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1.
Med Sci Monit ; 27: e932422, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34564688

RESUMO

BACKGROUND Perioperative neuro-cognitive disorders (PND) are preoperative and postoperative complications of multiple nervous systems, typically manifested as decreased memory and learning ability after surgery. It was used to replace the original definition of postoperative cognitive dysfunctions (POCD) from 2018. Our previous studies have shown that sevoflurane inhalation can lead to cognitive dysfunction in Sprague-Dawley rats, but the specific mechanism is still unclear. MATERIAL AND METHODS Thirty-six male Sprague-Dawley rats were randomly divided into 6 groups (n=6): the SD group was given 24-h acute sleep deprivation; Sevoflurane was inhaled for 2 h in the Sevo group. Two mL propofol was injected into the tail vein of rats in the Prop group. The rats in the SD+Sevo group and SD+Prop group were deprived of sleep before intervention in the same way as before. RESULTS We noted significant behavioral changes in rats treated with SIK3 inhibitors or tau phosphorylation agonists before propofol injection or sevoflurane inhalation, with associated protein levels and dendritic spine density documented. Sevoflurane anesthesia-induced cognitive impairment following acute sleep deprivation was more pronounced than sleep deprivation-induced cognitive impairment alone and resulted in increased brain SIK3 levels, increased phosphorylation of total tau and tau, and decreased acetylation modifications. After using propofol, the cognitive function returned to baseline levels with a series of reversals of cognitive dysfunction. CONCLUSIONS These results suggest that sevoflurane inhalation via the SIK3 pathway aggravates cognitive impairment after acute sleep deprivation and that propofol anesthesia reverses the effects of sleep deprivation by affecting modifications of tau protein.


Assuntos
Anestésicos Inalatórios/farmacologia , Anestésicos Intravenosos/farmacologia , Disfunção Cognitiva/fisiopatologia , Plasticidade Neuronal/efeitos dos fármacos , Propofol/farmacologia , Sevoflurano/farmacologia , Privação do Sono/fisiopatologia , Animais , Disfunção Cognitiva/etiologia , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Privação do Sono/complicações
2.
J Biol Regul Homeost Agents ; 35(3): 933-944, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34060267

RESUMO

The function of long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) has been revealed in injury caused by myocardial ischemia/reperfusion (I/R), however, its association with Sevoflurane (Sev), an anesthetic effective for regulating inflammation and oxidative stress, is not yet clear in I/R injury. The aim of this study was to functionally validate and elucidate the mechanism-of-action for Sev-mediated NEAT1 in myocardial I/R injury. Firstly, reduced NEAT1 was revealed in myocardial I/R injured mice treated with Sev. Moreover, restoration of NEAT1 could repress the alleviating role of Sev in cardiac function, infarct size and myocardial apoptosis in mice, while miR-140 was remarkably enhanced in myocardial tissues from mice treated with Sev. Furthermore, miR-140 was suggested and authenticated as a downstream biomolecule of NEAT1 with the help of a bioinformatics tool. Interestingly, miR-140 inhibitor played the same role as NEAT1 overexpression on the cardiac function, infarct size and apoptosis of mice. Finally, it was manifested that RhoA was a putative target of miR-140, which functioned importantly in the Sev/miR-140-mediated myocardial I/R injury. All in all, NEAT1 knockdown contributed to Sev-mediated myocardial I/R injury alleviation via the miR-140/RhoA axis.


Assuntos
MicroRNAs , Traumatismo por Reperfusão Miocárdica , RNA Longo não Codificante , Animais , Apoptose , Camundongos , MicroRNAs/genética , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos , RNA Longo não Codificante/genética , Sevoflurano/farmacologia , Proteína rhoA de Ligação ao GTP
3.
Biochem Biophys Res Commun ; 565: 21-28, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34090206

RESUMO

Preoperative anxiety is common and often comes with a higher probability of worse recovery. However, the neurological mechanism of the effect of preoperative anxiety on general anesthesia and subsequent awakening remains unknown. In this study, we report an anxious state results in delayed awakening in anxiety model mice from sevoflurane general anesthesia. More profound inhibition of DA neurons in the VTA contributes to delayed awakening. Optogenetic stimulation of VTA DA neurons can reverse the delay. The results indicate that VTA DA neurons may be involved in the delay in awakening from general anesthesia caused by anxiety.


Assuntos
Anestésicos Inalatórios/farmacologia , Ansiedade/tratamento farmacológico , Neurônios Dopaminérgicos/efeitos dos fármacos , Sevoflurano/farmacologia , Área Tegmentar Ventral/efeitos dos fármacos , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL
4.
Med Sci Monit ; 27: e930042, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34059615

RESUMO

BACKGROUND Perinatal hypoxia and subsequent reduction of cerebral blood flow leads to neonatal hypoxic-ischemic brain injury (HIBI), resulting in severe disability and even death. Preconditioning or post-conditioning with sevoflurane protects against cerebral injury. This study investigated the mechanism of sevoflurane in HIBI. MATERIAL AND METHODS The HIBI model of neonatal rats was established and the model rats were post-treated with sevoflurane. The oxygen-glucose deprivation (OGD) cell model was established, and the OGD cells were transfected with NRF2-siRNA plasmid and post-treated with sevoflurane. The Morris water maze test was used to detect the motor activity, spatial learning, and memory ability of HIBI rats. Histological stainings were performed to observe the area of cerebral infarction, record the number of neurons in the hippocampus, and assess neuron apoptosis. The levels of inflammatory factors were detected by ELISA. The protein levels of histone methyltransferase G9a and histone H3 lysine 9 (H3K9me2) were detected by western blot assay. The apoptosis was detected by flow cytometry. RESULTS Sevoflurane post-treatment significantly shortened the escape latency of HIBI neonatal rats, increased the density of neurons, reduced the area of cerebral infarction, and decreased the levels of inflammatory factors and neuronal apoptosis. Sevoflurane post-treatment decreased G9a and H3K9me2 levels, and G9a level was negatively correlated with NRF2 level. NRF2 silencing reversed the alleviation of sevoflurane post-treatment on OGD-induced cell injury. CONCLUSIONS Sevoflurane post-treatment promotes NRF2 expression by inhibiting G9a and H3K9me2, thus alleviating HIBI in neonatal rats.


Assuntos
Histona-Lisina N-Metiltransferase/metabolismo , Hipóxia-Isquemia Encefálica , Fator 2 Relacionado a NF-E2/metabolismo , Sevoflurano/farmacologia , Animais , Animais Recém-Nascidos , Comportamento Animal , Infarto Cerebral/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/prevenção & controle , Teste do Labirinto Aquático de Morris , Atividade Motora , Fármacos Neuroprotetores/farmacologia , Ratos , Resultado do Tratamento
5.
Aging (Albany NY) ; 13(9): 13333-13348, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33982674

RESUMO

This study aimed to explore effects of Sevoflurane on ischemia-reperfusion (I/R) injury after total knee arthroplasty (TKA). To explore potential molecular mechanism, Ras related dexamethasone induced 1 (RASD1), a Protein kinase A (PKA) activator, frequently associated with various models of I/R injury, was also investigated. In vivo mouse models with I/R injury after TKA and in vitro cell models with I/R injury were induced. Contents of creatinine kinase (CK), lactic dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA), serum levels of inflammatory factors, expression of PKA pathway-related genes and cell proliferation and apoptosis were measured. RASD1 was altered and PKA pathway was inhibited in mice and cells to elucidate the involvement of RASD1 and PKA pathway in Sevoflurane treatment on I/R injury. RASD1 was upregulated in I/R injury after TKA. Sevoflurane treatment or silencing RASD1 reduced RASD1 expression, CK, LDH and MDA contents, inflammation, apoptosis, but increased proliferation, SOD content, cAMP expression, and extents of PKA and cAMP responsive element binding protein (CREB) phosphorylation in skeletal muscle cells of I/R injury. Additionally, PKA pathway activation potentiated the therapeutic effect of Sevoflurane on I/R injury after TKA. Altogether, Sevoflurane treatment confines I/R injury after TKA via RASD1-mediated PKA pathway activation.


Assuntos
Proliferação de Células/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Sevoflurano/farmacologia , Proteínas ras/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Artroplastia do Joelho/métodos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Modelos Animais de Doenças , Camundongos , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/metabolismo
6.
J Pak Med Assoc ; 71(2(B)): 590-595, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33941941

RESUMO

Objectives: The Pain Rating index (PRi) is a new parameter for regulating analgesic depth of anaesthesia based on wavelet analysis. The aim of this study was to investigate the feasibility of PRi for depth regulation of sevoflurane anaesthesia. METHODS: We conducted a monocentric randomized controlled study from September 2017 to June 2018 in patients undergoing anterior cervical discectomy and fusion (ACDF) (n=44). Patients were randomly allocated into two groups and assigned 22 cases to each group: systolic blood pressure group (SBP group) and pain rating index group (PRi group). In SBP group, sevoflurane inhalation concentration (Cs) was adjusted to maintain SBP values at baseline values -20%~+20%; in PRi group, Cs was adjusted to maintain PRi values between 50 and 70. The primary endpoint was anaesthesia recovery time. Secondary endpoints included extubation time, sevoflurane consumption, number of intraoperative haemodynamic instability events /interventions, number of adverse events and postoperative visual analogue scale for pain. RESULTS: Patient demographic characteristics, surgical time and anaesthesia time did not differ between groups. Anaesthesia recovery time was shorter in PRi group than in SBP group (17.5±3.8min vs 21.5±2.8 min; P=0.001). Extubation time was also shorter in PRi group than in SBP group (21.9±1.7min vs 24.1±2.5min; P=0.001). Sevoflurane consumption was lower in PRi group than in SBP group (15.5±4.1ml vs 20.0±2.5ml; P=0.001). CONCLUSIONS: PRi was feasible to regulate depth of sevoflurane anaesthesia, which could shorten anaesthesia recovery time and extubation time, reduce sevoflurane consumption during general anaesthesia in patients undergoing cervical vertebra surgery.


Assuntos
Anestésicos Inalatórios , Éteres Metílicos , Período de Recuperação da Anestesia , Anestésicos Inalatórios/farmacologia , Pressão Sanguínea , Humanos , Éteres Metílicos/farmacologia , Dor , Sevoflurano/farmacologia
7.
Braz J Med Biol Res ; 54(7): e10213, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34008749

RESUMO

Sevoflurane (SEVO) is widely applied as an anesthetic, which exerts antitumor capacity in various cancers, including hepatocellular carcinoma (HCC). Previous studies indicated that long non-coding RNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) was upregulated, while microRNA-29a-3p (miR-29a-3p) was downregulated in HCC. Thus, we aimed to explore the roles of KCNQ1OT1 and miR-29a-3p in HCC cells exposed to SEVO. Cell proliferation, apoptosis, migration, and invasion were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and transwell assays, respectively. The levels of genes were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Furthermore, the interaction between miR-29a-3p and KCNQ1OT1 or chromebox protein homolog 3 (CBX3) was predicted by Starbase or Targetscan, and then confirmed by dual-luciferase reporter assay. We found that the levels of KCNQ1OT1 and CBX3 were decreased, while miR-29a-3p was increased in SEVO-treated HCC cells. KCNQ1OT1 overexpression weakened the inhibitory effects of SEVO on HCC cell proliferation, apoptosis, migration, and invasion. Interestingly, KCNQ1OT1 bound to miR-29a-3p, and miR-29a-3p targeted CBX3. KCNQ1OT1 upregulated CBX3 level by repressing miR-29a-3p expression. Furthermore, KCNQ1OT1 exerted tumor promotion in HCC cells via suppressing miR-29a-3p to regulate CBX3 expression. Collectively, our findings demonstrated that KCNQ1OT1 regulated the antitumor effects of SEVO on HCC cells through modulating the miR-29a-3p/CBX3 axis, providing a theoretical basis for the treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Canais de Potássio de Abertura Dependente da Tensão da Membrana , RNA Longo não Codificante , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Proteínas Cromossômicas não Histona , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Sevoflurano/farmacologia
8.
Oxid Med Cell Longev ; 2021: 6657529, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33986917

RESUMO

The cardioprotective effect of sevoflurane postconditioning (SPostC) is lost in diabetes that is associated with cardiac phosphatase and tensin homologue on chromosome 10 (PTEN) activation and phosphoinositide 3-kinase (PI3K)/Akt inactivation. T-LAK cell-originated protein kinase (TOPK), a mitogen-activated protein kinase- (MAPKK-) like serine/threonine kinase, has been shown to inactivate PTEN (phosphorylated status), which in turn activates the PI3K/Akt signaling (phosphorylated status). However, the functions of TOPK and molecular mechanism underlying SPostC cardioprotection in nondiabetes but not in diabetes remain unknown. We presumed that SPostC exerts cardioprotective effects by activating PTEN/PI3K/Akt through TOPK in nondiabetes and that impairment of TOPK/PTEN/Akt blocks diabetic heart sensitivity to SPostC. We found that in the nondiabetic C57BL/6 mice, SPostC significantly attenuated postischemic infarct size, oxidative stress, and myocardial apoptosis that was accompanied with enhanced p-TOPK, p-PTEN, and p-Akt. These beneficial effects of SPostC were abolished by either TOPK kinase inhibitor HI-TOPK-032 or PI3K/Akt inhibitor LY294002. Similarly, SPostC remarkably attenuated hypoxia/reoxygenation-induced cardiomyocyte damage and oxidative stress accompanied with increased p-TOPK, p-PTEN, and p-Akt in H9c2 cells exposed to normal glucose, which were canceled by either TOPK inhibition or Akt inhibition. However, either in streptozotocin-induced diabetic mice or in H9c2 cells exposed to high glucose, the cardioprotective effect of SPostC was canceled, accompanied by increased oxidative stress, decreased TOPK phosphorylation, and impaired PTEN/PI3K/Akt signaling. In addition, TOPK overexpression restored posthypoxic p-PTEN and p-Akt and decreased cell death and oxidative stress in H9c2 cells exposed to high glucose, which was blocked by PI3K/Akt inhibition. In summary, SPostC prevented myocardial ischemia/reperfusion injury possibly through TOPK-mediated PTEN/PI3K/Akt activation and impaired activation of this signaling pathway may be responsible for the loss of SPostC cardioprotection by SPostC in diabetes.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hiperglicemia/enzimologia , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sevoflurano/farmacologia , Animais , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/enzimologia , Coração/efeitos dos fármacos , Humanos , Hiperglicemia/sangue , Hiperglicemia/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Inibidores da Agregação Plaquetária/farmacologia , Distribuição Aleatória , Ratos , Transdução de Sinais/efeitos dos fármacos
9.
Pain Res Manag ; 2021: 5517150, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936350

RESUMO

Background: Pain aggravates the autonomic response to stress and raises neuroendocrine stress hormone levels. We compared the effects of propofol and sevoflurane on postoperative pain and neuroendocrine stress hormones. A prospective, randomized, and controlled trial was conducted with 60 patients. Methods: We randomly allocated patients to groups P (remifentanil/propofol, n = 30) and S (remifentanil/sevoflurane, n = 30). Preoperative blood samples were taken to measure serum adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), glucagon, cortisol, aldosterone, and prostaglandin E2 (PGE2) levels. Intraoperatively and postoperatively, clinical parameters were monitored at different time points. The hormone levels were again measured in the follicular fluid and blood postoperatively. Result: Demographic data were similar. The preoperative serum aldosterone levels were significantly higher in group P (p=0.001). Preoperative and postoperative serum ACTH, glucagon, cortisol, and PGE2 levels were significantly different in group P (p=0.009, p=0.004, p=0.029, and p=0.002); serum ACTH, glucagon, and PGE2 levels increased while serum cortisol levels decreased postoperatively. In group S, serum CRH and aldosterone levels, both increased in the postoperative period compared to the preoperative (p=0.001, p=0.006). Postoperatively, glucagon and PGE2 levels were both higher in group P than group S (p=0.019, p=0.015). In postoperative follicular fluid, glucagon and PGE2 levels were higher in group P, while cortisol levels were higher in group S (p=0.001, p=0.007, and p=0.001). Conclusion: The effects of anesthetic agents were different. In group P, in the preoperative and postoperative evaluation, ACTH, glucagon, and PGE2 increased postoperatively, while cortisol decreased. In group S, aldosterone and CRH increased postoperatively. Glucagon and PG E2 were higher in group P than S, postoperatively.


Assuntos
Anestésicos Inalatórios/uso terapêutico , Sistemas Neurossecretores/fisiopatologia , Recuperação de Oócitos/métodos , Dor Pós-Operatória/tratamento farmacológico , Propofol/uso terapêutico , Sevoflurano/uso terapêutico , Adolescente , Adulto , Anestésicos Inalatórios/farmacologia , Feminino , Humanos , Masculino , Propofol/farmacologia , Estudos Prospectivos , Sevoflurano/farmacologia , Adulto Jovem
10.
Commun Biol ; 4(1): 560, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980987

RESUMO

Accumulation and spread of tau in Alzheimer's disease and other tauopathies occur in a prion-like manner. However, the mechanisms and downstream consequences of tau trafficking remain largely unknown. We hypothesized that tau traffics from neurons to microglia via extracellular vesicles (EVs), leading to IL-6 generation and cognitive impairment. We assessed mice and neurons treated with anesthetics sevoflurane and desflurane, and applied nanobeam-sensor technology, an ultrasensitive method, to measure tau/p-tau amounts. Sevoflurane, but not desflurane, increased tau or p-tau amounts in blood, neuron culture medium, or EVs. Sevoflurane increased p-tau amounts in brain interstitial fluid. Microglia from tau knockout mice took up tau and p-tau when treated with sevoflurane-conditioned neuron culture medium, leading to IL-6 generation. Tau phosphorylation inhibitor lithium and EVs generation inhibitor GW4869 attenuated tau trafficking. GW4869 mitigated sevoflurane-induced cognitive impairment in mice. Thus, tau trafficking could occur from neurons to microglia to generate IL-6, leading to cognitive impairment.


Assuntos
Transporte Proteico/efeitos dos fármacos , Sevoflurano/farmacologia , Proteínas tau/metabolismo , Doença de Alzheimer/metabolismo , Anestésicos Inalatórios/farmacologia , Animais , Encéfalo/metabolismo , Disfunção Cognitiva/induzido quimicamente , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/fisiologia , Feminino , Hipocampo/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fosforilação , Transporte Proteico/fisiologia , Sevoflurano/metabolismo , Tauopatias/metabolismo , Tauopatias/fisiopatologia , Proteínas tau/fisiologia
11.
BMC Vet Res ; 17(1): 201, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34049559

RESUMO

BACKGROUND: The bispectral index (BIS) is an anaesthesia monitoring technique able to assess the level of central nervous system depression in humans and various animal species. In birds, it has been validated in chickens undergoing isoflurane anaesthesia. The aim of this study was to evaluate in an avian species the influence of isoflurane and sevoflurane on BIS, each at different minimum anaesthetic concentrations (MAC) multiples, alone or combined with butorphanol or medetomidine. Ten chickens (5 males and 5 females) underwent general anaesthesia with isoflurane or sevoflurane alone, and combined with either intramuscular administration of butorphanol (1 mg/kg) or medetomidine (0.1 mg/kg), in a prospective and cross-over study (i.e., 6 treatments per animal). BIS measurements were compared to heart rate (HR), non-invasive blood pressure (NIBP) and to a visual analogue scale (VAS) of anaesthesia depth. RESULTS: HR was significantly increased, and both NIBP and VAS were significantly reduced, with higher gas concentrations. NIBP (but not HR or VAS) was additionally affected by the type of gas, being lower at higher concentrations of sevoflurane. Butorphanol had no additional effect, but medetomidine led to differences in HR, NIBP, and in particular a reduction in VAS. With respect to deeper level of hypnosis at higher concentrations and the absence of difference between gases, BIS measurements correlated with all other measures (except with HR, where no significant relationship was found) The difference in BIS before (BISpre) and after stimulation (BISpost) did not remain constant, but increased with increasing MAC multiples, indicating that the BISpost is not suppressed proportionately to the suppression of the BISpre values due to gas concentration. Furthermore, neither butorphanol nor medetomidine affected the BIS. CONCLUSIONS: The difference of degree of central nervous system depression monitored by BIS compared with neuromuscular reflexes monitored by VAS, indicate that BIS records a level of anaesthetic depth different from the one deducted from VAS monitoring alone. BIS provided complementary information such as that medetomidine suppressed spinal reflexes without deepening the hypnotic state. As a consequence, it is concluded that BIS improves the assessment of the level of hypnosis in chickens, improving anaesthesia monitoring and anaesthesia quality in this species.


Assuntos
Butorfanol/farmacologia , Galinhas , Monitores de Consciência/veterinária , Isoflurano/farmacologia , Medetomidina/farmacologia , Sevoflurano/farmacologia , Anestésicos Combinados/farmacologia , Animais , Estudos Cross-Over , Feminino , Frequência Cardíaca/efeitos dos fármacos , Masculino , Estudos Prospectivos
12.
Anesthesiology ; 135(1): 136-150, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33914856

RESUMO

BACKGROUND: Sepsis is one of the leading causes of mortality in intensive care units, and sedation in the intensive care unit during sepsis is usually performed intravenously. The inhalative anesthetic sevoflurane has been shown to elicit protective effects in various inflammatory studies, but its role in peritonitis-induced sepsis remains elusive. The hypothesis was that sevoflurane controls the neutrophil infiltration by stabilization of hypoxia-inducible factor 1α and elevated adenosine A2B receptor expression. METHODS: In mouse models of zymosan- and fecal-induced peritonitis, male mice were anesthetized with sevoflurane (2 volume percent, 30 min) after the onset of inflammation. Control animals received the solvent saline. The neutrophil counts and adhesion molecules on neutrophils in the peritoneal lavage of wild-type, adenosine A2B receptor -/-, and chimeric animals were determined by flow cytometry 4 h after stimulation. Cytokines and protein release were determined in the lavage. Further, the adenosine A2B receptor and its transcription factor hypoxia-inducible factor 1α were evaluated by real-time polymerase chain reaction and Western blot analysis 4 h after stimulation. RESULTS: Sevoflurane reduced the neutrophil counts in the peritoneal lavage (mean ± SD, 25 ± 17 × 105vs. 12 ± 7 × 105 neutrophils; P = 0.004; n = 19/17) by lower expression of various adhesion molecules on neutrophils of wild-type animals but not of adenosine A2B receptor -/- animals. The cytokines concentration (means ± SD, tumor necrosis factor α [pg/ml], 523 ± 227 vs. 281 ± 101; P = 0.002; n = 9/9) and protein extravasation (mean ± SD [mg/ml], 1.4 ± 0.3 vs. 0.8 ± 0.4; P = 0.002; n = 12/11) were also lower after sevoflurane only in the wild-type mice. Chimeric mice showed the required expression of the adenosine A2B receptor on the hematopoietic and nonhematopoietic compartments for the protective effects of the anesthetic. Sevoflurane induced the expression of hypoxia-inducible factor 1α and adenosine A2B receptor in the intestine, liver, and lung. CONCLUSIONS: Sevoflurane exerts various protective effects in two murine peritonitis-induced sepsis models. These protective effects were linked with a functional adenosine A2B receptor.


Assuntos
Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Peritonite/complicações , Receptor A2B de Adenosina/efeitos dos fármacos , Sepse/etiologia , Sepse/prevenção & controle , Sevoflurano/farmacologia , Transdução de Sinais/efeitos dos fármacos , Anestésicos Inalatórios/farmacologia , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL
13.
J Int Med Res ; 49(4): 3000605211005936, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33906525

RESUMO

OBJECTIVE: Previous studies suggested that sevoflurane exerts anti-proliferative, anti-migratory, and anti-invasive effects on cancer cells. To determine the role of sevoflurane on gastric cancer (GC) progression, we evaluated its effects on the proliferation, migration, and invasion of SGC7901, AGS, and MGC803 GC cells. METHODS: GC cells were exposed to different concentrations of sevoflurane (1.7, 3.4, or 5.1% v/v). Cell viability, migration, and invasion were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assays. Immunohistochemical staining and immunoblotting were performed to analyze forkhead box protein 3 (FOXP3) protein expression in tissue specimens and cell lines, respectively. RESULTS: FOXP3 was downregulated in human GC specimens and cell lines. Functionally, FOXP3 overexpression significantly inhibited the proliferation, migration, and invasion of GC cells and accelerated their apoptosis. Moreover, sevoflurane significantly blocked GC cell migration and invasion compared with the findings in the control group. However, FOXP3 silencing neutralized sevoflurane-induced apoptosis and the inhibition of GC cell migration and invasion. Sevoflurane-induced apoptosis and the suppression of migration and invasion might be associated with FOXP3 overactivation in GC cells. CONCLUSIONS: Sevoflurane activated FOXP3 and prevented GC progression via inhibiting cell migration and invasion in vitro.


Assuntos
Neoplasias Gástricas , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Sevoflurano/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética
14.
Biochem Biophys Res Commun ; 557: 254-260, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-33894411

RESUMO

Isoflurane and sevoflurane are volatile anesthetics (VA) widely used in clinical practice to provide general anesthesia. We and others have previously shown that VAs have immunomodulatory effects and may have a significant impact on the progression of disease states. Flagellin is a component of Gram negative bacteria and plays a significant role in the pathophysiology of bacterial pneumonia through its binding to Toll-like Receptor 5 (TLR5). Our results showed that VAs, not an intravenous anesthetic, significantly attenuated the activation of TLR5 and the release of the neutrophil chemoattractant IL-8 from lung epithelial cells. Furthermore, flagellin-induced lung injury was significantly attenuated by VAs by inhibiting neutrophil migration to the bronchoalveolar space. The lungs of cystic fibrosis (CF) patients are highly colonized by Pseudomonas aeruginosa, which causes inflammation. The retrospective study of oxygenation in patients with CF who had received VA versus intravenous anesthesia suggested that VAs might have the protective effect for gas exchange. To understand the interaction between VAs and TLR5, a docking simulation was performed, which indicated that isoflurane and sevoflurane docked into the binding interphase between TLR5 and flagellin.


Assuntos
Anestésicos Inalatórios/farmacologia , Fibrose Cística/microbiologia , Células Epiteliais/efeitos dos fármacos , Flagelina/toxicidade , Inflamação/prevenção & controle , Pulmão/efeitos dos fármacos , Infecções por Pseudomonas/tratamento farmacológico , Receptor 5 Toll-Like/metabolismo , Anestésicos Inalatórios/química , Animais , Linhagem Celular Tumoral , Fibrose Cística/complicações , Células Epiteliais/metabolismo , Feminino , Flagelina/química , Humanos , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-8/metabolismo , Isoflurano/química , Isoflurano/farmacologia , Pulmão/metabolismo , Pulmão/microbiologia , Pulmão/patologia , Masculino , Camundongos , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/metabolismo , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/imunologia , Estudos Retrospectivos , Sevoflurano/química , Sevoflurano/farmacologia , Receptor 5 Toll-Like/química , Receptor 5 Toll-Like/genética
15.
Biochem Biophys Res Commun ; 553: 65-71, 2021 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-33756347

RESUMO

Sevoflurane anesthesia in pregnant mice could induce neurotoxicity in the developing brain and disturb learning and memory in the offspring mice. Whether it could impair social behaviors in the offspring mice is uncertain. Therefore, we assessed the neurobehavioral effect of in-utero exposure to sevoflurane on social interaction behaviors in C57BL/6 mice. The pregnant mice were anesthetized with 2.5% sevoflurane in 100% oxygen for 2 h, and their offspring mice were tested in three-chambered social paradigm, which includes three 10-min sessions of habituation, sociability, and preference for social novelty. At the juvenile age, the offspring mice showed abnormal sociability, as proved by not taking more time sniffing at the stranger 1 mouse compared with the empty enclosure (108.5 ± 25.4 vs. 108.2 ± 44.0 s, P = 0.9876). Meanwhile, these mice showed impaired preference for social novelty, as evidenced by not taking more time sniffing at the stranger 2 compared with the stranger 1 mouse (92.1 ± 52.2 vs. 126.7 ± 50.8 s, P = 0.1502). At the early adulthood, the offspring mice retrieved the normal sociability (145.6 ± 33.2 vs. 76.0 ± 31.8 s, P = 0.0001), but remained the impaired preference for social novelty (100.6 ± 29.3 vs. 118.0 ± 47.9 s, P = 0.3269). Collectively, these results suggested maternal anesthesia with sevoflurane could induce social interaction deficits in their offspring mice. Although the disturbance of sociability could be recoverable, the impairment of preference for social novelty could be long-lasting.


Assuntos
Anestésicos Inalatórios/farmacologia , Mães , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Sevoflurano/farmacologia , Comportamento Social , Interação Social/efeitos dos fármacos , Envelhecimento , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/embriologia , Encéfalo/patologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Fatores de Tempo
16.
Life Sci ; 274: 119327, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33711390

RESUMO

This study aimed to explore the potential target of the cardio-protective effect induced by sevoflurane anesthesia based on evidence from clinical samples and in vitro model. Forty patients undergoing mitral valve replacement were randomly allocated to receive sevoflurane or propofol-based anesthesia. Atrial muscle specimens were collected from all patients, of which 5 were used to perform transcriptomics analysis. The cTn-I concentration was tested before, at the end of, and 24 h after surgery. In in vitro study, the expression level of the identified target gene, i.e., THAP11, was studied in H9C2 cells treated with sevoflurane or propofol. Then, we studied cell viability using CCK-8 staining, apoptosis by using flow cytometry, and cell death by lactic acid dehydrogenase (LDH) detection in H9C2 cells exposed to oxygen glucose deprivation/reoxygenation (OGD/R) injury. THAP11 was the most significantly down-regulated gene in the transcriptomics analysis (P < 0.001), as confirmed in validation samples (P = 0.006). THAP11 mRNA levels in atrial muscle specimens were positively associated with cTn-I levels at 24-h postoperatively (determination coefficient = 0.564; P < 0.001). Sevoflurane treatment down-regulated THAP11 in H9C2 cell models, which promoted cell viability, inhibited cell apoptosis, and death in the OGD/R injury cell model. Up-regulation of THAP11 reduced the protective effect of sevoflurane treatment against OGD/R injury. Sevoflurane anesthesia down-regulates the expression of THAP11, which contributes to a cardio-protective effect. THAP11 down-regulation promotes cell viability, and inhibits cell apoptosis and death, thereby protecting again myocardial injury; it may therefore be a novel target for perioperative cardio-protection.


Assuntos
Cardiotônicos/farmacologia , Insuficiência da Valva Mitral/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Proteínas Repressoras/antagonistas & inibidores , Sevoflurano/farmacologia , Anestésicos Inalatórios/farmacologia , Animais , Apoptose , Sobrevivência Celular , Regulação para Baixo , Feminino , Glucose/deficiência , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/metabolismo , Insuficiência da Valva Mitral/patologia , Traumatismo por Reperfusão Miocárdica/etiologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Oxigênio/metabolismo , Ratos , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo
17.
Life Sci ; 275: 119391, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33774026

RESUMO

Sevoflurane (Sev) has protective effects in acute lung injury (ALI), but the relevant mechanisms are still not fully understood. The present study aimed to determine whether Sev exerts a protective effect on lipopolysaccharide (LPS)-induced ALI by regulating ferroptosis. In this study, we found that Sev could protect mice from lung injury caused by LPS stimulation, including extenuating lung histological damage, pulmonary edema and pulmonary vascular permeability, and the content of inflammatory factors in Bronchoalveolar lavage fluid (BALF), as well as improving the survival rate of ALI mice, which was in line with the effects of ferroptosis inhibitor ferrostatin-1. Simultaneously, Sev could eliminate the worsening effects of ferroptosis inducer Fe-citrate on LPS-induced ALI to a certain extent. Additionally, the administration of Sev could inhibit ferroptosis caused by LPS, which was manifested by reducing the accumulation of MDA and Fe2+, and increasing the levels of GSH and GPX4 in the lung tissues of ALI mice. It was also observed in BEAS-2B cells that the increased MDA and Fe2+ levels and the decreased GSH and GPX4 levels caused by LPS could be rescued by ferrostatin-1 and Sev. LPS stimulation compensatory up-regulated heme oxygenase-1 (HO-1) expression in mouse lung tissues and BEAS-2B cells, which could be enhanced by Sev. Moreover, HO-1 depletion could offset the inhibitory effect of Sev on LPS-induced ferroptosis and inflammation in BEAS-2B cells. Taken together, Sev inhibited ferroptosis by up-regulating HO-1 expression to reduce LPS-induced ALI, which may provide a possible mechanism for the application of Sev in clinical anesthesia.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Ferroptose/efeitos dos fármacos , Lipopolissacarídeos/efeitos adversos , Sevoflurano/farmacologia , Lesão Pulmonar Aguda/patologia , Animais , Western Blotting , Linhagem Celular , Humanos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/patologia , Sevoflurano/uso terapêutico
18.
Int J Mol Sci ; 22(4)2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33673181

RESUMO

Inhalational anaesthetics were previously reported to promote ovarian cancer malignancy, but underlying mechanisms remain unclear. The present study aims to investigate the role of sevoflurane- or desflurane-induced microRNA (miRNA) changes on ovarian cancer cell behaviour. The cultured SKOV3 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 h. Expression of miR-138, -210 and -335 was determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and Cell Counting Kit-8 (CCK8) assay with or without mimic miR-138/-210 transfections. The miRNA downstream effector, hypoxia inducible factor-1α (HIF-1α), was also analysed with immunofluorescent staining. Sevoflurane or desflurane exposure to cancer cells enhanced their proliferation and migration. miR-138 expression was suppressed by both sevoflurane and desflurane, while miR-210 expression was suppressed only by sevoflurane. miR-335 expression was not changed by either sevoflurane or desflurane exposure. The administration of mimic miR-138 or -210 reduced the promoting effects of sevoflurane and desflurane on cancer cell proliferation and migration, in line with the HIF-1α expression changes. These data indicated that inhalational agents sevoflurane and desflurane enhanced ovarian cancer cell malignancy via miRNA deactivation and HIF-1α. The translational value of this work needs further study.


Assuntos
Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Desflurano/farmacologia , Regulação para Baixo/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MicroRNAs/biossíntese , Neoplasias Ovarianas/metabolismo , RNA Neoplásico/biossíntese , Sevoflurano/farmacologia , Linhagem Celular Tumoral , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Ovarianas/patologia
19.
Mol Med Rep ; 23(6)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33786635

RESUMO

Poor prognosis in patients with glioma is primarily due to rapid tumor growth and cell invasion and migration. In addition, microRNA (miR)­27b is decreased in metastatic glioma. The present study investigated whether sevoflurane inhibited glioma cell progression by targeting miR­27b. Cell proliferation was analyzed using a Cell Counting Kit­8 assay and a wound healing assay was used to detect cell migration. Western blotting and reverse transcription­quantitative PCR analysis were performed to determine the protein and mRNA expression levels. A dual luciferase assay was used to determine the relationship between vascular epithelial growth factor (VEGF) and miR­27b. VEGF was identified to be a direct target of miR­27b. Moreover, sevoflurane treatment increased the expression of miR­27b and decreased the expression of VEGF in U251 and U87 cells. Compared with the control group, sevoflurane inhibited the proliferation and migration of U251 and U87 cells, as well as the expression of matrix metalloproteinase (MMP)­2 and MMP­9, which were subsequently abolished by pre­treatment with an miR­27b inhibitor. The present results indicated the potential use of sevoflurane by anesthesiologists for the surgical resection of glioma, which may improve patient outcomes in the clinical setting.


Assuntos
Antineoplásicos/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Glioma/metabolismo , Sevoflurano/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
20.
Anticancer Drugs ; 32(5): 537-547, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33735116

RESUMO

Colorectal cancer (CRC) is a common malignancy. Sevoflurane has been reported to involve in the progression in several cancers. However, the molecular mechanism of sevoflurane in CRC progression remains unclear. Quantitative real-time PCR and western blot was used to detect the expression of miR-637 and WNT1. Cell migration, invasion and apoptosis were detected by transwell assay, flow cytometry or western blot, respectively. The interaction between WNT1 and miR-637 was confirmed by luciferase reporter assay, RNA immunoprecipitation assay and pull-down assay. We found sevoflurane could inhibit cell migration and invasion but induced apoptosis in CRC. Besides, the miR-637 level was decreased in CRC tissues and cells but could be rescued by sevoflurane. MiR-637 overexpression enhanced the anticancer functions of sevoflurane in CRC cells, while miR-637 inhibition showed opposite effects. WNT1 was confirmed to be a target of miR-637 and was inhibited by sevoflurane or miR-637. Importantly, knockdown of WNT1 reversed the carcinogenic effects mediated by miR-637 inhibitor in CRC cells treated with sevoflurane. Collectively, sevoflurane inhibited cell migration, invasion and induced apoptosis by regulating the miR-637/WNT1 axis in colorectal cancer, indicating a novel insight into the effective clinical implication for the anesthetic in CRC treatment.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , MicroRNAs/biossíntese , Sevoflurano/farmacologia , Proteína Wnt1/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , Reação em Cadeia da Polimerase em Tempo Real
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