Influence of endogenous and synthetic female sex hormones on human blood cells in vitro studied with comet assay

The comet assay has been conducted with numerous cell lines to assess in vitro genotoxicity. In order to use the comet assay as part of an in vitro test for evaluating genotoxicity, however, there are cell-specific factors that need to be better understood. In this present study we have evaluated some factors that may impact upon the DNA damage detected in whole blood (WB) cells and lymphocytes (ILs). Experiments were conducted comparing responses of both cells, and investigating the effects of the female hormonal cycle, and oral contraceptive (OC) use on DNA damage detection in the in vitro comet assay, at three sampling time. No significant differences were detected in the basal levels of DNA damage detected in ILs and WB cells from women OC users and non-users and from men. Basal DNA damage in ILs was unaffected by gender and stage of the menstrual cycle or the stage of the treatment schedule. Our results also indicated that the H2O2 induces DNA damage in human lymphocytes independently of gender, low-dose OC use and hormonal fluctuation. However, data showed that in 3rd sampling of menstrual cycle, lymphocytes were more resistant to H2O2-induced DNA damage than those from OC users and men. © 2007 Elsevier Ltd. All rights reserved

Evaluation of DNA damage and lipoperoxidation of propofol in patients undergoing elective surgery

Inhaled anaesthetics have been studied regarding their genotoxic and mutagenic potential in vivo. Propofol differs from volatile anaesthetics because it does not show mutagenic effects and it has been reported to be an antioxidant. However, there are no studies with propofol and genotoxicity in vivo. The study aimed to evaluate the hypothesis that propofol is not genotoxic and it inhibits lipid peroxidation [malondialdehyde (MDA)] in patients undergoing propofol anaesthesia. ASA physical status I patients scheduled for elective surgery, lasting at least 90 min, were enrolled in this study. Initially, the estimated plasma concentration of propofol was targeted at 4 microg ml(-1) and then maintained at 2-4 microg ml(-1) until the end of surgery. Haemodynamic data were determined at baseline (before premedication) and in conjunction with target-controlled infusion of propofol: after tracheal intubation, 30, 60 and 90 min after anaesthesia induction and at the end of the surgery. Venous blood samples were collected at baseline, after tracheal intubation, at the end of the surgery and on the postoperative first day for evaluating DNA damage in white blood cells (WBCs), by comet assay, and MDA levels. Haemodynamic data did not differ among times. No statistically significant differences were observed for the levels of DNA damage in WBCs, nor in plasma MDA, among the four times. Propofol does not induce DNA damage in WBCs and does not alter MDA in plasma of patients

Does occupational exposure to anesthetic gases lead to increase of pro-inflammatory cytokines?

There is great concern about the possible harmful effects of exposure to volatile anesthetics. The current study aimed at evaluating, for the first time, the effects of occupational exposure to anesthetic gases on physicians who work in operating rooms, by determining several inflammatory cytokines. Plasma inflammatory cytokines (IL-1β, -6, -8, -10, -12, TNF-α) were investigated in 30 individuals who were allocated into two groups of 15: the exposed group, consisting of operating room medical personnel exposed to a mixture of anesthetic gases for 3 years, and a control group composed of medical personnel not exposed to anesthetic gases. The concentrations of volatile anesthetics were measured in the operating room by means of an infrared portable analyzer Our findings suggest an increase of the pro-inflammatory IL-8 (p < 0.05) in medical personnel exposed to high concentrations of anesthetic gases, even for a relatively short period

Comparison of waste anesthetic gases in operating rooms with or without an scavenging system in a Brazilian University Hospital

Background and objectives: Occupational exposure to waste anesthetic gases in operating room without active scavenging system has been associated with adverse health effects. Thus, this study aimed to compare the trace concentrations of the inhalational anesthetics isoflurane and sevoflurane in operating room with and without central scavenging system. Method: Waste concentrations of isoflurane and sevoflurane were measured by infrared analyzer at different locations (near the respiratory area of the assistant nurse and anesthesiologist and near the anesthesia station) and at two times (30 and 120 min after the start of surgery) in both operating room types. Results: All isoflurane and sevoflurane concentrations in unscavenged operating room were higher than the US recommended limit (2 parts per million), regardless of the location and time evaluated. In scavenged operating room, the average concentrations of isoflurane were within the limit of exposure, except for the measurements near the anesthesia station, regardless of the measurement times. For sevoflurane, concentrations exceeded the limit value at all measurement locations and at both times. Conclusions: The exposure to both anesthetics exceeded the international limit in unscavenged operating room. In scavenged operating room, the concentrations of sevoflurane, and to a lesser extent those of isoflurane, exceeded the recommended limit value. Thus, the operating room scavenging system analyzed in the present study decreased the anesthetic concentrations, although not to the internationally recommended values. Resumo: Justificativa e objetivos: A exposição ocupacional aos resíduos de gases anestésicos em salas de operação (SO) sem sistema ativo de exaustão tem sido associada a efeitos adversos à saúde. Assim, o objetivo do estudo foi comparar os resíduos dos anestésicos inalatórios isoflurano e sevoflurano em SO com e sem sistema de exaustão. Método: Concentrações residuais de isoflurano e sevoflurano foram mensuradas por analisador infravermelho em diferentes locais (próximo à área respiratória do auxiliar de enfermagem e do anestesiologista e próximo à estação de anestesia) e em dois momentos (30 e 120 min após o início da cirurgia) em ambos os tipos de SO. Resultados: Todas as concentrações de isoflurano e sevoflurano nas SO sem sistema de exaustão foram mais elevadas em relação ao valor limite recomendado pelos EUA (2 partes por milhão), independentemente do local e momento avaliados. Nas SO com sistema de exaustão, as concentrações médias de isoflurano ficaram dentro do limite de exposição, exceto para as mensurações próximas à estação de anestesia, independentemente dos momentos avaliados. Para o sevoflurano, as concentrações excederam o valor limite em todos locais de medição e nos dois momentos. Conclusões: A exposição a ambos os anestésicos excedeu o limite internacional nas SO sem sistema de exaustão. Nas SO com sistema de exaustão, as concentrações de sevoflurano, e em menor extensão as de isoflurano, excederam o valor limite recomendado. Dessa forma, o sistema de exaustão das SO analisado no presente estudo diminuiu as concentrações dos anestésicos, embora não tenha reduzido a valores internacionalmente recomendados. Keywords: Inhaled anesthetics, Operating rooms, Indoor air pollution, Occupational exposure, Palavras-chave: Anestésicos inalatórios, Salas cirúrgicas, Poluição do ar em ambientes fechados, Exposição ocupaciona

DNA damage in patients who underwent minimally invasive surgery under inhalation or intravenous anesthesia

Recent studies have demonstrated the genotoxicity of anesthetics in patients who have undergone surgery and in personnel who are occupationally exposed to anesthetics. However, these findings are controversial. Herein, we used the comet assay (single-cell gel electrophoresis) to investigate the genotoxic effects of two volatile compounds [isoflurane (ISF) and sevoflurane (SVF)] that are used in inhalation anesthesia, and of one intravenous (iv) anesthetic compound [propofol (PF)]. The groups consisted of 45 patients who underwent minimally invasive surgery that lasted at least 2 h. Patients were classified as physical status I using the criteria of the American Society of Anesthesiologists (ASA) and were randomly allocated to receive ISF. SVF or PF anesthesia. Venous blood samples were collected at three time points as follows: before the premedication and the induction of anesthesia (T(0)); 2 h after the beginning of anesthesia (T(1)); and on the day following surgery (T(2)). DNA damage (strand breaks and alkali-labile sites) was evaluated in peripheral blood lymphocytes. For each patient, one hundred nucleoids were analyzed per time point using a semi-automated image system. Patients did not differ with respect to their demographic characteristics, the duration of surgery, or the total doses of intraoperative drugs. The amount of DNA damage was not different among the three groups before anesthesia (T(0)). No statistically significant (p > 0.05) increase in DNA damage was detected during (T(1)) or after anesthesia (T(2)) using three different protocols (ISF, SVF or PF). In conclusion, general anesthesia with inhaled ISF and SVF or iv PF did not induce DNA strand breaks or alkali-labile sites in peripheral lymphocytes. Therefore, our results show that the genotoxic risk of these anesthetics, for healthy patients undergoing minimally invasive otorhinological surgery, is low or even absent. (C) 2011 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Evaluation of DNA damage and lipoperoxidation of propofol in patients undergoing elective surgery

Background and objectives Inhaled anaesthetics have been studied regarding their genotoxic and mutagenic potential in vivo. Propofol differs from volatile anaesthetics because it does not show mutagenic effects and it has been reported to be an antioxidant However, there are no studies with propofol and genotoxicity in vivo. The study aimed to evaluate the hypothesis that propofol is not genotoxic and it inhibits lipid peroxidation [malondialdehyde (MDA)] in patients undergoing propofol anaesthesia.Methods ASA physical status I patients scheduled for elective surgery, lasting at least 90 min, were enrolled in this study. Initially, the estimated plasma concentration of propofol was targeted at 4 mu g ml(-1) and then maintained at 2-4 mu g ml(-1) until the end of surgery. Haemodynamic data were determined at baseline (before premedication) and in conjunction with target-controlled infusion of propofol: after tracheal intubation, 30, 60 and 90 min after anaesthesia induction and at the end of the surgery. Venous blood samples were collected at baseline, after tracheal intubation, at the end of the surgery and on the postoperative first day for evaluating DNA damage in white blood cells (WBCs), by comet assay, and MDA levels.Results Haemodynamic data did not differ among times. No statistically significant differences were observed for the levels of DNA damage in WBCs, nor in plasma MDA, among the four times.Conclusion Propofol does not induce DNA damage in WBCs and does not alter MDA in plasma of patients. Eur J Anaesthesiol 26:654-660 (C) 2009 European Society of Anaesthesiology.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Comparison of inflammatory cytokine profiles in plasma of patients undergoing otorhinological surgery with propofol or isoflurane anesthesia

Objective and design: The effects of anesthetics on cytokine release in patients without comorbidities who undergo minor surgery are not well defined. We compared inflammatory cytokine profiles in adult patients undergoing minimally invasive surgery who received isoflurane or propofol anesthesia. Methods: Thirty-four patients without comorbidities undergoing minor surgery were randomly assigned to receive an inhaled anesthetic (isoflurane; n = 16) or an intravenous anesthetic (propofol; n = 18). Blood samples were drawn before premedication and anesthesia (T1), 120 min after anesthesia induction (T2), and on the first post-operative day (T3). Plasma concentrations of interleukins (IL-) 1β, 6, 8, 10 and 12 and tumor necrosis factor (TNF)-α were measured using flow cytometry. Results: The pro-inflammatory cytokine IL-6 was increased in the isoflurane group at T2 and T3 compared to T1 (P < 0.01). In the propofol group, IL-6 and IL-8 were significantly increased at T3 compared to T1. However, there were no significant differences in cytokine concentrations between the isoflurane and propofol groups. Conclusion: An inflammatory response occurred earlier in patients who received an inhaled agent compared with an intravenous anesthetic, but no differences in plasma cytokine profiles were evident between isoflurane and propofol anesthesia in patients without comorbidities undergoing minimally invasive surgeries. © 2013 Springer Basel