute renal failure is associated with higher death and disability in patients with acute ischemic stroke: analysis of nationwide inpatient sample.

    Science.gov (United States)

    Saeed, Fahad; Adil, Malik M; Khursheed, Faraz; Daimee, Usama A; Branch, Lionel A; Vidal, Gabriel A; Qureshi, Adnan I

    2014-05-01

    Acute renal failure (ARF) in setting of acute ischemic stroke (AIS) is associated with worse outcome. We sought to determine the prevalence of ARF and effect on outcomes of patients with AIS. Data from all patients admitted to US hospitals between 2002 and 2010 with a primary discharge diagnosis of ischemic stroke and secondary diagnosis of ARF were included. The effect of ARF on rates of intracerebral hemorrhage and discharge outcomes was analyzed after adjusting for potential confounders using logistic regression analysis. Of 7,068,334 patients with AIS, 372,223 (5.3%) had ARF during hospitalization. Dialysis was required in 2364 (0.6%) of 372,223 patients. Patients with AIS with ARF had higher rates of moderate to severe disability (41.3% versus 30%; P<0.0001), intracerebral hemorrhage (1.0% versus 0.5%; P<0.0001), and in-hospital mortality (8.4% versus 2.9%; P<0.0001) compared with those without ARF. After adjusting for confounding factors, patients with AIS with ARF had higher odds of moderate to severe disability (odds ratio, 1.3; 95% confidence interval, 1.3-1.4; P<0.0001), intracerebral hemorrhage (odds ratio, 1.4; 95% confidence interval, 1.3-1.6; P<0.0001), and death (odds ratio, 2.2; 95% confidence interval, 2.0-2.2; P<0.0001). ARF in patients with AIS is associated with significantly higher rates of moderate to severe disability at discharge and in-hospital mortality.

  2. Protective Effect of Alpha Lipoic Acid on Rat Sciatic Nerve Ischemia Reperfusion Damage

    Science.gov (United States)

    Turamanlar, Ozan; Özen, Oğuz Aslan; Songur, Ahmet; Yağmurca, Murat; Akçer, Sezer; Mollaoğlu, Hakan; Aktaş, Cevat

    2015-01-01

    Background: Alpha lipoic acid is a potent antioxidant that plays numerous roles in human health. This study examined the effect of ALA on rat sciatic nerve ischemia reperfusion damage. Aims: Protective effect of alpha lipoic acid (ALA) on sciatic nerve following ischemia-reperfusion in rats was investigated by using light microscopy and biochemical methods. Provided that the protective effect of ALA on sciatic nerve is proven, we think the damage to the sciatic nerve that has already occurred or might occur in patients for various reasons maybe prevented or stopped by giving ALA in convenient doses. Study Design: Animal experiment. Methods: Forty-two adult male Sprague-Dawley rats (250–300 grams) were used in this study. Rats were randomly divided into six groups including one control (Group 1), one sham (Group 2), two ischemia-reperfusion (Groups 3 and 4) and two treatment groups (Groups5 and 6). Doses of 60 and 100 mg/kg ALA were given (Group 5 and 6) intra peritoneally twice, 1 and 24 hours before the ischemia to each treatment group. Ischemia was carried out the abdominal aorta starting from the distal part of the renal vein for two hours followed by reperfusion for three hours. In immunohistochemical methods, fibronectin immunoreactivity was analyzed. For biochemical analyses, the tissues were taken in eppendorf microtubes and superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) enzyme activities as well as malondialdehyde (MDA) and nitricoxide (NO) levels were measured. Results: Fibronectin was observed to have increased significantly in the ischemia group; on the other hand, it was observed to have decreased in parallel to the doses in the ALA groups. Biochemical studies showed that SOD and GSHPx declined with ischemia-reperfusion, but the activities of these enzymes were increased in the treatment groups in parallel with the dose. It was found that increased MDA levels with ischemia-reperfusion were decreased in parallel with ALA dose. There were

  3. Protective effects of magnesium sulfate on renal ischemia-reperfusion injury in mice%硫酸镁对小鼠肾缺血再灌注损伤保护作用

    Institute of Scientific and Technical Information of China (English)

    李祖成; 李淑翠; 亢泽春; 王垣芳

    2012-01-01

    目的 观察硫酸镁对小鼠肾缺血再灌注损伤的抗氧化保护作用.方法 雄性小鼠随机分为假手术组、模型组和硫酸镁高、低剂量(120、60 mg/kg)组,无创动脉夹夹闭左肾蒂45 min和再灌注3h制备急性肾缺血再灌注损伤模型,检测肾脏指数、血清尿素氮(BUN)和肌酐含量、肾组织丙二醛(MDA)含量以及超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活力,HE染色观察肾组织学变化.结果 硫酸镁高、低剂量组小鼠肾指数分别为(0.72±0.05)和(0.74±0.07)、血清BUN含量为(12.36±2.24)和(15.58±1.92) mmol/L、血清肌酐水平为(98.23±4.37)和(114.63±6.24) μmol/L、肾组织MDA含量为(2.11±0.24)和(2.27±0.21) nmol/(mg·prot),肾组织SOD活力为(4.03±0.68)和(3.51±0.58) U/(mg·prot),硫酸镁高剂量组肾组织GSH-Px活力为(323.90±23.50)U/( mg· prot),与模型组比较,差异均有统计学意义(P<0.05),且肾组织病理变化较轻.结论 硫酸镁对小鼠急性肾缺血再灌注损伤具有保护作用,其机制可能与抑制脂质过氧化反应有关.%Objective To investigate whether magnesium sulfate could protect kidney against ischemia/reperfusion (I/R) injury. Methods Kunming male mice were randomly divided into sham group and model group and treated with magnesium sulfate (120 mg/kg and 60 mg/kg). I/R were induced by occlusion of left renal pedicle for 45 minutes followed by a three hours of reperfusion except sham group. After the reperfusion, the blood samples were collected and blood urea nitrogen(BUN) and serum creatinine were measured for the evaluation of renal function. The content of ma-londialdehyde( MDA),superoxide dismutase( SOD) activity,and glutathione peroxidase( GSH-Px) activity in left kidney tissues were detected,and histological examination was carried out. Results Compared with the model group,renal dysfunction of the mice treated with magnesium sulfate was improved; the content of MDA in the kidney tissues was

  4. 缺血前预处理对心脏缺血后再灌注损伤的影响及其机制%Effects of ischemic preconditioning with atorvastatin on heart ischemia-reperfusion injury and possible mechanism

    Institute of Scientific and Technical Information of China (English)

    任凌云; 刘志刚; 黄晓帆

    2014-01-01

    each).In control group,the rats were given cardiac perfusion continuous buffer.In IRI group,myocardia of rats accepted 30 min global ischemia and 120 min reperfusion.In Ator group,the rats were given 1 μmol/L Ator befor ischemia,and perfused for 30 min,followed by IRI.The myocardial ultrastructure,infarct size,hemodynamic,serum lactate dehydrogenase levels,adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD +) levels in three groups were observed.Results In IRI group and Ator group,arched upward ST segment elevation and T wave fusion after the anterior descending artery ligation were seen.The electrocardiogram (ECG) in the control group had no significant change after surgery.As compared with the IRI group,the myocardial infarction area in the Ator group was significantly decreased (P < 0.05).Microstructure showed that there was significant difference in the cardiomyocytes edema,myofibril,mitochondrial structure and glycogen granules among the three groups.After ischemia-reperfusion,the left ventricular systolic pressure (LVSP),peak velocity of left ventricular pressure drop (dp/dtmin) and heart rate (HR) values in the IRI group were decreased significantly,and the left ventricle end-diastolic pressure (LVEDP) values increased significantly (P < 0.05) as compared wiht the Ator group (P < 0.05).The lactate dehydrogenase (LDH) levels in the control group,IRI group and Ator group were (164.32 ± 20.84),(3589.63 ± 133.25) and (1703.25 ± 155.80) U/L respectively.The LDH levels in the IRI group were lower than in the control group,and those in IRI group were higher than in the Ator group (P < 0.05).The myocardial ATP and NAD + levels in the IRI group were decreased significantly as compared with the control group (P < 0.05),and increased as compared with the Ator group (P < 0.05).Conclusion Ischemic preconditioning with Ator for IRI can play an effective role in myocardial protection,which is achieved by activating the mitochondrial ATP

  5. Concomitant coronary and renal revascularization improves left ventricular hypertrophy more than coronary stenting alone in patients with ischemic heart and renal disease.

    Science.gov (United States)

    Dong, Hao-jian; Huang, Cheng; Luo, De-mou; Ye, Jing-guang; Yang, Jun-qing; Li, Guang; Luo, Jian-fang; Zhou, Ying-ling

    2016-01-01

    Percutaneous transluminal renal artery stenting (PTRAS) has been proved to have no more benefit than medication alone in treating atherosclerotic renal artery stenosis (ARAS). Whether PTRAS could improve left ventricular hypertrophy (LVH) and reduce adverse events when based on percutaneous coronary intervention (PCI) for patients with coronary artery disease (CAD) and ARAS is still unclear. A retrospective study was conducted, which explored the effect of concomitant PCI and PTRAS versus PCI alone for patients with CAD and ARAS complicated by heart failure with preserved ejection fraction (HFpEF). A total of 228 patients meeting inclusion criteria were divided into two groups: (1) the HFpEF-I group, with PCI and PTRAS; (2) the HFpEF-II group, with PCI alone. Both groups had a two-year follow-up. The left ventricular mass index (LVMI) and other clinical characteristics were compared between groups. During the follow-up period, a substantial decrease in systolic blood pressure (SBP) was observed in the HFpEF-I group, but not in the HFpEF-II group. There was marked decrease in LVMI in both groups, but the HFpEF-I group showed a greater decrease than the HFpEF-II group. Regression analysis demonstrated that PTRAS was significantly associated with LVMI reduction and fewer adverse events after adjusting for other factors. In HFpEF patients with both CAD and ARAS, concomitant PCI and PTRAS can improve LVH and decrease the incidence of adverse events more than PCI alone. This study highlights the beneficial effect of ARAS revascularization, as a new and more aggressive revascularization strategy for such high-risk patients.

  6. Role of TRPV1 channels in ischemia/reperfusion-induced acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Lan Chen

    Full Text Available OBJECTIVES: Transient receptor potential vanilloid 1 (TRPV1 -positive sensory nerves are widely distributed in the kidney, suggesting that TRPV1-mediated action may participate in the regulation of renal function under pathophysiological conditions. Stimulation of TRPV1 channels protects against ischemia/reperfusion (I/R-induced acute kidney injury (AKI. However, it is unknown whether inhibition of these channels is detrimental in AKI or not. We tested the role of TRPV1 channels in I/R-induced AKI by modulating these channels with capsaicin (TRPV1 agonist, capsazepine (TRPV1 antagonist and using Trpv1-/- mice. METHODS AND RESULTS: Anesthetized C57BL/6 mice were subjected to 25 min of renal ischemia and 24 hrs of reperfusion. Mice were pretreated with capsaicin (0.3 mg/kg body weight or capsazepine (50 mg/kg body weight. Capsaicin ameliorated the outcome of AKI, as measured by serum creatinine levels, tubular damage,neutrophil gelatinase-associated lipocalin (NGAL abundance and Ly-6B.2 positive polymorphonuclear inflammatory cells in injured kidneys. Neither capsazepine nor deficiency of TRPV1 did deteriorate renal function or histology after AKI. Measurements of endovanilloids in kidney tissue indicate that 20-hydroxyeicosatetraeonic acid (20-HETE or epoxyeicosatrienoic acids (EETs are unlikely involved in the beneficial effects of capsaicin on I/R-induced AKI. CONCLUSIONS: Activation of TRPV1 channels ameliorates I/R-induced AKI, but inhibition of these channels does not affect the outcome of AKI. Our results may have clinical implications for long-term safety of renal denervation to treat resistant hypertension in man, with respect to the function of primary sensory nerves in the response of the kidney to ischemic stimuli.

  7. Effect of olive oil on the cerebral reperfusion following ischemia injuries in rat

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    Javad Raouf Sarshoori

    2014-05-01

    Conclusion: The findings of the current study indicated that olive oil effectively reduced ischemia, helped to the reperfusion of injuries, and improved neurological outcome. Olive oil is also a potent neuroprotective factor that is able to prevent neurodegeneration of transient focal ischemia in the beginning of reperfusion at ischemic areas.

  8. Complement Depletion Protects Lupus-prone Mice from Ischemia-reperfusion-initiated Organ Injury

    Science.gov (United States)

    2012-10-25

    Complement depletion protects lupus-prone mice from ischemia-reperfusion- initiated organ injury Antonis Ioannou,1,3 Linda A. Lieberman,1 Jurandir J...Thiel S, Nielsen S, Taka- hashi K, Shi L, Ezekowitz A, Jensenius JC, Gadjeva M. Mannan- binding lectin recognizes structures on ischemic reperfused mouse

  9. 复灌Ⅰ号注射液对大鼠肢体缺血-再灌注损伤骨骼肌钙调蛋白表达的影响%Effect of Fuguan Injection Ⅰ on Calmodulin Expression in Skeletal Muscle of Ischemic-Reperfusion Injury Rats

    Institute of Scientific and Technical Information of China (English)

    朱付平; 冯先; 刘金龙; 姜仁建

    2012-01-01

    Objective: To study the influence of Fuguan Injection I on calmodulin expression in skeletal muscle of ischemic-reperfusion injury rats. Methods; Fifty-four rats were divided into 3 groups at random: control group, ischemic-reperfusion group (IR group) and Fuguan injection I intervention group ( I -IR group). The rats in control group did not undergo blockade of blood flow in posterior limbs. The ischemic reperfusion models of rats in rats' posterior limbs in IR group and I -IR group were established by the method suggested by Zhang Lianyuan. No drug was given before sacrifice in control group. One ml normal sodium was intraperitoneally injected 12 hours before ischemia* at ischemia and at reperfusion in the IR group. One ml Fuguan Injection I was intraperitoneally injected at the same time points as in IR group. Zero h, 2 h, 4 h? And 8 h after reperfusion, 100mg of gastrocnemius muscle was taken from the right posterior limb respectively in the three groups for RT-PCR test of RyRI and SERCA1. Results: (l)The skeletal muscle type RyR1 mRNA expression reached its highest level < lower than IR group) in I -IR group 2 hours after ischemia, indicating significant difference between I -IR group and IR group (P<0. 01). RyR1 mRNA expression decreased (lower than IR group) in I -IR group 8 hours after ischemia, also showing significant difference between I-IR group and IR group (P<0.05). (2)Within 8 hours after reperfusion, SERCA1 mRNA expression was gradually down-regulated both in I -IR group and IR group, with less decrease in I -IR group. Except for the 2-h time point, there were significant differences between IR group and 1 -IR group (P<0. 01). Conclusion:Fuguan Injection I can protect skeletal muscle during ischemic reperfusion injury. The reasons for this may be through the two-way regulation of RyRl mRNA expression to decrease calcium overload in the early time while to protect cell organ in the later time. And this may be the main molecular mechanism of

  10. Does Dexpantenol Protect the Kidney from Ischemia-Reperfusion Injury?

    Directory of Open Access Journals (Sweden)

    Sezen ÖZKISACIK

    2011-05-01

    Full Text Available OBJECTIVES: Tissue injury occurs following reperfusion after creation of ischemia. Plenty of chemical agents have been shown to protect from such an injury. We planned to evaluate the protective effect of dexpanthenol (dxp in ischemia-reperfusion injury. MATERIAL and METHODS: 24 adult rats were used and divided into 3 groups. A right nephrectomy was performed through a median laparotomy incision in all groups. Additionally, in group 1 (sham group, left nephrectomy was made 6 hours later without creation of ischemia. In group 2 (Saline group, the left kidney was left ischemic for 1 hour and reperfusion was established for 6 hours. Saline was administered intraperitoneally thirty minutes before creation of ischemia and just before reperfusion. In group 3 (Dexpanthenol group, the left kidney was left ischemic for 1 hour and reperfusion was established for 6 hours. Dxp (500 mg/kg was administered intraperitoneally thirty minutes before creation of ischemia and just before reperfusion. A left nephrectomy was performed at the end of the 6 hours of reperfusion. Nephrectomy specimens were histopathologically analysed for congestion, inflammation and necrosis. Tissue NO, glutathione reductase, catalase and MDA levels were measured. RESULTS: There was no significant differences between the groups histopathologically or biochemically. CONCLUSION: Dexpanthenol is the biologically active form of pantothenic acid and has an antioxidant effect. Our study was not in correlation with the literature regarding a protective effect of dxp on various organs via its antioxidant effect.

  11. Effect of Batroxobin on Neuronal Apoptosis During Focal Cerebral Ischemia and Reperfusion in Rats

    Institute of Scientific and Technical Information of China (English)

    吴卫平; 匡培根; 李振洲

    2001-01-01

    We have found that Batroxobin plays a protactive role in ischemic brain injury, which attracted us to investigate the effect of Batroxobin on apoptosis of neurons during cerebral ischemia and reperfusion. The apoptotic cells in ischemic rat brains at different reperfusion intervals were tested with method of TdT-mediated dUTP-DIG nick end labeling (TUNEL) and the effect of Batroxobin on the apoptosis of neurons was studied in left middle cerebral artery (LMCA) occlusion and reperfusion in rat models (n=18). The results showed that few scattered apoptosis cells were observed in right cerebral hemispheres after LMCA occlusion and reperfusion, and that a lot of apoptosis cells were found in left ischemic cortex and caudoputamen at 12h reperfusion, and they reached peak at 24h~48h reperfusion. However, in the rats pretreated with Batroxobin, the number of apoptosis cells in left cerebral cortex and caudoputamen reduced significantly and the neuronal damage was much milder at 24h reperfusion than that of saline-treated rats. The results indicate that administration of Batroxobin may reduce the apoptosis of neurons induced by cerebral ischemia and reperfusion and afford significant cerebroprotection in the model of focal cerebral ischemia and reperfusion.

  12. Protective effect of exogenous hydrogen sulfide on renal ischemia reperfusion injury in rats%外源性硫化氢在大鼠肾脏缺血再灌注损伤中的保护作用

    Institute of Scientific and Technical Information of China (English)

    覃志成; 闫燕; 李荣山

    2012-01-01

    目的 观察不同剂量外源性硫化氢(H2S)供体硫氢化钠对大鼠肾脏缺血再灌注损伤( IRI)的保护作用.方法 健康雄性Wistar大鼠28只随机分为4组,即假手术组( Sham)、肾缺血再灌注(IR)组、硫氢化钠(NaHS)高剂量组、硫氢化钠低剂量组.大鼠右肾切除后,以NaHS作为硫化氢的供体,NaHS高、低剂量组分别经左肾动脉插管,按照1.5 μmol/min、300 nmol/min的剂量连续15 min给药,假手术组及IR组给予同体积生理盐水.停药5 min 后,NaHS组和IR组用无损伤微动脉夹夹闭左侧肾蒂45 min后解除阻断,建立大鼠急性IRI模型,假手术组不夹闭左肾动脉,其他操作同模型组.于肾脏恢复血流24h时留取血和肾组织标本,检测血清尿素氮(BUN)、血肌酐(Scr);半定量分析肾脏病理损伤;检测肾组织H2S生成率;采用实时定量PCR法检测胱硫醚-β-合成酶(CBS)、胱硫醚-γ-裂解酶(CSE )mRNA表达.结果 与假手术组相比,IR组H2S生成率显著降低(P<0.01);CBS、CSE mRNA表达显著下降(P<0.01 );Scr、BUN显著升高(P<0.01);肾脏病理表现为急性肾小管坏死,且最严重.与IR组相比,NaHS预处理组H2S生成率升高(P<0.05);CBS、CSE mRNA表达升高(P<0.01 );Scr、BUN降低(P<0.01);病理损伤明显减轻.NaHS两个剂量组之间差异无统计学意义.结论 外源性H2S对大鼠IRI具有保护作用.%Objective To observe the protective effect of different doses sodium hydrosulfide (NaHS) as a donor of hydrogen sulfide on renal ischemia reperfusion injury (IRI).Methods Twenty-eight healthy male Wistar rats were randomly divided into 4 groups,namely sham operation (Sham) group (n =7),renal ischemia reperfusion (IR) group (n =7),sodium hydrosulfide (NaHS) high dose group (n=7),sodium hydrosulfide low dose group (n=7).After excision of the right kidney,two dose NaHS group (300 nmol/min,1.5 μmol/min) received 15-minute continuous administration via left renal artery.Sham group and IR

  13. 不同高压氧预处理对大鼠肾缺血再灌注损伤的研究%Effect of different programs of hyperbaric oygen preconditioning on renal ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    朱春艳; 刘宝; 周树生; 李矗; 沈建军

    2011-01-01

    Aim To investigate effects of different programs of preconditioning with hyperbaric oxygen( HBO ) on renal ischemia-reperfusion injury in rats. Methods Fifty SD rats were divided into five groups randomly : Group S : sham operation ( n = 10 ); Group I/R : rats l/R injury( n = 10 ); (;roup Hl-3 : rats were given HBO pretreatment 24 h before renal I/R for 4, 8 and 16 consecutive days respectively. In group I/R, rat model of renal ischemia-reperfusion injury ( IRI ) was established ( bilateral renal artery clamping, after 45 minutes. the clamps were removed ). During the 24-hour reperfusion period, the rat kidneys were observed for restoration of blood flow returning to their original color. In group S, Sham surgery consisted of the same surgical procedure except that clamps were not applied.Group H1-3 : rat was pretreated with HBO for 4. 8 and 16 days respectively, followed by the same surgical procedure. The animals were then killed and serum maleic dialdehyde( MDA ) . blood urea nitrogen( BUN ). serum creatinine( Scr ) were examined. Renal histology in I/R ARF was observed under an optical microscope. The expression of TNF-α and IL-6 were detected by ELISA. Results BUN, Cr,MDA, TNF-α . IL-6 in IR group were higher than those in S group ( P <0. 01 ). BUN, Cr, MDA. TNF-α. IL-6 in H1 , H2, H3 group were lower than those in the IR group ( P < 0. 05 ). TNF-α . IL-6 . MDA higher than the H2 group ( P < 0. 05 ). Preconditioning with 4 , 8 or 16 d of HBO attenuate the I/R ARF in kidney morphology and function. and decreased the TNF-α and IL-6 expression. Conclusion Preconditioning with hyperharic oxygen attenuates rat renal ischemia-reperfusion injury.%目的 研究不同时间高压氧预处理对大鼠肾脏缺血再灌注损伤的影响并探讨其机制.方法 雌性SD大鼠50只随机分为5组:假手术组(S组,n=10)打开腹腔不夹闭肾蒂;缺血再灌注组(IR组,n=10)夹闭双侧肾蒂30 min后再灌注;高压氧预处理1组(H1,n=10);

  14. Renoprotective effect of a combination of garlic and telmisartan against ischemia/reperfusion-induced kidney injury in obese rats.

    Science.gov (United States)

    Ali, Sousou Ibrahim; Alhusseini, Naglaa Fathy; Atteia, Hebatallah Husseini; Idris, Reham Abd El-Satar; Hasan, Rehab Abdallah

    2016-09-01

    Obesity enhances the frequency and severity of acute kidney injury (AKI). Telmisartan pre-treatment was used experimentally in the amelioration of ischemia/reperfusion (IR)-induced AKI. However, there is a lack of evidence regarding its beneficial effects on AKI in obese animals. The present study, therefore, aimed to explore the protective effects of garlic and/or telmisartan against renal damage induced by unilateral IR in obese rats. Meloxicam was used as a standard anti-inflammatory agent. Prophylactic oral administration of meloxicam (3 mg kg(-1)), garlic (500 mg kg(-1)) and/or telmisartan (5 and 10 mg kg(-1)) for 4 wk protected against renal function deterioration induced by IR in obese rats. Both doses of telmisartan significantly reduced serum total cholesterol and triacyglycerol levels as well as peri-renal adipocytes size and renal fibrosis. Renal nuclear factor-kappa B immunoreactivity, tumor necrosis factor-alpha content as well as interleukin-10, adiponectin receptor 1 and macrophages (M1, M2) polarization markers (CD11c, CD206) mRNA expressions were down-regulated in ischemic kidney tissues and white adipose tissues around them by all treatments. Moreover, garlic, telmisartan and their combinations significantly suppressed oxidative stress in renal ischemic tissues. Histological picture was also improved by these treatments. Interestingly, the combinations provided a greater protection than their monotherapy in a dose-dependent manner. We suppose that this combination may be a promising prophylactic regimen for managing AKI in case of obesity. Thus, future experimental and clinical large-scale studies are necessary.

  15. 青藤碱减轻小鼠肾脏缺血再灌注损伤%Protective effects of sinomenine on renal ischemia/reperfusion injury in mice

    Institute of Scientific and Technical Information of China (English)

    王博; 徐达; 王锡智; 王祥慧; 周佩军; 邵琨; 舒心雨; 罗斐埜

    2011-01-01

    目的 研究青藤碱对小鼠肾脏缺血再灌注(IR)损伤的作用及其机制.方法 C57BL/6小鼠静脉注射青藤碱200 mg/kg,对照组注射等体积生理盐水,通过检测血清丙氨酸转氨酶(ALT)和血清肌酐(SCr)分析青藤碱对小鼠的肝、肾毒性.将C57BL/6小鼠分为3组,每组6只.假手术(SO)组小鼠仅接受中线开腹、双侧肾蒂游离及关腹操作;青藤碱处理(SIN处理)组小鼠建立肾脏IR损伤模型,并于肾脏缺血前经尾静脉注射青藤碱200 mg/kg;生理盐水处理(Saline)组小鼠肾脏缺血前经尾静脉注射等体积生理盐水.再灌注后6 h检测各组血清尿素氮(BUN)和SCr水平,观察肾脏组织形态学变化,检测各组肾小管上皮细胞凋亡情况,检测各组肾脏组织内巨噬细胞浸润,检测各组肾脏组织内中性粒细胞的浸润,检测各组肾脏组织内肿瘤坏死因子α(TNF-α)、CXC趋化因子配体10(CXCL-10)、细胞间粘附分子1(ICAM-1)和白细胞介素17(IL-17)mRNA的表达,检测肾脏组织内核因子(NF)-κB亚单位p65磷酸化水平.结果 青藤碱对小鼠血清ALT和SCr影响的差异无统计学意义(P>0.05).再灌注后6 h,SIN处理组小鼠血清BUN和SCr水平明显低于Saline组(P<0.01,P<0.05).与Saline组相比较,SIN处理组小鼠肾小管上皮细胞损伤情况较轻(P<0.01),肾小管上皮细胞凋亡明显减轻(P<0.05),肾脏组织内巨噬细胞及中性粒细胞浸润明显减弱(P<0.05),TNF-α、CXCL-10、ICAM-1和IL-17 mRNA表达明显降低(P<0.05,P<0.01).结论 静脉应用青藤碱200mg/kg对小鼠无明显肝、肾毒性,可减轻肾脏IR损伤,其机制可能与抑制肾脏再灌注后炎症反应有关.%Objective To evaluate the protective effect of sinomenine (SIN) on renal ischemia/reperfusion (I/R) in mice. Methods In the experiment one, 12 C57BL/6 mice were randomly divided into 2 groups: SIN group (mice were injected with 200 mg/kg SIN by tail vein) and control group (mice were injected with

  16. Meta-analysis of effectiveness of edaravone for treatment against ischemic-reperfusion injury in patients undergoing cardic operation with cardiopulmonary by-pass%依达拉奉对体外循环心脏手术患者心肌缺血再灌注损伤治疗作用的meta分析

    Institute of Scientific and Technical Information of China (English)

    黄建敏; 杜书章; 张晓坚

    2011-01-01

    Aim: To assess the effectiveness of edaravone for treatment against ischemic-reperfusion injury (IRI) in patients undergoing cardie operation with cardiopulmonary by-pass. Methods: The related articles were searched, Pubmed, Highwire Press, EMBASE, WAN FANG DATA.CNKI and China Biological Medcine Database from Apr. 2001 to Jul. 2010.The Revman 5.0 software was used for the meta analysis. ReSUltS:A total of 6 RCT (n =202) were identified. The level of methodology was classified as B. Compared with the control group,in edravone group,there are significant difference in the spontaneous return rates of hearts after aorta declamping was higher (RR = 1.54,95% C/= 1.05 -2.25.P =0.03) ; and also in plasma concentration of MDA( at 2 h,6 h and 24 h after aorta declamping) ,serum concentation of SOD(24 h after surgery operation 95% CI = 0. 47 ~ 1. 18, SMD = 0. 82, P < 0. 001), CK-MB and cTnl ( at 6 h and 24 h after aorta declamping). Conclusion:Edaravone may have some protective effect for the treatment against ischemic-reperfusion injuryin patients undergoing cardiac operation with cardiopulmonary by-pass.%目的:运用meta分析法评价依达拉奉对体外循环心脏手术患者心肌缺血再灌注损伤(IRI)的疗效。方法:运用Cochrane系统评价的方法,检索Pubmed、Highwire Press、EMBASE、中国知网、万方科技文献数据库和中国生物医学文献数据库的文献及其

  17. 前列地尔对兔肾缺血再灌注时细胞凋亡的保护作用%Alprostadil effects of prostavasin on apoptosis by renal ischemia-reperfusion injury in rabbits

    Institute of Scientific and Technical Information of China (English)

    郭凌燕; 胡世雄

    2011-01-01

    Objective To study the alprostadil effects of alprostadil on apoptosis by renal ischemia-reperfusion injury (IR[) in rabbits. Methods The rabbit IRI models were made, and randourly divided into three groups: control group, IR[group and prostavasin intervention group. The creatinine (Ct) and blood urea nitrogen (BUN) were determined. Malondialdehyde ( MDA), superoxide dismutase (SOD),myeloperoxidase ( MPO), bcl-2, bax, Caspase-3 and apoptosis were assayed at 60 min after reperfusion.Results The Cr and BUN levels in plasma in IRI group and Prostavasin intervention group were increased obviously after reperfusion. The Cr levels at 60 min after repeffusion in alprostadil intervention group (231.32 + 17. 57 ) μmol/L were significantly lower than in IRI group ( 390. 61 ± 20. 42 ) μ mol/L, ( P <0. 05 ). The levels of bcl-2, bax, Caspase-3 in the renal tissue in IRI group were significantly higher than in control group ( P < 0. 05 ), and those in alprostadil intervention group were lower than in IRI group, but markedly higher than in control group (P < 0. 05 ). The number of apoptotic cells in alprostadil intervention group and IRI group was increased as compared with control group, and that in alprostadil intervention group was reduced as compared with IRI group. The contents of MDA, SOD and MPO in renal tissue of IRI group and Prostavasin intervention group were significantly higher than in control group ( P < 0. 05 ), and those in IRI group were significantly lower than in alprostadil intervention group (P <0. 05 ). Conclusion Alprostadil could be used to protect renal ischemia-reperfusion injury probably by decreasing oxygen free radicals generation, inhibiting neutrophils aggregating and activating in the renal tissues, thereby inhibiting the expression of bcl-2, bax, Caspase-3.%目的 观察前列地尔对兔肾缺血再灌注损伤时肾小管上皮细胞凋亡的保护作用.方法 建立兔肾缺血再灌注损伤动物模型,将实验兔随机分为3

  18. Mesenchymal Stromal Cell-Derived Factors Promote Tissue Repair in a Small-for-Size Ischemic Liver Model but Do Not Protect against Early Effects of Ischemia and Reperfusion Injury

    NARCIS (Netherlands)

    S.M.G. Fouraschen (Suomi M. G.); J.H. Wolf (Joshua H.); L.J.W. van der Laan (Luc); P.E. de Ruiter (Petra E.); W. Hancock; J.P. Van Kooten (Job P.); M.M.A. Verstegen (Monique); K.M. Olthoff (Kim); J. de Jonge (Jeroen)

    2015-01-01

    textabstractLoss of liver mass and ischemia/reperfusion injury (IRI) are major contributors to postresectional liver failure and small-for-size syndrome. Mesenchymal stromal cell-(MSC-) secreted factors are described to stimulate regeneration after partial hepatectomy. This study investigates if liv

  19. Crosstalk between Complement and Toll-like Receptor Activation in Relation to Donor Brain Death and Renal Ischemia-Reperfusion Injury

    NARCIS (Netherlands)

    Damman, Jeffrey; Daha, Mohamed R.; van Son, Willem J.; Leuvenink, Henri G.; Ploeg, Rutger J.; Seelen, Marc A.

    2011-01-01

    Two central pathways of innate immunity, complement and Toll-like receptors (TLRs), play an important role in the pathogenesis of renal injury inherent to kidney transplantation. Recent findings indicate close crosstalk between complement and TLR signaling pathways. It is suggested that mitogen acti

  20. Crosstalk between Complement and Toll-like Receptor Activation in Relation to Donor Brain Death and Renal Ischemia-Reperfusion Injury

    NARCIS (Netherlands)

    Damman, Jeffrey; Daha, Mohamed R.; van Son, Willem J.; Leuvenink, Henri G.; Ploeg, Rutger J.; Seelen, Marc A.

    2011-01-01

    Two central pathways of innate immunity, complement and Toll-like receptors (TLRs), play an important role in the pathogenesis of renal injury inherent to kidney transplantation. Recent findings indicate close crosstalk between complement and TLR signaling pathways. It is suggested that mitogen acti

  1. Simplifying electrocardiographic assessment in STEMI reperfusion management: Pros and cons.

    Science.gov (United States)

    Wong, Cheuk-Kit

    2017-01-15

    Current guidelines on STEMI reperfusion management do not incorporate further electrocardiographic details over the presence of significant ST elevation. Fibrinolysis is considered an alternative therapy to primary PCI if there is a long PCI-related delay, but the 2 therapies should not be combined. Meanwhile, reperfusion for ischemic stroke has evolved on mechanistic understanding - reperfusion benefit being greatest in the patient with small "core" infarct and large ischemic "penumbra". Fibrinolysis is not regarded as an alternative to mechanical thrombectomy, and the 2 therapies can be combined. In this article describing how reperfusion regimes have evolved along different paths for STEMI and for ischemic stroke, a new concept is made that in STEMI infarct lead Q waves can be the counterpart of the "core" and ST elevation the "penumbra". Suggestions to modify STEMI treatment algorithms are made, exploring further the relative role of (pre-hospital) fibrinolysis versus PCI particularly in younger patients presenting at the onset of their STEMI (no Q waves). In contrast, some patients particularly the older ones with more evolved STEMI (large Q waves present) may be much more suited for PCI despite expecting a long delay. The article finishes by describing potential future alterations in the method of reperfusion. Despite primary PCI being the well-established therapy, there are rooms for further research to optimize STEMI outcomes.

  2. 尤瑞克林对大鼠局灶性脑缺血再灌注损伤后APE/Ref-1表达的影响%Effect of Urinary kallikrein on the expression of apurinic apyrimidinic endonuclease/redox factor 1(APE/Ref-1) in cerebral tissue of rats subjected to cerebral ischemic-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    王言理; 陈晓兵; 许锁; 刘克喜; 石远峰

    2014-01-01

    ObjectiveTo investigate the effect of Urinary kallikrein on the expression of apurinic apyrimidinic endonuclease/redox factor 1 (APE/Ref-1) in rats which were subjected to reperfusion after middle cerebral artery occlusion (MCAO) for two hours. To explore the protective mechanism of Urinary kallikrein against ischemic/reperfusion brain injury.Methods 54 male Sprague-Dawley rats were randomly divided into three groups with 18 mice each group: control group (Con group), ischemic/reperfusion group (Model group), ischemic/reperfusion plus Urinary kallikrein group (URK group). Six rats from each group randomly selected were respectively subjected to the detection of APE/Ref-1 positive cell count in CA1 region of hippocampus by immunohistochernistry, the detection of cerebral infarct volume by TTC staining and the detection of the expression of protein APE/Ref-1 in hippocampus by Western blot.ResultsCompared with Con group, the levels of protein of expression of APE/Ref-1 in hippocampus significantly decreased (P<0.05), with the APE/Ref-1 positive cell count in CA3 region of hippocampus significantly lower (P<0.05), Urinary kallikreincan increase the protein of expression of APE/Ref-1 and the APE/Ref-1 positive cell count in CA1 region of hippocampus, but lower than that of Con group, Urinary kallikrein can decrease thecerebral infarct volume induced by the reperfusion after middle cerebral occlusion (MCAO).ConclusionUrinary kallikreincan increase the protein of expression of APE/Ref-1 after focal cerebral ischemia/reperfusion, that may be the other protective mechanism of Urinary kallikrein against ischemic/reperfusion brain injury.%目的:探讨尤瑞克林对大鼠局造性脑缺血再灌注损伤(I/R)后无嘌呤/无嘧啶核酸内切酶/氧化还原因子1(APE/Ref-1)表达的影响,进一步探讨尤瑞克林脑保护作用的机制。方法健康成年雄性SD大鼠54只,采用随机数字表法分为3组:空白对照组(Con组)(n=18),

  3. ApoSense: a novel technology for functional molecular imaging of cell death in models of acute renal tubular necrosis

    Energy Technology Data Exchange (ETDEWEB)

    Damianovich, Maya; Ziv, Ilan; Aloya, Tali; Grimberg, Hagit; Levin, Galit; Reshef, Ayelet; Bentolila, Alfonso; Cohen, Avi; Shirvan, Anat [NeuroSurvival Technologies (NST) Ltd., Petah Tikva (Israel); Heyman, Samuel N.; Shina, Ahuva [Mt.Scopus and the Hebrew University Medical School, Department of Medicine, Hadassah Hospital, Jerusalem (Israel); Rosen, Seymour [Beth Israel Deaconess Medical Center and Harvard Medical School, Department of Pathology, Boston, MA (United States); Kidron, Dvora [Meir Hospital, Department of Pathology, Kfar-Saba (Israel)

    2006-03-15

    Acute renal tubular necrosis (ATN), a common cause of acute renal failure, is a dynamic, rapidly evolving clinical condition associated with apoptotic and necrotic tubular cell death. Its early identification is critical, but current detection methods relying upon clinical assessment, such as kidney biopsy and functional assays, are insufficient. We have developed a family of small molecule compounds, ApoSense, that is capable, upon systemic administration, of selectively targeting and accumulating within apoptotic/necrotic cells and is suitable for attachment of different markers for clinical imaging. The purpose of this study was to test the applicability of these molecules as a diagnostic imaging agent for the detection of renal tubular cell injury following renal ischemia. Using both fluorescent and radiolabeled derivatives of one of the ApoSense compounds, didansyl cystine, we evaluated cell death in three experimental, clinically relevant animal models of ATN: renal ischemia/reperfusion, radiocontrast-induced distal tubular necrosis, and cecal ligature and perforation-induced sepsis. ApoSense showed high sensitivity and specificity in targeting injured renal tubular epithelial cells in vivo in all three models used. Uptake of ApoSense in the ischemic kidney was higher than in the non-ischemic one, and the specificity of ApoSense targeting was demonstrated by its localization to regions of apoptotic/necrotic cell death, detected morphologically and by TUNEL staining. (orig.)

  4. Effects of rapamycin on cerebral oxygen supply and consumption during reperfusion after cerebral ischemia.

    Science.gov (United States)

    Chi, O Z; Barsoum, S; Vega-Cotto, N M; Jacinto, E; Liu, X; Mellender, S J; Weiss, H R

    2016-03-01

    Activation of the mammalian target of rapamycin (mTOR) leads to cell growth and survival. We tested the hypothesis that inhibition of mTOR would increase infarct size and decrease microregional O2 supply/consumption balance after cerebral ischemia-reperfusion. This was tested in isoflurane-anesthetized rats with middle cerebral artery blockade for 1h and reperfusion for 2h with and without rapamycin (20mg/kg once daily for two days prior to ischemia). Regional cerebral blood flow was determined using a C(14)-iodoantipyrine autoradiographic technique. Regional small-vessel arterial and venous oxygen saturations were determined microspectrophotometrically. The control ischemic-reperfused cortex had a similar blood flow and O2 consumption to the contralateral cortex. However, microregional O2 supply/consumption balance was significantly reduced in the ischemic-reperfused cortex. Rapamycin significantly increased cerebral O2 consumption and further reduced O2 supply/consumption balance in the reperfused area. This was associated with an increased cortical infarct size (13.5±0.8% control vs. 21.5±0.9% rapamycin). We also found that ischemia-reperfusion increased AKT and S6K1 phosphorylation, while rapamycin decreased this phosphorylation in both the control and ischemic-reperfused cortex. This suggests that mTOR is important for not only cell survival, but also for the control of oxygen balance after cerebral ischemia-reperfusion.

  5. Ischemic Stroke

    Science.gov (United States)

    A stroke is a medical emergency. There are two types - ischemic and hemorrhagic. Ischemic stroke is the most common type. It is usually ... are at risk for having a more serious stroke. Symptoms of stroke are Sudden numbness or weakness ...

  6. Limb remote ischemic per-conditioning in combination with post-conditioning reduces brain damage and promotes neuroglobin expression in the rat brain after ischemic stroke

    Science.gov (United States)

    Ren, Changhong; Wang, Pengcheng; Wang, Brian; Li, Ning; Li, Weiguang; Zhang, Chenggang; Jin, Kunlin; Ji, Xunming

    2015-01-01

    Abstract Purpose: Limb remote ischemic per-conditioning or post-conditioning has been shown to be neuroprotective after cerebral ischemic stroke. However, the effect of combining remote per-conditioning with post-conditioning on ischemic/reperfusion injury as well as the underlying mechanisms are largely unexplored. Methods: Here, adult male Sprague Dawley rats were subjected to middle cerebral artery occlusion (MCAO). The limb ischemic stimulus was immediately applied after onset of focal ischemia (per-conditioning), followed by repeated short episodes of remote ischemia 24 hr after reperfusion (post-conditioning). The infarct volume, motor function, and the expression of neuroglobin (Ngb) were measured at different durations after reperfusion. Results: We found that a single episode of limb remote per-conditioning afforded short-term protection, but combining repeated remote post-conditioning during the 14 days after reperfusion significantly ameliorated cerebral ischemia/reperfusion injury. Interestingly, we also found that ischemic per- and post-conditioning significantly increased expression of Ngb, an oxygen-binding globin protein that has been demonstrated to be neuroprotective against stroke, at peri-infarct regions from day 1 to day 14 following ischemia/reperfusion. Conclusion: Our results suggest that the conventional per-conditioning combined with post-conditioning may be used as a novel neuroprotective strategy against ischemia-reperfusion injury, and Ngb seems to be one of the important players in limb remote ischemia-mediated neuroprotection. PMID:25868435

  7. Mangafodipir protects against hepatic ischemia-reperfusion injury in mice.

    Directory of Open Access Journals (Sweden)

    Romain Coriat

    Full Text Available INTRODUCTION AND AIM: Mangafodipir is a contrast agent used in magnetic resonance imaging that concentrates in the liver and displays pleiotropic antioxidant properties. Since reactive oxygen species are involved in ischemia-reperfusion damages, we hypothesized that the use of mangafodipir could prevent liver lesions in a mouse model of hepatic ischemia reperfusion injury. Mangafodipir (MnDPDP was compared to ischemic preconditioning and intermittent inflow occlusion for the prevention of hepatic ischemia-reperfusion injury in the mouse. METHODS: Mice were subjected to 70% hepatic ischemia (continuous ischemia for 90 min. Thirty minutes before the ischemic period, either mangafodipir (10 mg/kg or saline was injected intraperitoneally. Those experimental groups were compared with one group of mice preconditioned by 10 minutes' ischemia followed by 15 minutes' reperfusion, and one group with intermittent inflow occlusion. Hepatic ischemia-reperfusion injury was evaluated by measurement of serum levels of aspartate aminotransferase (ASAT activity, histologic analysis of the livers, and determination of hepatocyte apoptosis (cytochrome c release, caspase 3 activity. The effect of mangafodipir on the survival rate of mice was studied in a model of total hepatic ischemia. RESULTS: Mangafodipir prevented experimental hepatic ischemia-reperfusion injuries in the mouse as indicated by a reduction in serum ASAT activity (P<0.01, in liver tissue damages, in markers of apoptosis (P<0.01, and by higher rates of survival in treated than in untreated animals (P<0.001. The level of protection by mangafodipir was similar to that observed following intermittent inflow occlusion and higher than after ischemic preconditioning. CONCLUSIONS: Mangafodipir is a potential new preventive treatment for hepatic ischemia-reperfusion injury.

  8. 家兔全脑缺血再灌注期血清白细胞介素6水平与星状神经节阻滞的关系%Relationship between serum interleukin-6 level and stellate ganglion block in rabbit brain during ischemic-reperfusion period

    Institute of Scientific and Technical Information of China (English)

    全守波; 刘菊英; 王清秀; 杨光

    2005-01-01

    .05].星状神经节阻滞组与假手术组,生理盐水对照组与空白对照组组间差异无显著性(P>0.05);生理盐水对照组和空白对照组白细胞介素6水平在再灌注4~30 h时均高于假手术组,在再灌注10 h以后高于星状神经节阻滞组,差异均有显著性(P均<0.05).星状神经节阻滞组白细胞介素6升高的水平较生理盐水对照组、空白对照组显著降低(P<0.05).结论:星状神经节阻滞可明显降低家兔全脑缺血再灌注期间血清白细胞介素6的水平,提示星状神经节阻滞对全脑缺血再灌注损伤具有一定的保护和治疗作用,可作为治疗脑缺血再灌注损伤的一种新的途径.%BACKGROUND: Stellate ganglion block has many functions by improving brain circulation, modulating immunity, reducing plasmic catecholamine content, interleukin-6 is one of the most sensitive and important predictors and mediators for acute organic stress response, playing neuroprotective and neurotoxic double roles in brain ischemic injury.OBJECTIVE: To observe the effect of stellate ganglion block in rat brain during ischemic-reperfusion period on the changes of serum interleukin-6,in order to probe the role of stellate ganglion block in brain ischemicreperfusional injury.DESIGN: Randomized controlled experimentation.SETTING: Anaesthesia Department of Taihe Hospital Mfiliated to Yunyang Medical College, and Anaesthesia Department of Renmin Hospital Affiliated to Yunyang Medical College.MATERIALS: This experiment on animals was carried out at the Experimental Center of Taihe Hospital Affiliated to Yunyang Medical College at March 2003, interleukin-6 reagent kit and determination was provided and conducted by the immunity research institute of Chinese People's Liberation Army General Hospital. Totally 28 big-ear healthy rabbits in which male or female was not limited were selected and randomly divided into stellate ganglion group, saline comparison group, blank comparison group and sham

  9. Gadolinium decreases inflammation related to myocardial ischemia and reperfusion injury

    Directory of Open Access Journals (Sweden)

    Nicolosi Alfred C

    2009-12-01

    Full Text Available Abstract Background The lanthanide cation, gadolinium (GdCl3 protects the myocardium against infarction following ischemia and reperfusion. Neutrophils and macrophages are the main leukocytes responsible for infarct expansion after reperfusion. GdCl3 interferes with macrophage and neutrophil function in the liver by decreasing macrophage secretion of inflammatory cytokines and neutrophil infiltration. We hypothesized that GdCl3 protects against ischemia and reperfusion injury by decreasing inflammation. We determined the impact of GdCl3 treatment for reperfusion injury on 1 circulating monoctye and neutrophil counts, 2 secretion of inflammatory cytokines, and 3 influx of monocytes and neutrophils into the myocardium. Methods Rats (n = 3-6/gp were treated with saline or GdCl3 (20 μmol/kg 15 min prior to a 30 min period of regional ischemia and 120 min reperfusion. Sham rats were not subject to ischemia. Blood was collected either after 30 min ischemia or 120 min reperfusion and hearts were harvested at 120 min reperfusion for tissue analysis. Blood was analyzed for leukocytes counts and cytokines. Tissue was analyzed for cytokines and markers of neutrophil and monocyte infiltration by measuring myeloperoxidase (MPO and α-naphthyl acetate esterase (ANAE. Results GdCl3 did not affect the number of circulating neutrophils prior to ischemia. Two hours reperfusion resulted in a 2- and 3- fold increase in circulating monocytes and neutrophils, respectively. GdCl3 decreased the number of circulating monocytes and neutrophils during reperfusion to levels below those present prior to ischemia. Furthermore, after 120 min of reperfusion, GdCl3 decreased ANAE and MPO activity in the myocardium by 1.9-fold and 6.5-fold respectively. GdCl3 decreased MPO activity to levels below those measured in the Sham group. Serum levels of the major neutrophil chemoattractant cytokine, IL-8 were increased from pre-ischemic levels during ischemia and reperfusion in both

  10. Short fasting does not protect perfused ex vivo rat liver against ischemia-reperfusion. On the importance of a minimal cell energy charge.

    Science.gov (United States)

    Papegay, Bérengère; Stadler, Michaela; Nuyens, Vincent; Kruys, Véronique; Boogaerts, Jean G; Vamecq, Joseph

    2017-03-01

    Dietary restriction or reduced food intake was supported to protect against renal and hepatic ischemic injury. In this vein, short fasting was recently shown to protect in situ rat liver against ischemia-reperfusion. Here, perfused ex vivo instead of in situ livers were exposed to ischemia-reperfusion to study the impact of disconnecting liver from extrahepatic supply in energetic substrates on the protection given by short-term fasting. Perfused ex vivo livers using short (18 h) fasted compared with fed rats were submitted to ischemia-reperfusion and studied for release of cytolysis markers in the perfusate. Energetic stores are differently available in time and cell energetic charges (ratio of adenosine triphosphate plus half of the adenosine diphosphate concentrations to the sum of adenosine triphosphate + adenosine diphosphate + adenosine monophosphate concentrations), adenosine phosphates, and glycogen, which were further measured at different time points in livers. Short fasting versus feeding failed to protect perfused ex vivo rat livers against ischemia/reperfusion, increasing the release of cytolysis markers (potassium, cytochrome c, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase) in the perfusate during reoxygenation phase. Toxicity of short fasting versus feeding was associated with lower glycogen and energetic charges in livers and lower lactate levels in the perfusate. High energetic charge, intracellular content in glycogen, and glycolytic activity may protect liver against ischemia/reperfusion injury. This work does not question how much the protective role previously demonstrated in the literature for dietary restriction and short fasting. In fact, it suggests that exceeding the energy charge threshold value of 0.3 might trigger the effectiveness of this protective role. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. The cardioprotective effect of brief acidic reperfusion after ischemia in perfused rat hearts is not mimicked by inhibition of the Na+/H+ exchanger NHE1

    DEFF Research Database (Denmark)

    Andersen, Ann-Dorit; Bentzen, Bo Hjorth; Salling, H.

    2011-01-01

    Ischemic postconditioning (PostC), i.e. brief ischemia-reperfusion cycles before full reperfusion, is protective against cardiac ischemia/reperfusion (I/R) injury. Inhibition of the Na(+)/H(+) exchanger NHE1 and delayed intracellular pH-normalization have been proposed to underlie protection...

  12. Mild hypothermia reduces cardiac post-ischemic reactive hyperemia

    Directory of Open Access Journals (Sweden)

    Van der Pals Jesper

    2007-02-01

    Full Text Available Abstract Background In experimentally induced myocardial infarction, mild hypothermia (33–35°C is beneficial if applied prior to ischemia or reperfusion. Hypothermia, when applied after reperfusion seems to confer little or no benefit. The mechanism by which hypothermia exerts its cell-protective effect during cardiac ischemia remains unclear. It has been hypothesized that hypothermia reduces the reperfusion damage; the additional damage incurred upon the myocardium during reperfusion. Reperfusion results in a massive increase in blood flow, reactive hyperemia, which may contribute to reperfusion damage. We postulated that hypothermia could attenuate the post-ischemic reactive hyperemia. Methods Sixteen 25–30 kg pigs, in a closed chest model, were anesthetized and temperature was established in all pigs at 37°C using an intravascular cooling catheter. The 16 pigs were then randomized to hypothermia (34°C or control (37°C. The left main coronary artery was then catheterized with a PCI guiding catheter. A Doppler flow wire was placed in the mid part of the LAD and a PCI balloon was then positioned proximal to the Doppler wire but distal to the first diagonal branch. The LAD was then occluded for ten minutes in all pigs. Coronary blood flow was measured before, during and after ischemia/reperfusion. Results The peak flow seen during post-ischemic reactive hyperemia (during the first minutes of reperfusion was significantly reduced by 43 % (p Conclusion Mild hypothermia significantly reduces post-ischemic hyperemia in a closed chest pig model. The reduction of reactive hyperemia during reperfusion may have an impact on cardiac reperfusion injury.

  13. Affirmative effects of iloprost on apoptosis during ischemia-reperfusion injury in kidney as a distant organ.

    Science.gov (United States)

    Canacankatan, Necmiye; Sucu, Nehir; Aytacoglu, Barlas; Gul, Oguz E; Gorur, Aysegul; Korkmaz, Belma; Sahan-Firat, Seyhan; Antmen, Efsun S; Tamer, Lülüfer; Ayaz, Lokman; Vezir, Ozden; Kanik, Arzu; Tunctan, Bahar

    2012-01-01

    Apoptosis and its regulatory mechanisms take part in renal ischemia-reperfusion (I/R) injury which can result in acute renal failure and the inhibition of the caspase is considered as a new therapeutic strategy. In this context, we investigated the antiapoptotic and cytoprotective effects of iloprost, a prostacyclin analog, in kidney as a distant organ. Wistar albino rats were randomized into five groups (n = 12 in each) as sham, ischemia, I/R, iloprost (10 μg kg(-1)), and I/R + iloprost (10 μg kg(-1)). A 4 h reperfusion procedure was carried out after 4 h of ischemia. Caspase-8 was evaluated for death receptor-induced pathways, whereas caspase-9 was evaluated for mitochondria-dependent pathways and caspase-3 was investigated for overall apoptosis. Superoxide dismutase (SOD) enzyme activity and nitrite content as an indicator of nitric oxide (NO) production were also analyzed in kidney tissues. Caspases-3, -8, and -9 were all significantly elevated in both ischemia and I/R groups compared to the sham group; however, treatment with iloprost reduced caspases-3, -8, and -9. SOD enzyme activity was attenuated by iloprost when compared to ischemic rats. The different effects of NO were found which change according to the present situation in ischemia, I/R, and treatment with iloprost. These findings suggested that iloprost prevents apoptosis in both receptor-induced and mitochondria-dependent pathways in renal I/R injury and it may be considered as a cytoprotective agent for apoptosis. Understanding the efficiency of iloprost on the pathways for cell death may lead to an opportunity in the therapeutic approach for renal I/R injury.

  14. Myocardial ischemic conditioning: Physiological aspects and clinical applications in cardiac surgery.

    Science.gov (United States)

    Bousselmi, Radhouane; Lebbi, Mohamed Anis; Ferjani, Mustapha

    2014-04-01

    Ischemia-reperfusion is a major determinant of myocardial impairment in patients undergoing cardiac surgery. The main goal of research in cardioprotection is to develop effective techniques to avoid ischemia-reperfusion lesions. Myocardial ischemic conditioning is a powerful endogenous cardioprotective phenomenon. First described in animals in 1986, myocardial ischemic conditioning consists of applying increased tolerance of the myocardium to sustained ischemia by exposing it to brief episodes of ischemia-reperfusion. Several studies have sought to demonstrate its effective cardioprotective action in humans and to understand its underlying mechanisms. Myocardial ischemic conditioning has two forms: ischemic preconditioning (IPC) when the conditioning stimulus is applied before the index ischemia and ischemic postconditioning when the conditioning stimulus is applied after it. The cardioprotective action of ischemic conditioning was reproduced by applying the ischemia-reperfusion stimulus to organs remote from the heart. This non-invasive manner of applying ischemic conditioning has led to its application in clinical settings. Clinical trials for the different forms of ischemic conditioning were mainly developed in cardiac surgery. Many studies suggest that this phenomenon can represent an interesting adjuvant to classical cardioprotection during on-pump cardiac surgery. Ischemic conditioning was also tested in interventional cardiology with interesting results. Finally, advances made in the understanding of mechanisms that underlie the cardioprotective action of ischemic conditioning have paved the way to a new form of myocardial conditioning which is pharmacological conditioning.

  15. Reperfusion promotes mitochondrial dysfunction following focal cerebral ischemia in rats.

    Directory of Open Access Journals (Sweden)

    Jun Li

    Full Text Available BACKGROUND AND PURPOSE: Mitochondrial dysfunction has been implicated in the cell death observed after cerebral ischemia, and several mechanisms for this dysfunction have been proposed. Reperfusion after transient cerebral ischemia may cause continued and even more severe damage to the brain. Many lines of evidence have shown that mitochondria suffer severe damage in response to ischemic injury. The purpose of this study was to observe the features of mitochondrial dysfunction in isolated mitochondria during the reperfusion period following focal cerebral ischemia. METHODS: Male Wistar rats were subjected to focal cerebral ischemia. Mitochondria were isolated using Percoll density gradient centrifugation. The isolated mitochondria were fixed for electron microscopic examination; calcium-induced mitochondrial swelling was quantified using spectrophotometry. Cyclophilin D was detected by Western blotting. Fluorescent probes were used to selectively stain mitochondria to measure their membrane potential and to measure reactive oxidative species production using flow cytometric analysis. RESULTS: Signs of damage were observed in the mitochondrial morphology after exposure to reperfusion. The mitochondrial swelling induced by Ca(2+ increased gradually with the increasing calcium concentration, and this tendency was exacerbated as the reperfusion time was extended. Cyclophilin D protein expression peaked after 24 hours of reperfusion. The mitochondrial membrane potential was decreased significantly during the reperfusion period, with the greatest decrease observed after 24 hours of reperfusion. The surge in mitochondrial reactive oxidative species occurred after 2 hours of reperfusion and was maintained at a high level during the reperfusion period. CONCLUSIONS: Reperfusion following focal cerebral ischemia induced significant mitochondrial morphological damage and Ca(2+-induced mitochondrial swelling. The mechanism of this swelling may be mediated by

  16. Eficácia do pré-condicionamento isquêmico na proteção das lesões de isquemia e reperfusão hepáticas Ischemic preconditioning efficacy on ischemia-reperfusion injuries protection

    Directory of Open Access Journals (Sweden)

    Renato S. Lima

    2000-01-01

    Full Text Available O pré-condicionamento isquêmico foi estudado inicialmente no coração, onde atenua os efeitos lesivos da isquemia coronariana. Consiste na indução de breves períodos de isquemia seguidos de reperfusão, para tornar o órgão resistente a períodos mais longos de isquemia. Nesta investigação estudamos sua eficácia na proteção das lesões de isquemia-reperfusão hepáticas em ratos. Utilizaram-se 40 animais divididos em grupo Controle (C; grupo Shunt (S, submetido a exposição da cavidade abdominal por 95’; grupo Isquemia (I, submetido a exposição da cavidade abdominal por 10’, isquemia de 80’ e reperfusão de 5’; e grupo Pré-condicionamen