Ischemic preconditioning modulates ROS to confer protection in liver ischemia and reperfusion.
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ABSTRACT:
SUBMITTER: Bystrom P
PROVIDER: S-EPMC5491905 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:Ischemic preconditioning (IPC) and remote ischemic perconditioning (RIPer) confer protective effects against liver ischemia-reperfusion injury (IRI), but data about RIPer applying in liver transplantation is lacking. The study aimed to evaluate whether the combination of IPC and RIPer provides reinforced protective effects. C57BL/6 mice (160 pairs) were allocated into four groups: control, subjected to liver transplantation only; IPC, donor hilar was clamped for 10?min followed by 15?min of reperfusion; RIPer, three cycles of occlusion (5?min) and opening (5?min) of femoral vascular bundle were performed before reperfusion; IPC?+?RIPer, donors and recipients were subjected to IPC and RIPer respectively. Liver tissues were obtained for histological evaluation, TUNEL staining, malondialdehyde assays, GSH-Px assays, and NF-?B p65 protein and Bcl-2/Bax mRNA analyses. Blood samples were used to evaluate ALT, AST, TNF-?, NOx levels and flow cytometry. We found that protective efficacy of RIPer is less than IPC in terms of ALT, TNF-?, GSH-Px and NOx at 2?h postoperation, but almost equivalent at 24?h and 72?h postoperation. Except for Suzuki scores, ALT, Bcl-2/Bax mRNA ratio, other indices showed that combined treatment brought enhanced attenuation in IRI, compared with single treatment, through additive effects on antioxidation, anti-apoptosis, modulation of microcirculation disturbance, and inhibition of innate immune response. This study suggested a combined strategy that could enhance protection against IRI in clinical liver transplantation, otherwise, provided a hint that RIPer's mechanism might be partly or totally different from IPC in humoral pathway.
| S-EPMC6299280 | biostudies-literature
Project description:Diabetes mellitus (DM) exhibits a higher sensitivity to myocardial ischemia/reperfusion (I/R) injury and may compromise the effectiveness of cardioprotective interventions, including ischemic preconditioning. We previously found that liver ischemic preconditioning (RLIPC) could limit infarct size post I/R in non-diabetic rat hearts and further exerted anti-arrhythmic effects in diabetic or non-diabetic rats after myocardial I/R, however, little is known regarding the effect of RLIPC on infarct-sparing in diabetic hearts. In this study, we evaluated the protective effects of RLIPC on I/R injury in streptozotocin-induced type 1 diabetic rats. Type 1 diabetes mellitus was induced by one-time intraperitoneal injection of streptozotocin in Sprague-Dawley rats. Rats were exposed to 45 min of left anterior descend in (LAD) coronary artery occlusion, followed by 3 h of reperfusion. For liver ischemic preconditioning, four cycles of 5 min of liver I/R stimuli were performed before LAD occlusion. The cardioprotective effect of RLIPC was determined in diabetic rats. Compared to non-RLIPC treated DM rats, RLIPC treatment significantly reduced infarct size and cardiac tissue damage, inhibited apoptosis in diabetic hearts post I/R. RLIPC also improved cardiac functions including LVESP, LVEDP, dp/dtmax, and - dp/dtmax. In addition, RLIPC preserved cardiac morphology by reducing the pathological score post I/R in diabetic hearts. Finally, Westernblotting showed that RLIPC stimulated phosphorylation of ventricular GSK-3β and STAT-5, which are key components of RISK and SAFE signaling pathways. Our study showed that liver ischemic preconditioning retains strong cardioprotective properties in diabetic hearts against myocardial I/R injury via GSK-3β/STAT5 signaling pathway.
| S-EPMC7820418 | biostudies-literature
Project description:Although urgently needed in clinical practice, a cardioprotective therapeutic approach against myocardial ischemia/ reperfusion injury remains to be established. Remote ischemic preconditioning (rIPC) and ischemic preconditioning (IPC) represent promising tools comprising three entities: the generation of a protective signal, the transfer of the signal to the target organ, and the response to the transferred signal resulting in cardioprotection. However, in light of recent scientific advances, many controversies arise regarding the efficacy of the underlying signaling. We here show methods for the generation of the signaling cascade by rIPC as well as IPC in a mouse model for in vivo myocardial ischemia/ reperfusion injury using highly reproducible approaches. This is accomplished by taking advantage of easily applicable preconditioning strategies compatible with the clinical setting. We describe methods for using laser Doppler perfusion imaging to monitor the cessation and recovery of perfusion in real time. The effects of preconditioning on cardiac function can also be assessed using ultrasound or magnetic resonance imaging approaches. On a cellular level, we confirm how tissue injury can be monitored using histological assessment of infarct size in conjunction with immunohistochemistry to assess both aspects in a single specimen. Finally, we outline, how the rIPC-associated signaling can be transferred to the target cell via conservation of the signal in the humoral (blood) compartment. This compilation of experimental protocols including a conditioning regimen comparable to the clinical setting should proof useful to both beginners and experts in the field of myocardial infarction, supplying information for the detailed procedures as well as troubleshooting guides.
| S-EPMC5218813 | biostudies-literature
Project description:The lungs are highly susceptible to injury, including ischemia/reperfusion (I/R) injury. Pulmonary I/R injury can occur when correcting conditions such as primary pulmonary hypertension, and is also relatively common after lung transplantation or other cardiothoracic surgery. Methods to reduce pulmonary I/R injury are urgently needed to improve outcomes following procedures such as lung transplantation. Remote liver ischemic preconditioning (RLIPC) is an effective cardioprotective measure, reducing damage caused by subsequent cardiac I/R injury, but little is known about its potential role in pulmonary protection. Here, we analyzed the efficacy and mechanistic basis of RLIPC in a rat model of pulmonary I/R injury. RLIPC reduced lung I/R injury, lessening structural damage, inflammatory cytokine production and apoptosis. In addition, RLIPC preserved pulmonary function compared to controls following lung I/R injury. RLIPC stimulated phosphorylation of pulmonary STAT3, a component of the SAFE signaling pathway, but not phosphorylation of RISK pathway signaling proteins. Accordingly, STAT3 inhibition using AG490 eliminated the pulmonary protection afforded by RLIPC. Our data demonstrate for the first time that RLIPC protects against pulmonary I/R injury, via a signaling pathway requiring STAT3 phosphorylation.
| S-EPMC5955491 | biostudies-literature
Project description:Hepatic ischemia reperfusion (IR) injury contributes to the morbidity and mortality associated with liver surgery. This study investigated the protective function and mechanism of propylene glycol alginate sodium sulfate (PSS), a sulfated polysaccharide, in a mouse hepatic IR injury model. PSS (25 or 50 mg/kg) or saline were injected intraperitoneally to male Balb/c mice 1 h before 45 min of 70% warm hepatic ischemia and 2, 8, and 24 h of reperfusion. Serum and liver tissue samples were collected for evaluation of hepatocellular damage, liver histology, and assay of inflammatory cytokines, apoptosis- and autophagy-related proteins, and proteins in the mitogen-activated protein kinase (MAPKs). Histological injury and release of transaminases, and inflammatory cytokine production were significantly reduced by PSS pretreatment. The expression of apoptosis- and autophagy-related proteins, and the activation of MAPK signal, including jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and P38 were all affected by PSS treatment compared with IR model controls. PSS protected the liver from IR injury by suppressing the MAPK signaling and down-regulating inflammation, apoptosis, and autophagy.
| S-EPMC5680172 | biostudies-literature
Project description:Hepatic ischemia reperfusion injury (IRI) is an inevitable clinical problem for liver surgery. Polyethylene glycols (PEGs) are water soluble nontoxic polymers that have proven their effectiveness in various in vivo and in vitro models of tissue injury. The present study aims to investigate whether the intravenous administration of a high molecular weight PEG of 35?kDa (PEG 35) could be an effective strategy for rat liver preconditioning against IRI. PEG 35 was intravenously administered at 2 and 10?mg/kg to male Sprague Dawley rats. Then, rats were subjected to one hour of partial ischemia (70%) followed by two hours of reperfusion. The results demonstrated that PEG 35 injected intravenously at 10?mg/kg protected efficiently rat liver against the deleterious effects of IRI. This was evidenced by the significant decrease in transaminases levels and the better preservation of mitochondrial membrane polarization. Also, PEG 35 preserved hepatocyte morphology as reflected by an increased F-actin/G-actin ratio and confocal microscopy findings. In addition, PEG 35 protective mechanisms were correlated with the activation of the prosurvival kinase Akt and the cytoprotective factor AMPK and the inhibition of apoptosis. Thus, PEG may become a suitable agent to attempt pharmacological preconditioning against hepatic IRI.
| S-EPMC4770158 | biostudies-literature
Project description:The study for the first time systematically detect the dysregulated circRNAs and mRNAs in response to hepatic IRI and IPC intervention. Our profile and bioinformatic analysis provide numerous of novel clews on the understanding the pathophysiologic mechanism of IPC protection against hepatic IRI.
2021-02-28 | GSE164367 | GEO
Project description: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.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.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<0.05). The efficacy of ischemic preconditioning to reduce IR-injury, however, was lower in the patients and was even completely abolished during hyperglycemia.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.The study is registered at www.clinicaltrials.gov (NCT00184821).
| S-EPMC3504536 | biostudies-literature
Project description:Kidney ischemia-reperfusion (I/R) injury is a common cause of acute kidney injury. We tested whether dexmedetomidine (Dex), an alpha2 adrenoceptor (?2-AR) agonist, protects against kidney I/R injury. Sprague-Dawley rats were divided into four groups: (1) Sham-operated group; (2) I/R group (40 min ischemia followed by 24 h reperfusion); (3) I/R group + Dex (1 ?g/kg i.v. 60 min before the surgery), (4) I/R group + Dex (10 ?g/kg). The effects of Dex postconditiong (Dex 1 or 10 ?g/kg i.v. after reperfusion) as well as the effects of peripheral ?2-AR agonism with fadolmidine were also examined. Hemodynamic effects were monitored, renal function measured, and acute tubular damage along with monocyte/macrophage infiltration scored. Kidney protein kinase B, toll like receptor 4, light chain 3B, p38 mitogen-activated protein kinase (p38 MAPK), sirtuin 1, adenosine monophosphate kinase (AMPK), and endothelial nitric oxide synthase (eNOS) expressions were measured, and kidney transciptome profiles analyzed. Dex preconditioning, but not postconditioning, attenuated I/R injury-induced renal dysfunction, acute tubular necrosis and inflammatory response. Neither pre- nor postconditioning with fadolmidine protected kidneys. Dex decreased blood pressure more than fadolmidine, ameliorated I/R-induced impairment of autophagy and increased renal p38 and eNOS expressions. Dex downregulated 245 and upregulated 61 genes representing 17 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, in particular, integrin pathway and CD44. Ingenuity analysis revealed inhibition of Rac and nuclear factor (erythroid-derived 2)-like 2 pathways, whereas aryl hydrocarbon receptor (AHR) pathway was activated. Dex preconditioning ameliorates kidney I/R injury and inflammatory response, at least in part, through p38-CD44-pathway and possibly also through ischemic preconditioning.
| S-EPMC4186414 | biostudies-literature
Project description:To investigate the mechanism by which ischemic preconditioning (IPC) produces tissue tolerance to renal ischemia reperfusion injury in a pig model 15 female Yorkshire pigs were divided into three groups: 1: no IPC and 90 minutes warm ischemia; 2: remote IPC with an early window followed by 90 min warm ischemia; 3: remote IPC with a late window followed by warm ischemia 24 hrs later. Kidney tissues were obtained after 72 hours.
2016-09-02 | E-GEOD-72646 | biostudies-arrayexpress