Association between telomere length in the DNA of peripheral blood leukocytes and the propofol dose in anesthesia induction: an observational study

Abstract Introduction: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. Methods: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5'end or 3'end of TERC was detected. We recruited 100 patients of elective surgery. Results: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5' end or 3' end of TERC was not found. Conclusions: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.

Role of melatonin in attenuation of hemodynamic response to intubation and anesthetic requirements: a randomized, controlled, double-blind study

Abstract Background Melatonin has been studied to have anxiolytic, sedative, and analgesic effects. However, there is limited data on the effect of melatonin in the attenuation of hemodynamic response to intubation. We aimed to study whether preanesthetic oral melatonin attenuates hemodynamic responses to intubation and anesthetic requirements. Methods Sixty-four patients scheduled for laparoscopic cholecystectomy were randomized into melatonin or placebo group (n = 32 each). Melatonin group received two tablets (3 mg each) of melatonin, and the placebo group received two tablets of vitamin D3 120 min before induction. Hemodynamic parameters were recorded during induction and postintubation for 15 minutes. Total induction dose of propofol, total intraoperative fentanyl consumption, and adverse effects of melatonin were also noted. Results Postintubation rise in heart rate (HR) was less in the melatonin group compared to the placebo group (10.59% vs. 37.08% at 1 min, respectively) (p< 0.0001). Maximum percentage increase in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) was lesser in melatonin group than placebo group (SBP 9.25% vs. 37.73%, DBP 10.58% vs. 35.51%, MBP 9.99% vs. 36.45% at 1 min postintubation. respectively) (p< 0.0001). Induction dose of propofol (1.42 mg.kg-1 vs. 2.01 mg.kg-1) and the number of patients requiring additional fentanyl intraoperatively (3 vs. 11) were also significantly reduced in the melatonin group. Conclusion Premedication with 6 mg of oral melatonin resulted in significant attenuation of postintubation rise in HR, SBP, DBP, and MBP. It also reduced the induction dose of propofol, total intraoperative fentanyl consumption without any adverse effects.

Activation of GABAergic neurons in the zona incerta accelerates anesthesia induction with sevoflurane and propofol without affecting anesthesia maintenance or awakening in mice / 南方医科大学学报

OBJECTIVE@#To explore the regulatory effects of GABAergic neurons in the zona incerta (ZI) on sevoflurane and propofol anesthesia.@*METHODS@#Forty-eight male C57BL/6J mice divided into 8 groups (n=6) were used in this study. In the study of sevoflurane anesthesia, chemogenetic experiment was performed in 2 groups of mice with injection of either adeno-associated virus carrying hM3Dq (hM3Dq group) or a virus carrying only mCherry (mCherry group). The optogenetic experiment was performed in another two groups of mice injected with an adeno-associated virus carrying ChR2 (ChR2 group) or GFP only (GFP group). The same experiments were also performed in mice for studying propofol anesthesia. Chemogenetics or optogenetics were used to induce the activation of GABAergic neurons in the ZI, and their regulatory effects on anesthesia induction and arousal with sevoflurane and propofol were observed; EEG monitoring was used to observe the changes in sevoflurane anesthesia maintenance after activation of the GABAergic neurons.@*RESULTS@#In sevoflurane anesthesia, the induction time of anesthesia was significantly shorter in hM3Dq group than in mCherry group (P < 0.05), and also shorter in ChR2 group than in GFP group (P < 0.01), but no significant difference was found in the awakening time between the two groups in either chemogenetic or optogenetic tests. Similar results were observed in chemogenetic and optogenetic experiments with propofol (P < 0.05 or 0.01). Photogenetic activation of the GABAergic neurons in the ZI did not cause significant changes in EEG spectrum during sevoflurane anesthesia maintenance.@*CONCLUSION@#Activation of the GABAergic neurons in the ZI promotes anesthesia induction of sevoflurane and propofol but does not affect anesthesia maintenance or awakening.

Roles of c-Fos, EGR-1, PKA, and PKC in cognitive dysfunction in rats after propofol anesthesia

Abstract This study aimed to investigate possible changes in the spatial memory of rats and the expression or activity of EGR-1, c-Fos, PKA, and PKC after propofol anesthesia. Thirty-six Sprague-Dawley rats aged 20 months and 36 Sprague-Dawley rats aged three months were each randomly divided into three groups: the control group, the Morris Water Maze (MWM) group, and the propofol group. In the propofol groups of both young and aged rats, the rats were anesthetized by propofol for two or four hours and then performed the MWM test two days or two weeks after anesthesia to assess cognitive function. EGR-1, c-Fos, PKA, and PKC expressions in the rat hippocampus were determined via immunohistochemistry. For the older rats, the escape latency in the P4h/2d group was significantly prolonged (P < 0.05), and the learning curve was right-shifted in the P4h/2w group (P < 0.05). The expression levels of EGR-1, c-Fos, PKA, and PKC in the MWM groups were significantly higher than those in the control groups (P < 0.05). In the P4h/2d group of aged rats, the expression levels of both PKA and PKC were decreased compared with those of the MWM groups. The decreased expression of both protein kinases may be responsible for the observed impairment after propofol anesthesia

Effects of propofol on inflammatory response and activation of p38 MAPK signaling pathway in rats with ventilator-induced lung injury

ABSTRACT Purpose: To investigate the effects of propofol on inflammatory response and activation of p38 mitogen-activated protein kinase (MAPK) signaling pathway in rats with ventilator-associated lung injury (VALI). Methods: Thirty-six Sprague Dawley (SD) rats were divided into control, VALI and VALI+propofol groups. The VALI group received the mechanical ventilation for 2 h. The VALI+propofol group received the mechanical ventilation for 2 h, which was accompanied by intravenous injection of propofol with dose of 8 mg·kg-1·h-1. At the end, the mean arterial pressure (MAP) and blood gas indexes were measured, and the lung wet/dry mass ratio (W/D) and biochemical indexes of lung tissue and bronchoalveolar lavage fluid (BALF) were determined. Results: Compared with VALI group, in VALI+propofol group the blood pH, partial pressure of oxygen, partial pressure of carbon dioxide and MAP were increased, the lung W/D, lung tissue myeloperoxidase activity and total protein concentration, white blood cell count, and tumor necrosis factor α, interleukin 1β and interleukin 6 levels in BALF were decreased, and the p-p38 MAPK protein expression level and phosphorylated p38 MAPK (p-p38 MAPK)/p38 MAPK ratio were decreased. Conclusions: Propofol treatment may alleviate the VALI in rats by reducing the inflammatory response and inhibiting the activation of p38 MAPK signaling pathway.

Mechanisms for propofol in inhibiting the proliferation and invasion of glioma U87 cells and its effect on miR-134 expression / 中南大学学报(医学版)

OBJECTIVES@#To investigate the effects of propofol on the proliferation and invasion of glioma U87 cells and to explore the possible anti-tumor mechanisms.@*METHODS@#The glioma U87 cells was divided into a blank group, a positive control group, and the propofol groups (1.00, 2.00 or 5.00 mmol/L). Cell counting kit-8 (CCK-8) was used to detect cell proliferation; Transwell method was used to detect the effect of propofol on invasion and migration of U87 cells; real-time PCR was used to detect the expression of microRNA-134 (miR-134); Western blotting was used to detect the expression levels of reproduction-related protein Ki-67, invasion-related protein metalloproteinase-2 (MMP-2), metalloproteinase-9 (MMP-9) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway-related protein.@*RESULTS@#Compared with the blank group, the proliferation, invasion and migration capacity of U87 cells were reduced in the positive control group and the propofol groups after 48 hours (all @*CONCLUSIONS@#Propofol can decrease the proliferation rate, and the invasion and migration abilities of U87 cells, which may be achieved by up-regulation of miR-134 and suppression of PI3K/Akt signaling pathway.

The myocardial protective effect of propofol on rats with experimental myocardial infarction and its mechanism / 生理学报

The aim of the present study was to investigate the protective effect of propofol on the experimental myocardial infarction in rats. The myocardial infarction model was established by ligating the anterior descending branch of left coronary artery in rats. Model rats were treated with propofol. Cardiac function was evaluated by echocardiography. Cardiac hemodynamic changes were detected by multiconductor biorecorder. Pathological changes in the infarcted myocardia were detected by HE staining. The expression levels of cardiac hypertrophy marker genes and fibrosis marker proteins were analyzed by real-time quantitative PCR and Western blot. The results showed that, compared with the sham surgery group, the model group exhibited larger infarct size (> 40%), impaired heart function, and significantly increased left ventricular end-diastolic pressure (LVEDP). Propofol reduced cardiac function impairment and decreased LVEDP in the model group. Propofol significantly reduced lung weight/body weight ratio, heart weight/body weight ratio, left ventricular weight/body weight ratio and left atrial weight/body weight ratio in the model group. Furthermore, after myocardial infarction, the administration of propofol significantly improved the diastolic strain rate, down-regulated the mRNA expression levels of myocardial hypertrophy markers, atrial natriuretic peptide and β-myosin heavy chain, and reversed the up-regulation of matrix metalloproteinase 2 (MMP2), MMP9 and tissue inhibitor of metalloproteinase-2 (TIMP-2) induced by myocardial infarction. These results suggest propofol can reduce adverse ventricular remodeling, cardiac dysfunction, myocardial hypertrophy and fibrosis after myocardial infarction, and has protective effect against the experimental myocardial infarction induced by coronary artery ligation in rats.

Propofol use in newborns and children: is it safe? A systematic review / Utilização do propofol em recém-nascidos e crianças: é segura? Uma revisão sistemática

Abstract Objectives: To determine the main indications and assess the most common adverse events with the administration of hypnotic propofol in most pediatric clinical scenarios. Sources: A systematic review of PubMed, SciELO, Cochrane, and EMBASE was performed, using filters such as a maximum of five years post-publication, and/or references or articles of importance, with emphasis on clinical trials using propofol. All articles of major relevance were blind-reviewed by both authors according to the PRISMA statement, looking for possible bias and limitations or the quality of the articles. Summary of the findings: Through the search criterion applied, 417 articles were found, and their abstracts evaluated. A total of 69 papers were thoroughly studied. Articles about propofol use in children are increasing, including in neonates, with the majority being cohort studies and clinical trials in two main scenarios: upper digestive endoscopy and magnetic resonance imaging. A huge list of adverse events has been published, but most articles considered them of low risk. Conclusions: Propofol is a hypnotic drug with a safe profile of efficacy and adverse events. Indeed, when administered by non-anesthesiologists, quick access to emergency care must be provided, especially in airway events. The use of propofol in other scenarios must be better studied, aiming to reduce the limitations of its administration by general pediatricians.

Resumo Objetivos: Determinar as principais indicações e examinar os eventos adversos mais comuns com uso do hipnótico propofol na maioria dos cenários clínicos pediátricos. Fontes: Realizada revisão sistemática da literatura nas bases de dados PubMed, Scielo, Cochrane e EMBASE, aplicando-se filtros como máximo de cinco anos de publicação e/ou referências ou publicações relevantes em outras hipóteses com enfoque em ensaios clínicos envolvendo o propofol. Todos os artigos de maior relevância foram avaliados cegamente pelos dois autores, de acordo com o PRISMA Statement, observando os riscos de vieses e qualidades ou limitações dos estudos. Resumo dos achados: Através dos mecanismos de pesquisa, 417 artigos foram encontrados e separados logo após, de acordo com os critérios de inclusão. Um total de 69 artigos foram estudados. Destacam-se a produção científica crescente sobre o propofol em crianças, incluindo recém-nascidos, sendo a grande maioria dos trabalhos coortes retrospectivos ou prospectivos, bem como ensaios clínicos com o propofol nos principais cenários: endoscopia digestiva alta e ressonância magnética. Ampla gama de eventos adversos foi citada, mas a maioria dos trabalhos não as consideraram significativas. Conclusões: O propofol apresenta um seguro perfil de eficácia e segurança. Quando administrado por médicos não anestesistas, deve-se redobrar o cuidado para ação rápida em emergências, especialmente de vias aéreas. A aplicação do fármaco em outros contextos deve ser estudada em maior profundidade, a fim de dirimir a dificuldade do uso por pediatras.

¿Por qué el propofol en el paciente con cáncer? / ¿Why propofol in the cancer patient?

INTRODUCTION: Cancer is a chronic, incapacitating and high mortality disease. OBJECTIVE: To carry out an update on the beneficial properties of the use of propofol as an anesthetic agent in cancer patients. METHODOLOGICAL DESIGN: A manual and digital search was performed in different databases such as MEDLINE, Scielo, IBECS and Cochrane, with the following descriptors: propofol, cancer, immunity and cancer. Development: 90% of deaths related to cancer are due to the progression of the disease, to metastases and not to the primary tumor. Therefore, preventing immunosuppression in the perioperative period is particularly important. During the perioperative period, there are factors that activate or inhibit immune responses. Recent findings have suggested that anesthesia can induce metabolic, inflammatory and immunological changes in the perioperative period. Propofol promotes the cytotoxicity of natural killer cells, reduces the motility of tumor cells, inhibits cyclo-oxygenase. It has been revealed that this drug exhibits anticancer properties in some types of cancer: colon cancer, gastric cancer, bile duct cancer. CONCLUSIONS: Propofol has a potential benefit as an anesthetic agent in patient with cancer. Only the accumulation of even more scientific evidence would allow us to give greater value to the use of this drug.

INTRODUCCIÓN: El cáncer es una enfermedad crónica, incapacitante y de gran mortalidad. OBJETIVO: Realizar una actualización sobre las beneficiosas propiedades del uso del propofol como agente anestésico en el paciente oncológico. DISEÑO METODOLÓGICO: Se realizó una búsqueda manual y digital en diferentes bases de datos como MEDLINE, Scielo, IBECS y Cochrane, con los descriptores siguientes: propofol, cáncer, inmunidad y cáncer. Desarrollo: El 90% de las muertes relacionadas con el cáncer son debido a la progresión de la enfermedad, a las metástasis y no al tumor primario. Por ello, prevenir la inmunosupresión en el período perioperatorio toma particular importancia. Durante el periodo perioperatorio existen factores que activan o inhiben las respuestas inmunitarias. Los descubrimientos recientes han sugerido que la anestesia puede inducir cambios metabólicos, inflamatorios e inmunológicos en el período perioperatorio. El propofol favorece la citotoxicidad de las células naturalkiller, reduce la motilidad de las células tumorales, inhibe la ciclooxigenasa. Ha sido revelado que este fármaco exhibe propiedades anticancerosas en algunos tipos de cáncer: cáncer de colon, cáncer gástrico, cáncer de vías biliares. CONCLUSIONES: El propofol presenta un potencial beneficio como agente anestésico en el paciente con cáncer. Solo bastaría la acumulación de aún más evidencia científica que nos permita darle mayor valor al uso de este fármaco.

The role of PI3K/Akt signal pathway in the protective effects of propofol on intestinal and lung injury induced by intestinal ischemia/reperfusion

Abstract Purpose: To investigate the role of PI3k/Akt signal pathway in the protective effects of propofol on intestinal and lung injury induced by intestinal ischemia/reperfusion(I/R). Methods: Male Sprague-Dawley rats were subjected to 45 min of ischemia by occluding the superior mesenteric artery and to 2h of reperfusion to establish the model of I/R. Twenty four rats were randomly divided into four groups: Sham, intestinal I/R (II/R), propofol (P), wortmannin (W). In groups P, W, propofol was injected intravenously and continuously at the onset of reperfusion via infusion pump. PI3K inhibitor (wortmannin) was administered intravenously in group W 25 min before ischemia. Intestinal tissues and lung tissues were obtained for determination of histologic injury, wet/dry weight ratio, malondialdehyde (MDA) levels, superoxide dismutase (SOD) and myeloperoxidase (MPO) activities. Meanwhile, the expressions of caspase-3 and phosphorylated Akt (p-Akt) in intestines and lungs were detected by western blot. Results: Propofol treatment alleviated intestinal and lung morphological changes which were observed in II/R group，Moreover, wet/dry weight ratio, the MDA level, MPO activity and expression of caspase-3 were significantly decreased whereas the SOD activity and p-Akt expression were significantly increased. Notably, the protections were significantly reversed by pretreatment of wortmannin. Conclusion: PI3K/Akt pathway activation play a critical role in the protective effects of propofol on intestinal and lung injury induced by ischemia/reperfusion.

Propofol, fentanyl and remifentanil do not impair the phagocytic capacity to of human peripheral blood polimorphonuclear cells / Propofol, fentanil y remifentanil no alteran la capacidad de las células polimorfonucleares humanas de fagocitar a la Candida albicans

OBJECTIVES: The capacity of polymorphonuclear cells (PMN) to phagocyte microorganisms is an important function to be preserved during surgical interventions. Therefore, the aim of this study was to determine the effect of propofol, fentanyl and remifentanil combination on Candida albicans engulfment by human PMN. MATERIALS AND METHODS: Twenty patients scheduled to undergo surgical interventions (ASA I-II) received propofol, fentanyl and remifentanil as intravenous anesthesia. PMNs were obtained before and after the surgical procedure and phagocytosis assay was performed using opsonized C. albicans. RESULTS AND CONCLUSIONS: No differences between the values obtained before and after anesthesia treatment in the number of phagocytic PMN and the number of C. albicans engulfed were observed. These results suggest that the used anesthesic protocol does not alter one of the most important immune mechanisms.

OBJETIVOS: La capacidad de las células polimorfonucleares (CPN) de fagocitar a los microorganismos es una importante función que se debe de preservar durante las intervenciones quirúrgicas. Por lo tanto, el propósito de este estudio fue determinar el efecto de la combinación del propofol, el fentanil y el remifentanil en la ingestión de Candida albicans por parte de las CPN humanas. MATERIALES Y MÉTODOS: Veinte pacientes sujetos a intervenciones quirúrgicas (ASA I-II) recibieron propofol, fentanil y remifentanil como anestesia endovenosa. Los CPN se obtuvieron antes y después del procedimiento quirúrgico y el ensayo de fagocitosis fue realizando usando C. albicans opsonizada. RESULTADOS Y CONCLUSIONES: No se observaron diferencias significativas en los valores obtenidos antes y después del tratamiento anestésico tanto en el número de CPN fagocíticas como en el número de C. albicans dentro de las células. Estos hallazgos sugieren que el protocolo anestésico usado no altera uno de los mecanismos de defensa más importante del organismo.

Effects of propofol pretreatment on myocardial cell apoptosis and SERCA2 expression in rats with hepatic ischemia/reperfusion / Efeitos do pré-tratamento com propofol sobre a apoptose de células miocárdicas e expressão de SERCA2 em ratos com isquemia/reperfusão hepática

Abstract Introduction: Hepatic ischemia-reperfusion injury is a common pathophysiological process in liver surgery. Whether Propofol can reduce myocardial ischemia-reperfusion injury induced by hepatic ischemia-reperfusion injury in rats, together with related mechanisms, still needs further studies. Objective: To investigate if propofol would protect the myocardial cells from apoptosis with hepatic ischemia-reperfusion injury. Methods: Male Sprague-Dawley rats (n = 18) were randomly allocated into three groups: Sham Group (Group S, n = 6), Hepatic Ischemia-reperfusion Injury Group (Group IR, n = 6) and Propofol Group (Group P, n = 6). Group S was only subjected to laparotomy. Group IR was attained by ischemia for 30 min and reperfusion for 4 h. Group P was subjected identical insult as in Group IR with the administration of propofol started 10 min before ischemia with 120 mg.kg−1, following by continuous infusion at 20 mg.kg−1.h−1. Cell apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. Endoplasmic reticulum Ca2+-ATPase2 (SERCA2) and cysteine-containing aspartic acid cleaved-caspase3 (cleaved-caspase3) were assayed by western blot and Altimeter polymerase chain reaction. Results: Apoptosis rate was increased, with mRNA and protein of SERCA2 down-regulated and cleaved-caspase3 up-regulated in Group IR compared with Group S (p < 0.01). Apoptosis rate was decreased, with mRNA and protein of SERCA2 up-regulated and cleaved-caspase3 down-regulated in Group P compared with Group IR (p < 0.01). Conclusions: Propofol can reduce hepatic ischemia-reperfusion injury-induced myocardial cell apoptosis, meanwhile, can up-regulate mRNA and protein of SERCA2 in rats.

Resumo Introdução: A lesão hepática por isquemia-reperfusão é um processo fisiopatológico comum em cirurgias hepáticas. Mais estudos ainda são necessários para avaliar se o propofol pode reduzir a lesão de isquemia-reperfusão miocárdica induzida pela lesão de isquemia-reperfusão hepática em ratos, juntamente com os mecanismos que estão relacionados. Objetivo: Investigar se propofol protege as células do miocárdio da apoptose com a lesão hepática por isquemia-reperfusão. Métodos: Ratos machos da raça Sprague-Dawley (n = 18) foram alocados aleatoriamente em três grupos: Grupo Sham (Grupo S, n = 6), Grupo Lesão Hepática por Isquemia-reperfusão (Grupo IR, n = 6) e Grupo Propofol (Grupo P, n = 6). O Grupo S foi submetido apenas à laparotomia. O grupo IR foi submetido à isquemia por 30 min e reperfusão por 4 h. O grupo P foi submetido à mesma isquemia do grupo IR, com a administração de 120 mg.kg-1 de propofol iniciada 10min antes da isquemia, seguida de infusão contínua a 20 mg.kg-1.h-1. A apoptose celular foi examinada por meio do ensaio de marcação de terminações dUTP pela deoxinucleotidil transferase. Retículo endoplasmático Ca2+-ATPase2 (SERCA2) e caspase-3 do ácido aspártico contendo cisteína (caspase-3 clivada) foram avaliados com o ensaio western blot e reação em cadeia da polimerase. Resultados: A taxa de apoptose foi maior com mRNA e proteína de SERCA2 regulados para baixo e caspase-3 clivada suprarregulada no Grupo IR, em comparação com o Grupo S (p < 0,01). A taxa de apoptose foi menor com mRNA e proteína de SERCA2 suprarregulada e caspase-3 clivada sub-regulada no Grupo P, em comparação com o Grupo IR (p < 0,01). Conclusões: O propofol pode reduzir a apoptose de células miocárdicas induzida por lesão hepática por isquemia-reperfusão. Entretanto, pode suprarregular o mRNA e a proteína de SERCA2 em ratos.

Effects of propofol pretreatment on lung morphology and heme oxygenase-1 expression in oleic acid-induced acute lung injury in rats

Abstract Purpose: To investigate the effects of propofol pretreatment on lung morphology and heme oxygenase-1 expression in oleic acid -induced acute lung injury in rats. Methods: A total of 32 male Sprague-Dawley rats (250-300g) were randomly divided into the following four groups (n=8/group): group C, group OA, group OA+PR, and group OA+IX to compare related parameter changes. Results: PaO2, PCO2, and PaO2/FiO2 were significantly different among the four treatment groups (P<0.05 or P<0.01). Lung wet/dry weight ratio and HO-1 protein expression also significantly differed among the groups (P<0.01). Immunohistochemistry showed that the expression of HO-1 in group OA+PR was stronger than those in groups OA, OA+IX, and C. Light microscopy revealed that pathological changes in lung tissues in group OA+PR were milder than those in group OA and group OA+IX. Electron microscopy showed that alveolar type II epithelial cell ultrastructure in group OA was relatively irregular with cell degeneration and disintegration and cytoplasmic lamellar bodies were vacuolized. Changes in group OA+PR were milder than those in group OA; however, they were more severe in group OA+IX than in group OA. Conclusion: Propofol significantly increases the expression of HO-1 in the lung tissueand prevents changes in lung morphology due to ALI in rats.

The antimicrobial activity of ephedrine and admixture of ephedrine and propofol: an in vitro study / A atividade antimicrobiana de efedrina e da combinação de efedrina e propofol: um estudo in vitro

Abstract Introduction Propofol and Ephedrine are commonly used during anesthesia maintenance, the former as a hypnotic agent and the later as a vasopressor. The addition of propofol to ephedrine or administration of ephedrine before propofol injection is useful for decreasing or preventing propofol related hemodynamic changes and vascular pain. This in vitro study evaluated the antibacterial effect on common hospital-acquired infection pathogens of ephedrine alone or combined with propofol. Material and method The study was performed in two stages. In the first, the Minimum Inhibitory Concentration of propofol and ephedrine alone and combined was calculated for Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Pseudomonas aeruginosa, and a clinical isolate of Acinetobacter spp. at 0, 6, 12 and 24 h, using the microdilution method. In the second stage, the same drugs and combination were used to determine their effect on bacterial growth. Bacterial solutions were prepared at 0.5 MacFarland in sterile 0.9% physiological saline and diluted at 1/100 concentration. Colony numbers were measured as colony forming units.mL-1 at 0, 2, 4, 6, 8, 10 and 12th hours. Results Ephedrine either alone or combined with propofol did not have an antimicrobial effect on Escherichia coli, Enterococcus faecium, or Pseudomonas aeruginosa and this was similar to propofol. However, ephedrine alone and combined with propofol was found to have an antimicrobial effect on Staphylococcus aureus and Acinetobacter species at 512 mcg.mL-1 concentration and significantly decreased bacterial growth rate. Conclusion Ephedrine has an antimicrobial activity on Staphylococcus aureus and Acinetobacter species which were frequently encountered pathogens as a cause of nosocomial infections.

Resumo Introdução Propofol e efedrina são fármacos comumente usados durante a manutenção da anestesia, o primeiro como agente hipnótico e o segundo como vasopressor. A adição de propofol à efedrina ou a administração de efedrina antes da injeção de propofol é útil para diminuir ou prevenir alterações hemodinâmicas e dor vascular relacionadas ao propofol. Este estudo in vitro avaliou o efeito antibacteriano de efedrina, isolada ou em combinação com propofol, em patógenos comuns implicados em infecção hospitalar. Material e método O estudo foi feito em duas etapas. Na primeira, a concentração inibitória mínima (CIM) de propofol e de efedrina isolada e em combinação foi calculada para Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Pseudomonas aeruginosa e um isolado clínico de Acinetobacter spp às 0, 6, 12 e 24 horas, com o método de microdiluição. Na segunda etapa, o mesmo fármaco e sua combinação foram usados para determinar seus efeitos no crescimento bacteriano. As soluções bacterianas foram preparadas em soro fisiológico a 0,9% em 0,5 McFarland e diluídas a uma concentração de 1/100. Os números das colônias foram medidos como ufc.mL-1 às 0, 2, 4, 6, 8, 10 e 12 horas. Resultados Efedrina isolada ou em combinação com propofol não apresentou efeito antimicrobiano sobre E. coli, E. faecium ou P. aeruginosa, um resultado semelhante ao de propofol. Porém, efedrina isolada e em combinação com propofol apresentou efeito antimicrobiano sobre Staphylococcus aureus e Acinetobacter spp, em concentração de 512 mcg.mL-1, e redução significativa da taxa de crescimento bacteriano. Conclusão Efedrina tem atividade antimicrobiana em S. aureus e Acinetobacter spp, patógenos frequentemente identificados como causa de infecções nosocomiais.

Propofol inhibits proliferation, migration, and invasion but promotes apoptosis by regulation of Sox4 in endometrial cancer cells

Propofol is an intravenous sedative hypnotic agent of which the growth-inhibitory effect has been reported on various cancers. However, the roles of propofol in endometrial cancer (EC) remain unclear. This study aimed to explore the effects of propofol on EC in vitro and in vivo. Different concentrations of propofol were used to treat Ishikawa cells. Colony number, cell viability, cell cycle, apoptosis, migration, and invasion were analyzed by colony formation, MTT, flow cytometry, and Transwell assays. In addition, the pcDNA3.1-Sox4 and Sox4 siRNA plasmids were transfected into Ishikawa cells to explore the relationship between propofol and Sox4 in EC cell proliferation. Tumor weight in vivo was measured by xenograft tumor model assay. Protein levels of cell cycle-related factors, apoptosis-related factors, matrix metalloproteinases 9 (MMP9), matrix metalloproteinases 2 (MMP2) and Wnt/β-catenin pathway were examined by western blot. Results showed that propofol significantly decreased colony numbers, inhibited cell viability, migration, and invasion but promoted apoptosis in a dose-dependent manner in Ishikawa cells. Moreover, propofol reduced the expression of Sox4 in a dose-dependent manner. Additionally, propofol significantly suppressed the proportions of Ki67+ cells, but Sox4 overexpression reversed the results. Furthermore, in vivo assay results showed that propofol inhibited tumor growth; however, the inhibitory effect was abolished by Sox4 overexpression. Moreover, propofol inhibited Sox4 expression via inactivation of Wnt/β-catenin signal pathway. Our study demonstrated that propofol inhibited cell proliferation, migration, and invasion but promoted apoptosis by regulation of Sox4 in EC cells. These findings might indicate a novel treatment strategy for EC.

Propofol attenuates sepsis-induced acute kidney injury by regulating miR-290-5p/CCL-2 signaling pathway

Previous studies have indicated that propofol has immunomodulatory and antioxidative properties. However, the renoprotection effect and the precise mechanisms of propofol in sepsis-induced renal injury remain unclear. The purpose of the present study was to investigate the role of miR-290-5p/CCL-2 signaling in septic mice treatment with propofol. Mice were treated with propofol (50 mg/kg) twice within 24 h. Survival outcome was monitored within 48 h. The mRNA and protein levels were assayed by qRT-PCR and western blotting, respectively. Mouse podocytes (MPC5) were treated with lipopolysaccharide (LPS) to establish the cell model in vitro. The proliferation of MPC5 was monitored using the MTS assay. Cell apoptosis was analyzed by flow cytometry. Propofol improved survival outcome and alleviated acute kidney injury in cecal ligation and puncture-operated mice. Propofol increased miR-290-5p expression and decreased CCL-2 and inflammatory cytokines levels in the kidney for septic mice. We found that miR-290-5p was a direct regulator of CCL-2 in MPC5. Propofol could abrogate LPS-induced growth inhibition and apoptosis in MPC5. Meanwhile, propofol inhibited CCL-2 expression in LPS-treated MPC5, however, knockdown of miR-290-5p abrogated the inhibitory effect propofol on the mRNA and protein expressions of CCL-2. Propofol could serve as an effective therapeutic medication to suppress sepsis-induced renal injury in vivo and in vitro by regulating the miR-290-5p/CCL-2 signaling pathway.

Impact of propofol on renal ischemia/reperfusion endoplasmic reticulum stress

Abstract Purpose: To investigate the protective mechanisms of propofol (Pro) on renal ischemia/reperfusion (I/R) injury by studying its impact on renal I/R endoplasmic reticulum stress. Methods: Eighteen male Sprague-Dawley rats (SD rats) were randomly divided into three groups: the I/R group, the Pro pretreatment group, and the control group, and corresponding treatments were performed. The levels of serum creatinine (Cr) and blood urea nitrogen (BUN) of each group were detected. The expression levels of CCAAT-enhancer-binding protein (C/EBP) homology protein (CHOP) and caspase-12 protein within renal tissue samples were detected by western blot. Results: The periodic acid-Schiff (PAS) staining was performed to observe the morphological changes within the renal tissues, and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay was performed to detect the presence of renal apoptosis. The Pro pretreatment significantly reduced the serum Cr and BUN levels, as well as the expressions levels of CHOP and caspase-12 protein inside the kidney of I/R rats, improving renal pathological injury and reducing the I/R-induced renal apoptosis. Conclusion: Propofol could downregulate the expression of stress-apoptotic proteins CHOP and caspase-12 in the endoplasmic reticulum, thus reducing renal I/R injury.

Propofol attenuates cytokine-mediated upregulation of expression of inducible nitric oxide synthase and apoptosis during regeneration post-partial hepatectomy

Abstract Purpose: To determine the effects of propofol and ketamine anesthesia on liver regeneration in rats after partial hepatectomy (PHT). Methods: Male Wistar albino rats were assigned randomly to four groups of 10. Anesthesia was induced and maintained with propofol in groups 1 and 2, and with ketamine in groups 3 and 4. PHT was undertaken in groups 1 and 3. Rats in groups 2 and 4 (control groups) underwent an identical surgical procedure, but without PHT. At postoperative day-5, rats were killed. Regenerated liver was removed, weighed, and evaluated (by immunohistochemical means) for expression of inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS), apoptosis protease-activating factor (APAF)-1, and proliferating cell nuclear antigen (PCNA). Also, blood samples were collected for measurement of levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6. Results: Between groups 2 and 4, there were no differences in tissue levels of iNOS, eNOS, and APAF-1 or plasma levels of TNF-α and IL-6. eNOS expression was similar in group 1 and group 3. Expression of iNOS and APAF-1 was mild-to-moderate in group 1, but significantly higher in group 3. Groups 1 and 3 showed an increase in PCNA expression, but expression in both groups was comparable. Plasma levels of TNF-α and IL-6 increased to a lesser degree in group 1 than in group 3. Conclusion: Propofol, as an anesthetic agent, may attenuate cytokine-mediated upregulation of iNOS expression and apoptosis in an animal model of liver regeneration after partial hepatectomy.

Cyclosporine A attenuates apoptosis and necrosis after ischemia-reperfusion-induced renal injury in transiently hyperglycemic rats

Abstract Purpose: To investigate the effects of cyclosporine A on renal ischemia-reperfusion injury during transient hyperglycemia in rats. Methods: In a model of ischemia-reperfusion-induced renal injury and transiently induced hyperglycemia by intraperitoneal injection of glucose, 2.5 g.kg-1, Wistar rats were anesthetized with either isoflurane or propofol and received intravenous cyclosporine A, 5 mg.kg-1, five minutes before reperfusion. Comparison groups were isoflurane and propofol sham groups and isoflurane and propofol ischemia-reperfusion-induced renal injury. Renal tubular cell viability was quantitatively assessed by flow cytometry after cell culture and classified as early apoptosis, necrotic cells, and intact cells. Results: Early apoptosis was significantly higher in isoflurane and propofol anesthetized animals subjected to renal ischemia-reperfusion injury when compared to both cyclosporine A treated and sham groups. Necrosis percentage was significantly higher in propofol-anesthetized animals subjected to renal ischemia-reperfusion injury. The percentage of intact cells was lower in both, isoflurane and propofol anesthetized animals subjected to renal ischemia-reperfusion injury. Conclusion: In a model of ischemia-reperfusion-induced renal injury, cyclosporine A, 5 m.kg-1, administered five minutes before renal reperfusion in rats with acute-induced hyperglycemia under either isoflurano or propofol anesthesia, attenuated early apoptosis and preserved viability in renal tubular cells, regardless of the anesthetic used.

Comparisons of the effects of the sevoflurane and propofol on acute ischemia reperfusion and DNA damages in rabbits / Comparações dos efeitos de sevoflurano e propofol sobre isquemia-reperfusão aguda e danos ao DNA em coelhos

Abstract Background and objectives: The aim of this study was to compare the effects of sevoflurane and propofol anesthesia on oxidative DNA damage that occurs in low-extremity ischemia and is caused by tourniquet application. Methods: Fourteen New Zealand rabbits were randomly allocated into two equal groups. Group S (n = 7) received sevoflurane (2.5-4 percent) inhalation and Group P (n = 7) received a propofol infusion (1-2 mg·kg-1·min-1), after which a pneumatic tourniquet was placed on the right lower extremity. Blood samples were collected prior to tourniquet placement (baseline), 120 min after ischemia, 15 min after ischemia and 120 minutes (min) after ischemia. Malondialdehyde (MDA) levels were analyzed to determine lipid peroxidation, and single cell gel electrophoresis (SCGE) was used to determine DNA damage. Results: At 15 min after ischemia, the MDA levels in Group P (8.15 ± 2.61 µM) were higher than baseline (6.26 ± 3.19 µM, p = 0.026) and Group S (4.98 ± 0.77 µM, p = 0.01). DNA damage was similar in both groups, although DNA damage was higher than baseline (tail moment 0.63 ± 0.27, tail intensity 3.76 ± 1.26) in Group P at the 15th minute of reperfusion (tail moment 1.05 ± 0.45, p = 0.06; tail intensity 5.33 ± 1.56, p = 0.01). The increase in tail moment and tail intensity returned to normal levels in both groups 2 hours after the termination of ischemia. Conclusion: Given that oxidative stress and genotoxic effect disappear in the late stages of reperfusion, we conclude that neither sevoflurane nor propofol can be considered superior to the other in anesthesia practices for extremity surgeries involving the use of a tourniquet.

Resumo Justificativa e objetivos: Comparar os efeitos da anestesia com sevoflurano e propofol sobre o dano oxidativo ao DNA que ocorre na isquemia de extremidade inferior e é causada pela aplicação de torniquete. Métodos: Foram alocados aleatoriamente em dois grupos iguais 14 coelhos da raça Nova Zelândia. Grupo S (n = 7) recebeu inalação de sevoflurano (2,5-4%) e Grupo P (n = 7) recebeu perfusão de propofol (1-2 mg·kg-1·min-1), logo após um torniquete pneumático foi colocado na extremidade inferior direita. Amostras de sangue foram coletadas antes da colocação do torniquete (fase basal), após 120 minutos de isquemia, 15 minutos após a isquemia e 120 minutos após a isquemia. Os níveis de malondialdeído (MDA) foram analisados para determinar a peroxidação de lipídios e eletroforese em gel de célula única (EGCU) foi usada para determinar o dano ao DNA. Resultados: Aos 15 minutos após a isquemia, os níveis de MDA no Grupo P (8,15 ± 2,61 µM) foram superiores aos da fase basal (6,26 ± 3,19 µM, p = 0,026) e dp Grupo S (4,98 ± 0,77 µM, p = 0,01). O dano causado ao DNA foi semelhante nos dois grupos, embora tenha sido maior do que na fase basal (momento da cauda 0,63 ± 0,27, intensidade da cauda 3,76 ± 1,26) no Grupo P no 15 minutos de reperfusão (momento da cauda 1,05 ± 0,45, p = 0,06; intensidade da cauda 5,33 ± 1,56, p = 0,01). O aumento no momento da cauda e a intensidade da cauda voltaram aos níveis normais nos dois grupos duas horas após o término da isquemia. Conclusão: Como o estresse oxidativo e o efeito genotóxico desaparecem nos estágios finais da reperfusão, concluímos que não há superioridade tanto de sevoflurano quanto de propofol em práticas de anestesia para procedimentos cirúrgicos de extremidades que envolvem o uso de torniquete.