Sevoflurane Prevents Liver Inflammatory Response Induced by Lung Ischemia-Reperfusion

Rancán, Lisa; Huerta, Luis; Cusati, Gabriel; Erquicia, I.; Isea, Jesús; Paredes, Sergio D.; Garcı́a, Cruz; Garutti, Ignacio; Simón, Carlos; Vara, Elena

doi:10.1097/tp.0000000000000408

Cited by 20 publications

(11 citation statements)

References 41 publications

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“…Pre-or postconditioning with volatile anesthetics is an effective protective strategy to decrease I/R injury to the liver. So far, its efficiency was tested in several models of hepatic I/R in humans 12,17 as well as in vivo, 18,19 showing decreased apoptosis and necrosis rate of hepatocytes. One possible mechanism involved in protection comprises involvement of hepatic energy metabolism.…”

Section: Discussionmentioning

confidence: 99%

Sevoflurane Protects Hepatocytes From Ischemic Injury by Reducing Reactive Oxygen Species Signaling of Hepatic Stellate Cells: Translational Findings Based on a Clinical Trial

Beck‐Schimmer

Z’graggen

Booy

et al. 2018

Anesthesia &Amp; Analgesia

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BACKGROUND Randomized controlled trials (RCTs) data demonstrate that sevoflurane postconditioning improves clinical outcomes of liver resection with inflow occlusion, presumably due to hepatocyte protection from ischemic injury. However, mechanisms remain unclear. This study examines liver biopsy samples obtained in an RCT of sevoflurane postconditioning to test the hypothesis that sevoflurane attenuates hepatocyte apoptosis. METHODS Messenger ribonucleic acid (mRNA) of pro-and antiapoptotic regulators Bax and B-cell lymphoma 2 (Bcl2) was examined in hepatic biopsies obtained during the RCT. Hepatic stellate cells (HSCs) and hepatocytes were exposed to hypoxia/reoxygenation (H/R) in vitro to evaluate the effect of sevoflurane postconditioning on apoptosis. The role of HSC as a potential apoptosis trigger in hepatocytes through the production of reactive oxygen species induced by H/R was explored by transferring supernatants from H/R-exposed HSC to hepatocytes as target cells. RESULTS In patients of the RCT, the Bax/Bcl2 mRNA ratio in liver tissue was markedly decreased in the sevoflurane arm (25% ± 21% reduction; P = .001). In vitro, H/R increased reactive oxygen species production in HSC by 33% ± 16% (P = .025), while it was abolished in the presence of sevoflurane (P < .001). In hepatocytes, caspase was minimally activated by H/R. However, incubation of hepatocytes with supernatants of HSC, previously exposed to H/R, increased caspase activity by 28% ± 13% (P < .001). When exposed to supernatants from HSC undergoing sevoflurane postconditioning, caspase activation in hepatocytes was reduced by 20% ± 9% (P < .001), similarly to the sevoflurane effect on the BAX/Bcl2 mRNA ratio in the liver samples. CONCLUSIONS The study shows that sevoflurane postconditioning affects apoptosis of hepatocytes after ischemia-reperfusion injury in patients. It also demonstrates that HSC may be the effector cells of sevoflurane protection.

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Section: Discussionmentioning

confidence: 99%

Sevoflurane Protects Hepatocytes From Ischemic Injury by Reducing Reactive Oxygen Species Signaling of Hepatic Stellate Cells: Translational Findings Based on a Clinical Trial

Beck‐Schimmer

Z’graggen

Booy

et al. 2018

Anesthesia &Amp; Analgesia

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“…Propofol has been reported to be associated with lower IL (interleukin)-6, IL-1β and TNF-α expression [30,31] and improves IL-10 secretion in traumatic inflammatory responses. Sevoflurane could also reverse the IR-induced decrease in IL-10 expression and inhibit IL-1β, IL-6 and TNF-α expression in cerebral focal ischemia-reperfusion damage in a rat model [32,33]. These changes in expression mediate cell death and can further enhance the pro-inflammatory response.…”

Section: Discussionmentioning

confidence: 94%

The Effects of Two Anesthetics, Propofol and Sevoflurane, on Liver Ischemia/Reperfusion Injury

Xu¹,

J²,

Wu³

et al. 2016

Cell Physiol Biochem

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Background: Propofol and sevoflurane are widely used in clinical anesthesia, and both have been reported to exert a protective effect in organ ischemia/reperfusion (IR). This study aims to investigate and compare the effects of propofol and sevoflurane on liver ischemia/reperfusion and the precise molecular mechanism. Methods and Materials: Rats were randomized into four groups: the sham group, I/R group, propofol treatment group (infused with 1% propofol at 500 µg· kg-1· min-1), and sevoflurane treatment group (infused with 3% (2 L/min) sevoflurane). The liver ischemia/reperfusion model was used to evaluate the hepatoprotective effect on ischemic injury. Liver enzyme leakage, liver cytokines and histopathological examination were used to evaluate the extent of hepatic ischemia/reperfusion injury. Oxidative stress was investigated by evaluating the levels of Malondialdehyde(MDA), Superoxide Dismutase(SOD) and NO. The terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling (TUNEL) assay and western blot were applied to detect apoptosis in the ischemic liver tissue and its mechanism. Results: Both propofol and sevoflurane attenuated the extent of hepatic ischemia/reperfusion injury which is evident from the hisopathological studies and alterations in liver enzymes such as AST and LDH by inhibiting Nuclear factor kappa B (NFκB) activation and subsequent alterations in inflammatory cytokines interleukin-1(IL-1), interleukin-6(IL-6), tumor necrosis factor-alpha (TNF-a) and increased IL10 release. Propofol exhibited a similar protective effect and a lower IL-1 release, while sevoflurane decreased TNF-a leakage more significantly. Meanwhile, oxidative stress was attenuated by reduced MDA and NO and elevated SOD release. The expression of antiapoptotic protein Bcl-2 and Bcl-xl were enhanced while that of apoptotic protein Bax and Bak were reduced by both propofol and sevoflurane to regulate hepatic apoptosis. In addition, propofol downregulated the phosphorylation of AKT and Bad protein, while sevoflurane downregulated the phosphorylation of p38. In addition, Both the treatments had no effect on the expression of AKT, Bad and p38. Conclusion: Both propofol and sevoflurane can protect the liver from ischemia/reperfusion injury by modulating the inflammatory responses reducing oxidative stress and liver apoptosis.

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“…Sevo urane (Sev) is a volatile anesthetic agent that offers hypnosis, analgesia and akinesia during surgical and procedural interventions [3]. The role of Sev during I/R injury has been underscored in the lung [4], brain [5] as well as heart [6].…”

Section: Introductionmentioning

confidence: 99%

Long non-coding NEAT1 weakens the protective role of sevoflurane on myocardial ischemia/reperfusion injury by mediating the microRNA-140/RhoA axis

Rui¹,

Wang²,

Xu³

2020

Preprint

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Background: The inhaled Sevoflurane (Sev) has been implicated to protect myocardial tissues against ischemia/reperfusion (I/R)-evoked injury. Nevertheless, the detailed mechanisms of Sev‐mediated cardioprotection remain basically unknown. This study intends to examine the roles of nuclear enriched abundant transcript 1 (NEAT1), a long non-coding RNA (lncRNA) during the cardioprotection exerted by Sev.Methods: We initially performed I/R surgery in mice, and Sev treatment was given during the perfusion, followed by the determination of cardiac function, myocardial infarction area and myocardial apoptosis for the validation of the model. Then, we conducted lncRNA microarray analysis on Sev-treated hearts to find out lncRNAs with significant differences in expression. The changes of myocardial I/R injury were evaluated by echocardiography, TTC staining and TUNEL assay after establishing mice with NEAT1 upregulation. Afterwards, the targeting miRNA of NEAT1 and the targeting mRNA of the miRNA were screened out through StarBase and microarray analyses to carry out rescue experiments.Results: NEAT1 was downregulated in Sev-treated cardiomyocytes. Overexpression of NEAT1 weakened cardiac function, increased infarct size and increased apoptosis in the presence of Sev. NEAT1 bound to microRNA (miR)-140, which was significantly upregulated in Sev-treated cardiomyocytes. Inhibition of miR-140 expression weakened the cardiac function of Sev-treated mice, increased infarct size and cardiomyocyte apoptosis. miR-140 mediated the RhoA pathway, and the RhoA activity inhibition attenuated miR-140 effects on Sev protection.Conclusion: Sev mitigates myocardial I/R injury by restoring NEAT1 expression and regulating the miR-140/RhoA axis.

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Sevoflurane Prevents Liver Inflammatory Response Induced by Lung Ischemia-Reperfusion

Abstract: The present results indicate that lung IR caused hepatic injury. Sevoflurane attenuated liver injury in a model of upper lobe left lung autotransplant in pigs.

Cited by 20 publications

References 41 publications

Sevoflurane Protects Hepatocytes From Ischemic Injury by Reducing Reactive Oxygen Species Signaling of Hepatic Stellate Cells: Translational Findings Based on a Clinical Trial

Sevoflurane Protects Hepatocytes From Ischemic Injury by Reducing Reactive Oxygen Species Signaling of Hepatic Stellate Cells: Translational Findings Based on a Clinical Trial

The Effects of Two Anesthetics, Propofol and Sevoflurane, on Liver Ischemia/Reperfusion Injury

Long non-coding NEAT1 weakens the protective role of sevoflurane on myocardial ischemia/reperfusion injury by mediating the microRNA-140/RhoA axis

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