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1.
Biosci Biotechnol Biochem ; 84(1): 187-197, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31566092

RESUMO

Walnut is a nutritious food material, but only a few studies have been conducted on the mechanisms of its functions and the technique for quality evaluation. Therefore, we analyzed the components in aqueous methanol extract of walnut, and characterized 30 components, including three new compounds, glansreginin C, ellagic acid 4-O-(3'-O-galloyl)-ß-D-xyloside, and platycaryanin A methyl ester. We analyzed the extracts of other nuts using HPLC and clarified that a characteristic peak corresponding to glansreginin A was mainly observed in walnut. These results suggested that glansreginin A might be an indicator component of the quality of walnut. We then examined whether glansreginin A has neuroprotective effect, using lipopolysaccharide (LPS)-induced inflammatory model mice. The results revealed that oral administration of glansreginin A prevented LPS-induced abnormal behavior and LPS-induced hyper-activation of microglia in the hippocampus. These results suggested that glansreginin A has the ability to exert neuroprotective effect via anti-inflammation in the brain.


Assuntos
Anti-Inflamatórios/farmacologia , Juglans/química , Fármacos Neuroprotetores/farmacologia , Valor Nutritivo , Extratos Vegetais/farmacologia , Quinolinas/farmacologia , Quinolonas/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Ácido Elágico/farmacologia , Hipocampo/patologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Lipopolissacarídeos/farmacologia , Masculino , Metanol/química , Éteres Metílicos/farmacologia , Camundongos , Camundongos Endogâmicos ICR , Microglia/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Quinolinas/uso terapêutico
2.
Bratisl Lek Listy ; 120(12): 887-893, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31855046

RESUMO

OBJECTIVE: We aimed to investigate the effects of recurrent sevoflurane anesthesia on cognitive functions in Alzheimer Disease. MATERIALS AND METHODS: Rats were divided into 4 groups as followed: control (Group C), sevoflurane (Group S), Alzheimer's (Group A) and Alzheimer's + sevoflurane (Group AS)]. Cognitive functions were evaluated with Radial Arm Maze Test (RAMT). Alzheimer model was created by administering 3 mg/kg (10 µl) STZ. Sevoflurane was administered to S and AS groups. Serum samples and hippocampus tissues were analyzed. RESULTS: In RAM test, the entry-exit data were significantly decreased in A and AS groups. After the 2nd and 3rd administration of anesthesia, the numbers were significantly decreased in Group S. Glial-fibrillary-acidic protein levels were significantly higher in AS compared to the C and S groups. The brain tissue caspase 3 activity was less than 1% in all rats in the Group C, 3 % in 2 rats and 1 % in 1 rat in the Group AS. In A and AS group, serum catalase, myeloperoxidase and ferroxidase activities were found to be higher than in the other groups and myeloperoxidase activity was higher in the AS than in the A Group. Serum native thiol, total thiol and disulfide levels were found to be significantly different in the A and AS groups. CONCLUSION: Sevoflurane anesthesia negatively affected the cognitive functions (Tab. 5, Fig. 10, Ref. 51).


Assuntos
Doença de Alzheimer/induzido quimicamente , Anestesia , Anestésicos Inalatórios , Cognição/efeitos dos fármacos , Éteres Metílicos/farmacologia , Sevoflurano/efeitos adversos , Estreptozocina/farmacologia , Animais , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Sevoflurano/administração & dosagem
3.
J Appl Microbiol ; 127(5): 1468-1478, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31403229

RESUMO

AIMS: Medicinal plant-associated endophytic fungi are important sources of precious bioactive compounds, contributing more than 80% of the natural drugs for various ailments. The present study was aimed at evaluating the anticancer activity of the crystallized compound alternariol methyl ether (AME) against hepatocellular carcinoma (HCC) both in vitro and in vivo from an endophytic fungus residing in the medicinal plant Vitex negundo. METHODS AND RESULTS: The secondary metabolites from the endophytic fungus Alternaria alternata MGTMMP031 were isolated. Purification and characterization of the compound was performed and the potential compound was identified as AME. The crystal structure of AME was unambiguously confirmed by X-ray analysis. AME has been checked for its antibacterial and anticancer properties which showed its effectiveness against various bacteria and demonstrated marked anti-proliferative activity against the human HCC cells (HUH-7) both in vitro and in vivo. Mode of actions included cell cycle arrest, reducing the level of markers enzymes of liver cancer and preventing tumour growth. CONCLUSIONS: Alternariol methyl ether acts as a potential therapeutic target against HCC. The compound was isolated and the crystal structure was obtained for the first time from the endophytic fungus A. alternata MGTMMP031. In the present study, the crystallized structure of AME was obtained by slow evaporation technique. It can be concluded that AME acts as a potential therapeutic target against HCC. SIGNIFICANCE AND IMPACT OF THE STUDY: Endophytic fungi residing in the medicinal plants have strong biological significance and bioactive compounds from these fungi provide better therapeutic targets against diseases.


Assuntos
Alternaria/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Endófitos/química , Lactonas/isolamento & purificação , Lactonas/farmacologia , Éteres Metílicos/química , Plantas Medicinais/microbiologia , Alternaria/isolamento & purificação , Alternaria/metabolismo , Antineoplásicos/isolamento & purificação , Antineoplásicos/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/fisiopatologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Cristalização , Endófitos/isolamento & purificação , Endófitos/metabolismo , Humanos , Lactonas/química , Lactonas/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/fisiopatologia , Éteres Metílicos/isolamento & purificação , Éteres Metílicos/farmacologia , Metabolismo Secundário
4.
Brain Res Bull ; 144: 140-148, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30217735

RESUMO

Sevoflurane is an experimental potent yet volatile anesthesia agent characterized by a low blood/gas partition coefficient. However, exposure to sevoflurane in neonatal mice has been speculated to result in learning deficits and abnormal social behavior. The aim of the present study was to investigate the relationship between sevoflurane and miR-96, in an attempt to identify the means by which it mediates IGF1R to influence the cognitive dysfunction (CD) in neonatal rats. Relationship between differentially expressed miRNAs and sevoflurane concentration was identified. The potential underlying regulatory mechanisms involved with sevoflurane were investigated through the administration of varying concentrations of the agent (1%, 2% and 4%), combined with miR-96 mimic or an inhibitor. A target prediction program was utilized, while the luciferase activity was determined in order to verify whether miR-96 targets IGF1R. The mRNA and protein levels of IGF1R, Bcl-2, Bax, and caspase-3 were measured followed by the determination of hippocampal neuron apoptosis. Learning and memory performance was assessed using the Morris water maze (MWM) test and step-down test. The obtained results highlighted a positive correlation between miR-96 and the concentration of sevoflurane, while miR-96 was confirmed to negatively target IGF1R. Our analyses indicated that 4% sevoflurane had a significantly stronger effect on reducing the levels of IGF1R and Bcl-2, while elevating the levels of miR-96, Bax and caspase-3 more so than that of 1% or 2% sevoflurane, which resulted in increased hippocampal neuron apoptosis but diminished the learning and memory performance of the rats. The addition of miR-96 mimic was demonstrated to exacerbate the influence of sevoflurane on hippocampal neurons as well as the cognitive function of the rats. The key findings of our study highlighted the role of miR-96 in the potential mechanism of sevoflurane anesthesia-induced CD in neonatal rats through the downregulation of IGF1R.


Assuntos
Cognição/efeitos dos fármacos , Disfunção Cognitiva/genética , MicroRNAs/metabolismo , Anestésicos Inalatórios/farmacologia , Animais , Animais Recém-Nascidos/genética , Apoptose/efeitos dos fármacos , Disfunção Cognitiva/induzido quimicamente , Feminino , Hipocampo/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Éteres Metílicos/farmacologia , MicroRNAs/genética , Neurônios/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptor IGF Tipo 1/antagonistas & inibidores , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Sevoflurano/farmacologia
5.
Cell Physiol Biochem ; 49(4): 1476-1491, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30205407

RESUMO

BACKGROUND/AIMS: Long non-coding RNA (lncRNA) and glucagon-like peptide 1 receptor (GLP-1R) are crucial for heart development and for adult heart structural maintenance and function. Herein, we performed a study to explore the effect of lncRNA LINC00652 (LINC00652) on myocardial ischemia-reperfusion (I/R) injury by targeting GLP-1R through the cyclic adenosine monophosphate-protein kinase A (cAMP/PKA) pathway. METHODS: Bioinformatics software was used to screen the long-chain non-coding RNAs associated with myocardial ischemia-reperfusion and to predict target genes. The mRNA and protein levels of LINC00652, GLP-1R and CREB were detected by RT-qPCR and western blotting. In order to identify the interaction between LINC00652 and myocardial I/R injury, the cardiac function, the hemodynamic changes, the pathological changes of the myocardial tissues, the myocardial infarct size, and the apoptosis of myocardial cells of mice were measured. Meanwhile, the levels of serum IL-1ß and TNF-α were detected. RESULTS: LINC00652 was overexpressed in the myocardial cells of mice with myocardial I/R injury. GLP-1R is the target gene of LINC00652. We also determined higher levels of LINC00652 and GLP-1R in the I/R modeled mice. Additionally, si-LINC00652 decreased cardiac pathology, infarct size, apoptosis rates of myocardial cells, and levels of IL-1ß and TNF-α, and increased GLP-1R expression cardiac function, normal hemodynamic index, and the expression and phosphorylation of GLP-1R and CREB proteins. CONCLUSION: Taken together, our key findings of the present highlight LINC00652 inhibits the activation of the cAMP/PKA pathway by targeting GLP-1R to reduce the protective effect of sevoflurane on myocardial I/R injury in mice.


Assuntos
Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Éteres Metílicos/farmacologia , RNA Longo não Codificante/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regiões 3' não Traduzidas , Animais , Apoptose/efeitos dos fármacos , AMP Cíclico/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Modelos Animais de Doenças , Receptor do Peptídeo Semelhante ao Glucagon 1/antagonistas & inibidores , Receptor do Peptídeo Semelhante ao Glucagon 1/genética , Hemodinâmica/efeitos dos fármacos , Interleucina-1beta/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Sevoflurano
6.
Life Sci ; 209: 34-42, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-30071197

RESUMO

AIMS: The development of central nervous system requires proliferation of neural stem cells followed by differentiation. Cell cycle parameters are closely related with cell fate specification and differentiation. Recent researches indicated that wnt/ß-catenin signaling pathway might cause proliferation inhibition and differentiation abnormality through interfering NSCs cell cycle. Our previous research also showed that multiple sevoflurane exposure to neural stem cells inhibited proliferation via repressing transcription factor Pax6 and cyclin D1 through inhibiting wnt/ß-catenin pathway. All above encouraged us to figure out the effect of sevoflurane on cell cycle and neurogenesis. MAIN METHODS: Primary mouse cultured neural stem cells were used and exposed to 4.1% sevoflurane for 6 h in this study. The expression of ß-catenin, GSK-3ß, c-myc and cyclin D1 were determined by western blot and qRT-PCR. FACS was used to measure the cell cycle. The proliferation of NSCs was evaluated by EdU staining while the differentiation was evaluated by Tuj1 and GFAP staining on immunocytochemistry. KEY FINDINGS: We found that exposure to sevoflurane at a concentration of 4.1% for 6 h induced inhibition of wnt/ß-catenin pathway, cell cycle arrest at G0/G1 phase and an earlier switch from proliferation to differentiation. GSK-3ß specific inhibitor, CHIR99021, attenuated sevoflurane-induced cell cycle arrest and abnormality of neurogenesis in neural stem cells. SIGNIFICANCE: Our research suggested that sevoflurane arrested cell cycle at G0/G1 phase through inhibition of wnt/ß-catenin signaling pathway thus resulting in a premature differentiation in NSCs. This study presents a deeper understanding of the mechanism on cognitive impairment by sevoflurane exposure.


Assuntos
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Éteres Metílicos/farmacologia , Células-Tronco Neurais/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Proteínas Wnt/antagonistas & inibidores , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/antagonistas & inibidores , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Sevoflurano , Proteínas Wnt/metabolismo , beta Catenina/metabolismo
7.
Vet J ; 238: 63-69, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30103917

RESUMO

The effects of pre-treatment with vatinoxan (MK-467) on dexmedetomidine-induced cardiopulmonary alterations were investigated in sheep. In a crossover study design with a 20-day washout, seven sheep were anaesthetised with sevoflurane in oxygen and air. The sheep were ventilated with the pressure-limited volume-controlled mode and a positive end-expiratory pressure of 5cmH2O. Peak inspiratory pressure (PIP) was set at 25cmH2O. The sheep received either 150µg/kg vatinoxan HCl (VAT+DEX) or saline intravenously (IV) 10min before IV dexmedetomidine HCl (3µg/kg, DEX). Cardiopulmonary variables were measured before treatments (baseline), 3min after vatinoxan or saline, and 5, 15 and 25min after dexmedetomidine. Computed tomography (CT) of lung parenchyma was performed at baseline, 2min before dexmedetomidine, and 10, 20 and 30min after DEX. Bronchoalveolar lavage (BAL) was performed after the last CT scan and shortly before sheep recovered from anaesthesia. After VAT, cardiac output significantly increased from baseline. DEX alone significantly decreased partial arterial oxygen tension, total dynamic compliance and tidal volume, whereas PIP was significantly increased. With VAT+DEX, these changes were minimal. No significant changes were detected in haemodynamics from baseline after DEX. With VAT+DEX, mean arterial pressure and systemic vascular resistance were significantly decreased from baseline, although hypotension was not detected. On CT, lung density was significantly increased with DEX as compared to baseline. No visual abnormalities were detected in bronchoscopy and no differences were detected in the BAL fluid after either treatment. The pre-administration of vatinoxan alleviates dexmedetomidine-induced bronchoconstriction, oedema and hypoxaemia in sevoflurane-anaesthetised sheep.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Débito Cardíaco/efeitos dos fármacos , Complacência Pulmonar/efeitos dos fármacos , Anestésicos Inalatórios/administração & dosagem , Animais , Pressão Sanguínea/efeitos dos fármacos , Estudos Cross-Over , Dexmedetomidina/farmacologia , Frequência Cardíaca , Éteres Metílicos/farmacologia , Oxigênio/metabolismo , Mecânica Respiratória/efeitos dos fármacos , Sevoflurano , Ovinos , Doenças dos Ovinos/prevenção & controle
8.
Neurosci Lett ; 685: 160-166, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30157449

RESUMO

Severe hemorrhagic shock induces cognitive dysfunction by promoting cell death mediated by activating endoplasmic reticulum (ER) stress. Sevoflurane postconditioning prevents neuronal apoptosis against cerebral ischemia/reperfusion injury. It is unknown if this protective effect on hemorrhagic shock and resuscitation rats (HSR) is associated with ER stress attenuation. Male adult Sprague-Dawley rats were subjected HSR by removing 40% blood volume within 30 min, and 60 min later the animals were resuscitated with infusion of the removing blood in 30 min. Sevoflurane postconditioning was performed by inhaling sevoflurane at three different concentrations (0.5, 1.0, 1.5 MAC) at the onset of resuscitation for 30 min. Severe hypotension (mean arterial pressure 40-45 mmHg) occurred in the shock session for 60 min accompanying with significantly elevated lactate, decreased BE and pH values in arterial blood gas analysis. There were impaired spatial learning and memory following HSR indicated by persistently longer escape latency and lower correct rate, as well as less duration and crossing in the target quadrant by using Morris water maze and Y-maze tests. In the hippocampal CA1 region, there was significantly higher activity of caspase-3 induced by HSR. HSR also elevated the expression of inositol-requiring enzyme 1α (IRE1α) and caspase-12 in the hippocampus by western blot analysis. Sevoflurane postconditioning at 1.0 and 1.5 MAC significantly reversed these changes. These findings suggested that sevoflurane postconditioning could improve spatial learning and memory deficits induced by severe hemorrhagic shock and subsequent resuscitation. The suppression of endoplasmic reticulum stress provided critical contribution in neural apoptosis mediated by IRE1α-caspase-12 pathway.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Endorribonucleases/efeitos dos fármacos , Memória/efeitos dos fármacos , Complexos Multienzimáticos/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/efeitos dos fármacos , Sevoflurano/farmacologia , Aprendizagem Espacial/efeitos dos fármacos , Animais , Caspase 12/efeitos dos fármacos , Pós-Condicionamento Isquêmico/métodos , Masculino , Éteres Metílicos/farmacologia , Fármacos Neuroprotetores/farmacologia , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Choque Hemorrágico/tratamento farmacológico
9.
Mol Med Rep ; 18(3): 2923-2928, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30015951

RESUMO

The aim of the present study was to investigate the potential role of club cell secretory protein (CCSP), an endogenous modulator, in reducing pulmonary inflammation induced by sevoflurane following one­lung ventilation (OLV). Healthy Japanese white rabbits were randomly assigned to six groups: Sham­operated group (group S); respiratory management of OLV group (group O); OLV + sevoflurane treated group (group OF), club cells exfoliated + sham­operated group (group NA), club cells exfoliated + OLV group (group NAO); and club cells exfoliated + OLV + sevoflurane treated group (group NAOF). At the end of the experimental observation, all animals in the different groups were sacrificed and lung injury was evaluated according to the lung wet/dry weight ratio and histological scoring system. Lung homogenates were harvested to detect the mRNA and protein expression of cytosolic phospholipase A2 (c­PLA2) and CCSP. The content of arachidonic acid was measured using an ELISA. Following OLV treatment, c­PLA2 expression was increased, CCSP expression was decreased and lung injury scores were significantly increased. Sevoflurane inhalation in the OLV­treated group induced an upregulation of CCSP and a downregulation of c­PLA2 expression. In the group NAO, in which the club cells were simultaneously exfoliated, OLV caused more severe lung damage and induced higher expression of c­PLA2 compared with that in group O. However, sevoflurane inhalation reduced the extent of lung injury and the expression of c­PLA2, even when the endogenous modulator of lung inflammation, CCSP, was exfoliated (group NAOF). These results indicated that OLV promoted lung inflammation through the CCSP and c­PLA2 pathway. However, the results from the club cells exfoliated group indicated that the CCSP may not be involved in the protective effect exerted by sevoflurane inhalation.


Assuntos
Anti-Inflamatórios/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Éteres Metílicos/farmacologia , Fosfolipases A2 Citosólicas/genética , Lesão Pulmonar Induzida por Ventilação Mecânica/genética , Animais , Ácido Araquidônico/metabolismo , Biópsia , Modelos Animais de Doenças , Feminino , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Fosfolipases A2 Citosólicas/metabolismo , Coelhos , Sevoflurano , Uteroglobina/genética , Uteroglobina/metabolismo , Lesão Pulmonar Induzida por Ventilação Mecânica/tratamento farmacológico , Lesão Pulmonar Induzida por Ventilação Mecânica/metabolismo , Lesão Pulmonar Induzida por Ventilação Mecânica/patologia
10.
Med Sci Monit ; 24: 4982-4991, 2018 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-30018280

RESUMO

BACKGROUND Collapsin response mediator protein-2 (CRMP-2) is the first member of the CRMP family that has been identified in primary neuronal cells; it was originally found and identified in the regulation of microtubule dimerization into microtubules. MATERIAL AND METHODS In the present study, we aimed to investigate the roles and mechanisms of CRMP-2 in sevoflurane-induced neurocyte injury. Cell viability, proliferation, and apoptosis were measured by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Colorimetry was performed to measure the activity of caspase-3. Western blot and quantitative real-time reverse transcription assays were used to evaluate the related mRNAs and proteins expression. RESULTS We found that CRMP-2 reversed the inhibitory effect of sevoflurane on the viability of nerve cells. Moreover, CRMP-2 accelerated the proliferation and suppressed the apoptosis of sevoflurane-induced nerve cells. CRMP-2 modulated the expression levels of apoptosis-associated protein in sevoflurane-induced nerve cells. Furthermore, it was demonstrated that CRMP-2 impacted the PI3K-mTOR-S6K pathway. CONCLUSIONS CRMP2 ameliorated sevoflurane-mediated neurocyte injury by targeting the PI3K-mTOR-S6K pathway. Thus, CRMP2 might be an effective target for sevoflurane-induced neurocyte injury therapies.


Assuntos
Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Traumatismos dos Nervos Cranianos/tratamento farmacológico , Feminino , Hipocampo/efeitos dos fármacos , Éteres Metílicos/farmacologia , Proteínas do Tecido Nervoso/farmacologia , Neurônios/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Gravidez , Ratos , Ratos Sprague-Dawley , Proteínas Quinases S6 Ribossômicas/metabolismo , Sevoflurano , Serina-Treonina Quinases TOR/metabolismo
11.
Vet Anaesth Analg ; 45(4): 487-495, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29880279

RESUMO

OBJECTIVE: To determine sevoflurane's minimum alveolar concentration (MACSEVO) and its cardiopulmonary effects in sheep. STUDY DESIGN: Prospective experimental study. ANIMALS: A group of 10 female nonpregnant Sardinian milk sheep. METHODS: Anesthesia was induced in each sheep twice with sevoflurane in oxygen. After a 30 minute equilibration at end-tidal sevoflurane concentration (Fe'Sevo) of 2.8%, an electrical stimulus (5 Hz/1 ms/50 mA) was applied to the right thoracic limb for 1 minute or until gross purposeful movement occurred. The Fe'Sevo was then changed using a 0.2% up-and-down protocol, dependent on whether or not the response was positive, and then noxious stimulation was repeated. The MACSEVO was defined as the mean Fe'Sevo between that allowing purposeful movement and that not. The group of 10 sheep were re-anesthetized and MACSEVO was re-determined. Thereafter, Fe'Sevo was maintained for 15 minutes each at concentrations corresponding to 1.0, 1.3, 1.6, 1.9 and 0.75 MACSEVO multiples, and cardiopulmonary, blood gas, acid-base variables and plasma electrolytes were determined. Also, time to induction of anesthesia, extubation and recovery were recorded. RESULTS: The mean ± standard deviation of the MACSEVO was 2.74 ± 0.38%. Median (interquartile range) time to intubation was 3.13 (2.98-3.33) minutes, time to extubation was 6.85 ± 2.65 minutes and time to recovery was 13.4 ± 5.2 minutes. With increasing Fe'Sevo, arterial blood pressures progressively decreased as did minute ventilation, which in turn caused end-tidal carbon dioxide, arterial partial pressure of carbon dioxide and bicarbonate values to steadily increase without significantly affecting arterial partial pressure of oxygen. CONCLUSIONS AND CLINICAL RELEVANCE: The reported MACSEVO agrees with published data in this and other species. Administration of sevoflurane in sheep caused marked hemodynamic and respiratory depression, but soon after turning off the vaporizer, sheep could be extubated and recovered rapidly and event-free.


Assuntos
Anestésicos Inalatórios/farmacologia , Éteres Metílicos/farmacologia , Alvéolos Pulmonares/química , Anestesia por Inalação/métodos , Anestesia por Inalação/veterinária , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/análise , Animais , Gasometria/veterinária , Relação Dose-Resposta a Droga , Feminino , Hemodinâmica/efeitos dos fármacos , Éteres Metílicos/administração & dosagem , Éteres Metílicos/análise , Respiração/efeitos dos fármacos , Sevoflurano , Ovinos
12.
Mol Med Rep ; 18(1): 455-460, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29750301

RESUMO

Rapid proliferation is one of the critical characteristics of breast cancer. However, the underlying regulatory mechanism of breast cancer cell proliferation is largely unclear. The present study indicated that sevoflurane, one of inhalational anesthetics, could significantly suppress breast cancer cell proliferation by arresting cell cycle at G1 phase. Notably, the rescue experiment indicated that miR-203 was upregulated by sevoflurane and mediated the function of sevoflurane on suppressing the breast cancer cell proliferation. The present study indicated the function of the sevoflurane/miR-203 signaling pathway on regulating breast cancer cell proliferation. These results provide mechanistic insight into how the sevoflurane/miR-203 signaling pathway supresses proliferation of breast cancer cells, suggesting the sevoflurane/miR-203 pathway may be a potential target in the treatment of breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Éteres Metílicos/farmacologia , MicroRNAs/biossíntese , RNA Neoplásico/biossíntese , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Feminino , Humanos , MicroRNAs/genética , RNA Neoplásico/genética , Sevoflurano , Transdução de Sinais/genética
13.
Rom J Ophthalmol ; 62(1): 34-41, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29796432

RESUMO

Our study investigated the changes produced by diabetes on the visual pathway in a Wistar rat model. The impact of diabetes at 10 weeks after intraperitoneal streptozotocin (STZ) injection was evaluated through electrophysiological methods like visual evoked potentials (VEP) and electroretinogram (ERG). VEP and ERG were recorded simultaneously under different sevoflurane anesthetic depths. In all tested concentrations, sevoflurane affected the amplitude and latency of VEP and ERG component elements. With increasing anesthetic depths, sevoflurane increased the latencies of VEP N1, P1 and N2 peaks and ERG a- and b- waves in both control and diabetic animals. On the other hand, the amplitude of VEP showed enhancement in higher concentrations of sevoflurane, contrariwise to the drop of amplitude seen in the ERG. Diabetes additionally increased the latencies of VEP peaks and decreased the N1-P1 amplitude of the VEP when compared to control at the same anesthetic depth. The a- and b- waves were also delayed by diabetes at 10 weeks post-STZ diabetic induction, with the exception of highly profound anesthetic depth in which the result for the b wave were conflicting. We found a reduction in amplitude of the a-b wave in diabetic animals, when ERG was recorded under 6% and 8% sevoflurane concentration. In conclusion, neurophysiological studies like VEP and ERG are useful in the assessment of retinal and optic nerve dysfunctions produced by diabetes, yet considering the alterations that occur during anesthesia if this is used.


Assuntos
Anestésicos Inalatórios/farmacologia , Éteres Metílicos/farmacologia , Vias Visuais/efeitos dos fármacos , Animais , Diabetes Mellitus Experimental , Eletrorretinografia , Potenciais Evocados Visuais , Ratos , Ratos Wistar , Sevoflurano
14.
Drug Des Devel Ther ; 12: 769-776, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29670333

RESUMO

Purpose: Sevoflurane preconditioning (SPC) can provide myocardial protective effects similar to ischemic preconditioning. However, the exact mechanism of SPC remains unclear. Previous studies indicate that vascular endothelial growth factor receptor 1 (VEGFR-1) is involved in ischemic preconditioning-mediated cardioprotection. This study was designed to determine the significance of VEGFR-1 signaling in SPC-mediated cardioprotection. Materials and methods: Myocardial ischemia-reperfusion (I/R) rat model was established using the Langendorff isolated heart perfusion apparatus. Additionally, after 15 min of baseline equilibration, the isolated hearts were pretreated with 2.5% sevoflurane, 2.5% sevoflurane+MF1 10 µmol/L, or 2.5% sevoflurane+placental growth factor 10 µmol/L, and then subjected to 30 min of global ischemia and 120 min of reperfusion. The changes in hemodynamic parameters, myocardial infarct size, and the levels of creatine kinase-MB, lactate dehydrogenase, cardiac troponin-I, tumor necrosis factor-α, and interleukin 6 in the myocardium were evaluated. Results: Compared to the I/R group, pretreatment with 2.5% sevoflurane significantly improved the cardiac function, limited myocardial infarct size, reduced cardiac enzyme release, upregulated VEGFR-1 expression, and decreased inflammation. In addition, the selective VEGFR-1 agonist, placental growth factor, did not enhance the cardioprotection and anti-inflammation effects of sevoflurane, while the specific VEGFR-1 inhibitor, MF1, completely reversed these effects. Conclusion: Our data have demonstrated that 2.5% sevoflurane preconditioning alleviates heart I/R injury, which is probably mediated by the anti-inflammatory property and upregulation of VEGFR-1.


Assuntos
Cardiotônicos/farmacologia , Éteres Metílicos/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Regulação para Cima/efeitos dos fármacos , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Cardiotônicos/administração & dosagem , Masculino , Éteres Metílicos/administração & dosagem , Traumatismo por Reperfusão Miocárdica/metabolismo , Ratos , Ratos Sprague-Dawley , Sevoflurano
15.
Cell Physiol Biochem ; 46(4): 1455-1470, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29689553

RESUMO

BACKGROUND/AIMS: Ischemic heart disease is a leading cause of death in cardiovascular diseases, and microRNAs (miRs) have been reported to be potential therapeutic targets in heart disease. Herein, this study aims to investigate the effects of microRNA (miR)-374 on myocardial ischemia-reperfusion (I/R) injury in rat models pretreated with sevoflurane by targeting SP1 through the PI3K/Akt pathway. METHODS: SD rats were grouped into sham, I/R and sevoflurane + I/R (sevoflurane preconditioning and I/R) groups. The biochemical indicators, pathological changes, positive expression of SP1 protein, and apoptosis rates were measured using biochemical detection, Evans blue-TTC staining, immunohistochemistry and TUNEL staining. RT-qPCR and Western blotting were used to investigate the expression of miR-374 mRNA and the protein expression of SP1, PI3K, HO-1, p53, iNOS, c-fos, Akt/p-Akt, and GSK-3ß/p-GSK-3ß. Cardiomyocytes were treated with miR-374 mimics, miR-374 inhibitors, or siRNA-SP1. Cardiomyocyte proliferation and cycle distribution and apoptosis were studied by MTT and flow cytometry. RESULTS: Compared with the I/R group, in the sevoflurane + I/R group, serum SOD and IL-10 increased, while MDA, LDH, CK, TNF-α, IL-6 and IL-10 decreased, as did the percentage of infarct area, the positive rate of SP1 and the apoptosis index. The expression of SP1, p53, iNOS and c-fos decreased, and the miR-374 expression of PI3K, HO-1, Akt/p-Akt, GSK-3ß/p-GSK-3ß increased. With the upregulation of miR-374 and the downregulation of SP1, the expression of SP1, p53, iNOS and c-fos decreased, as did the proportion of cells in G1 phase and the apoptosis rate; the expression of PI3K, HO-1, Akt/p-Akt, GSK-3ß/p-GSK-3ß increased. The results in the miR-374 inhibitor group contrasted with the above results. CONCLUSION: The results indicated that miR-374 could alleviate myocardial I/R damage in rat models pretreated with sevoflurane by targeting SP1 by activating the PI3K/Akt pathway.


Assuntos
Éteres Metílicos/farmacologia , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição Sp1/metabolismo , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Sequência de Bases , Creatina Quinase/sangue , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular , Glicogênio Sintase Quinase 3 beta/metabolismo , Heme Oxigenase-1/metabolismo , Interleucina-6/metabolismo , Pós-Condicionamento Isquêmico , Masculino , Malondialdeído/sangue , Éteres Metílicos/uso terapêutico , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Óxido Nítrico Sintase Tipo II/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Alinhamento de Sequência , Sevoflurano , Fator de Transcrição Sp1/antagonistas & inibidores , Fator de Transcrição Sp1/genética , Superóxido Dismutase/sangue , Fator de Necrose Tumoral alfa/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/efeitos dos fármacos
16.
Drug Des Devel Ther ; 12: 629-638, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29606856

RESUMO

Background: Sevoflurane post-conditioning exerts nerve-protective effects through inhibiting caspase-dependent neuronal apoptosis after a traumatic brain injury (TBI). Autophagy that is induced by the endoplasmic reticulum stress plays an important role in the secondary neurological dysfunction after a TBI. However, the relationship between autophagy and caspase-dependent apoptosis as well as the underlying nerve protection mechanism that occurs with sevoflurane post-conditioning following a TBI remains unclear. Methods: The Feeney TBI model was used to induce brain injury in rats. Evaluation of the modified neurological severity scores, measurement of brain water content, Nissl staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used to determine the neuroprotective effects of the sevoflurane post-conditioning. Both immunofluorescence and Western blot analyses were used to detect the expression of autophagy-related proteins microtubule-associated protein 1 light chain 3-II and Beclin-1, pro-apoptotic factors, as well as the activation of the phosphatidylinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway within the lesioned cortex. Results: Autophagy and neuronal apoptosis were activated in the lesioned cortex following the TBI. Sevoflurane post-conditioning enhanced early autophagy, suppressed neuronal apoptosis, and alleviated brain edema, which improved nerve function after a TBI (all P < 0.05). Sevoflurane post-conditioning induced the activation of PI3K/AKT signaling after the TBI (P < 0.05). The neuroprotective effects of sevoflurane post-conditioning were reversed through the autophagy inhibitor 3-methyladenine treatment. Conclusion: Neuronal apoptosis and the activation of autophagy were involved in the secondary neurological injury following a TBI. Sevoflurane post-conditioning weakened the TBI-induced neuronal apoptosis by regulating autophagy via PI3K/AKT signaling.


Assuntos
Apoptose/efeitos dos fármacos , Lesões Encefálicas Traumáticas/tratamento farmacológico , Éteres Metílicos/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Injeções Intraperitoneais , Masculino , Neurônios/metabolismo , Neurônios/patologia , Pentobarbital/administração & dosagem , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Sevoflurano
17.
BMC Vet Res ; 14(1): 69, 2018 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-29506576

RESUMO

BACKGROUND: The purpose of this study was to determine the effects of isoflurane, sevoflurane, propofol and alfaxalone on the canine brain metabolite bioprofile, measured with single voxel short echo time proton magnetic resonance spectroscopy at 3 Tesla. Ten adult healthy Beagle dogs were assigned to receive isoflurane, sevoflurane, propofol and alfaxalone at 3 different dose rates each in a randomized cross-over study design. Doses for isoflurane, sevoflurane, propofol and alfaxalone were FE'Iso 1.7 vol%, 2.1 vol%, 2.8 vol%, FE'Sevo 2.8 vol%, 3.5 vol% and 4.7 vol%, 30, 45 and 60 mg kg- 1 h- 1 and 10, 15 and 20 mg kg- 1 h- 1 respectively. A single voxel Point Resolved Spectroscopy Sequence was performed on a 3 T MRI scanner in three brain regions (basal ganglia, parietal and occipital lobes). Spectral data were analyzed with LCModel. Concentration of total N-acetylaspartate (tNAA), choline, creatine, inositol and glutamine and glutamate complex (Glx) relative to water content was obtained. Plasma concentration of lactate, glucose, triglycerides, propofol and alfaxalone were determined. Statistics were performed using repeated measures ANOVA or Wilcoxon Sign Rank test with alpha = 5%. RESULTS: Plasma glucose increased with isoflurane, sevoflurane and alfaxalone but decreased with propofol. Plasma lactate increased with all anesthetics (isoflurane > sevoflurane > propofol > alfaxalone). Cerebral lactate could not be detected. Only minor changes in cerebral metabolite concentrations of tNAA, choline, inositol, creatine and Glx occurred with anesthetic dose changes. CONCLUSION: The metabolomic profile detected with proton magnetic resonance spectroscopy at 3 Tesla of canine brain showed only minor differences between doses and anesthetics related to tNAA, choline, creatine, inositol and Glx.


Assuntos
Anestésicos Inalatórios/farmacologia , Encéfalo/efeitos dos fármacos , Cães/metabolismo , Isoflurano/farmacologia , Éteres Metílicos/farmacologia , Pregnanodionas/farmacologia , Propofol/farmacologia , Espectroscopia de Prótons por Ressonância Magnética/métodos , Animais , Encéfalo/metabolismo , Química Encefálica/efeitos dos fármacos , Estudos Cross-Over , Feminino , Masculino , Sevoflurano
19.
Biomed Pharmacother ; 102: 153-159, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29554593

RESUMO

Anesthetic preconditioning is a cellular protective approach whereby exposure to a volatile anesthetic renders cardio injury. Sevoflurane preconditioning has been shown to exhibit cardio protective effect on hypoxia/reoxygenation (H/R) injury, but the underlying mechanism is unclear. Syntaxin 1A (STX1A), an important regulator in cardio disease, was predicted to be the target gene of microRNA-34a-5p (miR-34a-5p). The current research was designed to delineate the role of miR-34a-5p in regulating sevoflurane preconditioning in cardiomyocytes injury. In this study, the results demonstrated that the expression of STX1A was significantly increased, while miR-34a-5p was dramatically decreased in sev-preconditioning H9c2 cells as compared with cells only under H/R stimulation. Moreover, miR-34a-5p regulated the protective effect of sev-preconditioning in injured H9c2 cells by mediating cell proliferation and cell apoptosis. Additionally, the luciferase report confirmed the targeting reaction between STX1A and miR-34a-5p. Taken together, our study suggested that miR-34a-5p regulated sev-preconditioning induced inhibition of hypoxia/reoxygenation injury through mediating STX1A, provided a potential therapeutic target for anesthetic protection in cardio disease.


Assuntos
Éteres Metílicos/farmacologia , MicroRNAs/genética , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica , Éteres Metílicos/administração & dosagem , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/patologia , Ratos , Sevoflurano , Sintaxina 1/genética
20.
Immunol Invest ; 47(4): 327-334, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29412077

RESUMO

The effects of anesthetics on immune cell apoptosis and cytokine stimulation were studied in a prospective study. American Society of Anesthesiologists I/II patients underwent elective inguinal hernia repair or varicose veins stripping surgery and were randomized to either epidural anesthesia (n = 14) or general anesthesia with sevoflurane (n = 19) or propofol (n = 15). Blood was sampled before anesthesia induction (T0), at the end of surgery (T1), and 6 h later (T2). Apoptosis was determined by ANNEXIN-V staining of white blood cells; monocytes were isolated and stimulated for cytokine production. Results were compared with 10 healthy volunteers well-matched for age and gender. Apoptosis of lymphocytes and monocytes was increased in the epidural and sevoflurane groups at T2. Propofol group had increased production of interleukin-6 at T1 and sevoflurane and epidural groups had decreased production of tumor necrosis factor-alpha at T2. Results emphasize the modulation of immune function by epidural and sevoflurane but not propofol anesthesia in a clinical setting.


Assuntos
Anestesia Geral , Anestésicos/farmacologia , Apoptose/efeitos dos fármacos , Citocinas/metabolismo , Leucócitos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Adulto , Anestesia Epidural , Feminino , Humanos , Leucócitos/metabolismo , Masculino , Éteres Metílicos/farmacologia , Pessoa de Meia-Idade , Fenótipo , Propofol/farmacologia , Sevoflurano
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