scholarly journals Impact of S1P Mimetics on Mesenteric Ischemia/Reperfusion Injury

2020 ◽  
Vol 13 (10) ◽  
pp. 298
Author(s):  
Francesco Potì ◽  
Carmine Giorgio ◽  
Irene Zini ◽  
Jerzy-Roch Nofer ◽  
Valentina Vivo ◽  
...  
Keyword(s):  
Immune Cells ◽  
Mesenteric Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Action ◽  
Neutrophil Infiltration ◽  
Lipid Mediator ◽  
Receptor Subtypes ◽  
Barrier Integrity ◽  
Epithelial Barriers

Mesenteric ischemia/reperfusion (I/R), following the transient deprivation of blood flow to the gut, triggers an acute flogistic process involving the disruption of endothelial and epithelial barriers integrity, the activation of immune cells, and the abundant release of inflammatory mediators. Among them, the lipid mediator sphingosine-1-phosphate (S1P) is involved in maintaining epithelial and endothelial barrier integrity and in governing the migration of immune cells through the interaction with S1P1–5 receptors. Therefore, the present work aims to investigate the involvement of S1P signaling in intestinal I/R-induced injury by studying the effects of FTY720, the non-selective S1P1,3–5 agonist, and comparing them with the responses to ozanimod, selective S1P1,5 agonist, in a murine model of gut I/R. Intestinal edema, gut and lung neutrophil infiltration, and oxidative stress were evaluated through biochemical and morphological assays. The collected results highlight the protective action of FTY720 against the inflammatory cascade elicited by mesenteric I/R injury, mainly through the control of vascular barrier integrity. While these beneficial effects were mimicked by ozanimod and can be therefore attributed largely to the effects exerted by FTY720 on S1P1, the recruitment of myeloid cells to the injured areas, limited by FTY720 but not by ozanimod, rather suggests the involvement of other receptor subtypes.

Breathing nitric oxide plus hydrogen gas reduces ischemia-reperfusion injury and nitrotyrosine production in murine heart

2013 ◽  
Vol 305 (4) ◽  
pp. H542-H550 ◽  
Author(s):  
Toshihiro Shinbo ◽  
Kenichi Kokubo ◽  
Yuri Sato ◽  
Shintaro Hagiri ◽  
Ryuji Hataishi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiac Function ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Neutrophil Infiltration ◽  
Left Ventricular ◽  
Hydrogen Gas ◽  
Coronary Artery Ligation

Inhaled nitric oxide (NO) has been reported to decrease the infarct size in cardiac ischemia-reperfusion (I/R) injury. However, reactive nitrogen species (RNS) produced by NO cause myocardial dysfunction and injury. Because H2 is reported to eliminate peroxynitrite, it was expected to reduce the adverse effects of NO. In mice, left anterior descending coronary artery ligation for 60 min followed by reperfusion was performed with inhaled NO [80 parts per million (ppm)], H2 (2%), or NO + H2, starting 5 min before reperfusion for 35 min. After 24 h, left ventricular function, infarct size, and area at risk (AAR) were assessed. Oxidative stress associated with reactive oxygen species (ROS) was evaluated by staining for 8-hydroxy-2′-deoxyguanosine and 4-hydroxy-2-nonenal, that associated with RNS by staining for nitrotyrosine, and neutrophil infiltration by staining for granulocyte receptor-1. The infarct size/AAR decreased with breathing NO or H2 alone. NO inhalation plus H2 reduced the infarct size/AAR, with significant interaction between the two, reducing ROS and neutrophil infiltration, and improved the cardiac function to normal levels. Although nitrotyrosine staining was prominent after NO inhalation alone, it was eliminated after breathing a mixture of H2 with NO. Preconditioning with NO significantly reduced the infarct size/AAR, but not preconditioning with H2. In conclusion, breathing NO + H2 during I/R reduced the infarct size and maintained cardiac function, and reduced the generation of myocardial nitrotyrosine associated with NO inhalation. Administration of NO + H2 gases for inhalation may be useful for planned coronary interventions or for the treatment of I/R injury.

scholarly journals Effects of ovariectomy and estrogen on ischemia-reperfusion injury in hindlimbs of female rats

2001 ◽  
Vol 91 (4) ◽  
pp. 1828-1835 ◽  
Author(s):  
Nicole Stupka ◽  
Peter M. Tiidus
Keyword(s):  
Muscle Damage ◽  
Ischemia Reperfusion Injury ◽  
Serum Insulin ◽  
Ischemia Reperfusion ◽  
Neutrophil Infiltration ◽  
Female Rats ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
17Β Estradiol

The effects of estrogen and ovariectomy on indexes of muscle damage after 2 h of complete hindlimb ischemia and 2 h of reperfusion were investigated in female Sprague-Dawley rats. The rats were assigned to one of three experimental groups: ovariectomized with a 17β-estradiol pellet implant (OE), ovariectomized with a placebo pellet implant (OP), or control with intact ovaries (R). It was hypothesized that following ischemia-reperfusion (I/R), muscle damage indexes [serum creatine kinase (CK) activity, calpain-like activity, inflammatory cell infiltration, and markers of lipid peroxidation (thiobarbituric-reactive substances)] would be lower in the OE and R rats compared with the OP rats due to the protective effects of estrogen. Serum CK activity following I/R was greater ( P < 0.01) in the R rats vs. OP rats and similar in the OP and OE rats. Calpain-like activity was greatest in the R rats ( P < 0.01) and similar in the OP and OE rats. Neutrophil infiltration was assessed using the myeloperoxidase (MPO) assay and immunohistochemical staining for CD43-positive (CD43+) cells. MPO activity was lower ( P < 0.05) in the OE rats compared with any other group and similar in the OP and R rats. The number of CD43+ cells was greater ( P < 0.01) in the OP rats compared with the OE and R rats and similar in the OE and R rats. The OE rats had lower ( P < 0.05) thiobarbituric-reactive substance content following I/R compared with the R and OP rats. Indexes of muscle damage were consistently attenuated in the OE rats but not in the R rats. A 10-fold difference in serum estrogen content may mediate this. Surprisingly, serum CK activity and muscle calpain-like activity were lower ( P< 0.05) in the OP rats compared with the R rats. Increases in serum insulin-like growth factor-1 content ( P < 0.05) due to ovariectomy were hypothesized to account for this finding. Thus both ovariectomy and estrogen supplementation have differential effects on indexes of I/R muscle damage.

scholarly journals Proanthocyanidin protects intestine and remote organs against mesenteric ischemia/reperfusion injury

2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Ali Sizlan ◽  
Ahmet Guven ◽  
Bulent Uysal ◽  
Omer Yanarates ◽  
Abdulkadir Atim ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Mesenteric Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion

scholarly journals Role of curcumin in mesenteric ischemia – reperfusion injury in rats

2012 ◽  
Vol 113 (08) ◽  
pp. 465-470
Author(s):  
K. E. Nurullahoglu-Atalik ◽  
N. Okudan ◽  
M. Belviranli ◽  
H. Gokbel ◽  
M. Oz ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Mesenteric Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion

Proanthocyanidin Protects Intestine and Remote Organs Against Mesenteric Ischemia/Reperfusion Injury

2009 ◽  
Vol 33 (7) ◽  
pp. 1384-1391 ◽  
Author(s):  
Ali Sizlan ◽  
Ahmet Guven ◽  
Bulent Uysal ◽  
Omer Yanarates ◽  
Abdulkadir Atim ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Mesenteric Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion

Novel β-carboline-tripeptide conjugates attenuate mesenteric ischemia/reperfusion injury in the rat

2011 ◽  
Vol 46 (6) ◽  
pp. 2441-2452 ◽  
Author(s):  
Wei Bi ◽  
Yue Bi ◽  
Ping Xue ◽  
Yanrong Zhang ◽  
Xiang Gao ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Mesenteric Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion

scholarly journals Functional crosstalk between myeloid Foxo1–β-catenin axis and Hedgehog/Gli1 signaling in oxidative stress response

2020 ◽  
Author(s):  
Changyong Li ◽  
Mingwei Sheng ◽  
Yuanbang Lin ◽  
Dongwei Xu ◽  
Yizhu Tian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Cell Metabolism ◽  
Ischemia Reperfusion ◽  
Neutrophil Infiltration ◽  
Oxidative Stress Response ◽  
Proinflammatory Mediators ◽  
Hepatocellular Damage

AbstractFoxo1 transcription factor is an evolutionarily conserved regulator of cell metabolism, oxidative stress, inflammation, and apoptosis. Activation of Hedgehog/Gli signaling is known to regulate cell growth, differentiation, and immune function. However, the molecular mechanisms by which interactive cell signaling networks restrain oxidative stress response and necroptosis are still poorly understood. Here, we report that myeloid-specific Foxo1 knockout (Foxo1M-KO) mice were resistant to oxidative stress-induced hepatocellular damage with reduced macrophage/neutrophil infiltration, and proinflammatory mediators in liver ischemia/reperfusion injury (IRI). Foxo1M-KO enhanced β-catenin-mediated Gli1/Snail activity, and reduced receptor-interacting protein kinase 3 (RIPK3) and NIMA-related kinase 7 (NEK7)/NLRP3 expression in IR-stressed livers. Disruption of Gli1 in Foxo1M-KO livers deteriorated liver function, diminished Snail, and augmented RIPK3 and NEK7/NLRP3. Mechanistically, macrophage Foxo1 and β-catenin colocalized in the nucleus, whereby the Foxo1 competed with T-cell factor (TCF) for interaction with β-catenin under inflammatory conditions. Disruption of the Foxo1–β-catenin axis by Foxo1 deletion enhanced β-catenin/TCF binding, activated Gli1/Snail signaling, leading to inhibited RIPK3 and NEK7/NLRP3. Furthermore, macrophage Gli1 or Snail knockout activated RIPK3 and increased hepatocyte necroptosis, while macrophage RIPK3 ablation diminished NEK7/NLRP3-driven inflammatory response. Our findings underscore a novel molecular mechanism of the myeloid Foxo1–β-catenin axis in regulating Hedgehog/Gli1 function that is key in oxidative stress-induced liver inflammation and necroptosis.

scholarly journals Platelet-Associated CD40/CD154 Mediates Remote Tissue Damage after Mesenteric Ischemia/Reperfusion Injury

PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e32260 ◽  
Author(s):  
Peter H. Lapchak ◽  
Antonis Ioannou ◽  
Lakshmi Kannan ◽  
Poonam Rani ◽  
Jurandir J. Dalle Lucca ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Tissue Damage ◽  
Mesenteric Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion
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