High anesthetic exposure leads to oxidative damage and gene expression changes in physicians during medical residency: a cohort study.

Evaluation of the possible toxic effects of occupational exposure to anesthetics is of great importance, and the literature is limited in assessing the possible association between occupational exposure to anesthetics and oxidative stress and genetic damage. To contribute to the gap of knowledge in relation to cause-effect, this cohort study was the first to monitor exposure assessment and to evaluate oxidative stress, DNA damage, and gene expression (OGG1, NRF2, HO-1, and TP53) in young adult physicians occupationally exposed to the most modern halogenated anesthetics (currently the commonly used inhalational anesthetics worldwide) in addition to nitrous oxide gas during the medical residency period. Therefore, the physicians were evaluated before the beginning of the medical residency (before the exposure to anesthetics-baseline), during (1 1/2 year) and at the end (2 1/2 years) of the medical residency. Anesthetic air monitoring was performed in operating rooms without adequate ventilation/scavenging systems, and biological samples were analyzed for lipid peroxidation, protein carbonyl content, primary and oxidative DNA damage, antioxidant enzymes and plasma antioxidant capacity, and expression of some key genes. The results showed induction of lipid peroxidation, DNA damage, glutathione peroxidase activity, and NRF2 and OGG1 expression up to the end of medical residency. Plasma antioxidant capacity progressively increased throughout medical residency; oxidative DNA damage levels started to increase during medical residency and were higher at the end of residency than at baseline. Protein carbonyls increased during but not at the end of medical residency compared to baseline. The antioxidant enzyme superoxide dismutase activity remained lower than baseline during and at the end of medical residency, and HO-1 (related to antioxidant defense) expression was downregulated at the end of medical residency. Additionally, anesthetic concentrations were above international recommendations. In conclusion, high concentrations of anesthetic in the workplace induce oxidative stress, gene expression modulation, and genotoxicity in physicians during their specialization period.

High anesthetic (isoflurane) indoor pollution is associated with genetic instability, cytotoxicity, and proliferative alterations in professionals working in a veterinary hospital.

This is the first study to monitor anesthetic pollution in veterinary operating rooms (VOR) and assess the toxicological impact of the inhalational anesthetic isoflurane (exposed group) compared to matched volunteers (control group). DNA damage was evaluated in mononuclear cells by the comet assay while genetic instability (including micronucleus-MN), cell proliferation, and cell death markers were assessed by the buccal MN cytome assay. Residual isoflurane concentrations in VOR (air monitoring) lacking the scavenging system were assessed by infrared spectrophotometry; the mean concentration was 11 ppm (≥ 5 times above the international recommended threshold). Comet assay results did not differ between groups; however, both younger exposed professionals (with higher week workload) compared to older individuals exposed for the same period and older professionals with greater time of exposure (years) compared to those in the same age group with fewer years of exposure presented higher DNA damage. The exposed group had a higher frequency of MN, nuclear buds, binucleated cells, karyorrhexis, and karyolysis and a lower frequency of basal cells than the control group. Exposed women were more vulnerable to genetic instability and proliferative index; exposed men presented more cytotoxicity. High WAG exposure has deleterious effects on exposed professionals.

Measurement of anesthetic pollution in veterinary operating rooms for small animals: Isoflurane pollution in a university veterinary hospital.

INTRODUCTION: Inhaled anesthetics are used worldwide for anesthesia maintenance both in human and veterinary operating rooms. High concentrations of waste anesthetic gases can lead to health risks for the professionals exposed. Considering that anesthetic pollution in a veterinary surgical center in developing countries is unknown, this study aimed, for the first time, to measure the residual concentration of isoflurane in the air of operating rooms for small animals in a Brazilian university hospital. METHOD: Residual isoflurane concentrations were measured by an infrared analyzer at the following sites: corner opposite to anesthesia machine; breathing zones of the surgeon, anesthesiologist, and patient (animal); and in front of the anesthesia machine at three time points, that is, 5, 30 and 120 minutes after anesthesia induction. RESULTS: Mean residual isoflurane concentrations gradually increased in the corner opposite to anesthesia machine and in the breathing zones of the surgeon and the anesthesiologist (p <  0.05). There was an increase at 30 minutes and 120 minutes when compared to the initial time points in the animal's breathing zone, and in the front of the anesthesia machine (p <  0.05). There was no significant difference at measurement sites regardless of the moment of assessment. CONCLUSION: This study reported high residual isoflurane concentrations in veterinary operating rooms without an exhaust system, which exceeds the limit recommended by an international agency. Based on our findings, there is urgent need to implement exhaust systems to reduce anesthetic pollution and decrease occupational exposure.

Hepatotoxic and neuroendocrine effects in physicians occupationally exposed to most modern halogenated anesthetics and nitrous oxide.

The lack of data on hepatic and hormonal markers for occupational exposure to most modern halogenated anesthetics has stimulated our research, which assessed liver enzymes, high-sensitivity C-reactive protein (hs-CRP) and neuroendocrine response. The study investigated 106 physicians who were categorized in an exposed group (primarily exposed to isoflurane and sevoflurane and less to desflurane and nitrous oxide) as well as as a control group. Anesthetic air monitoring was performed, and biological samples were analyzed for the most important liver enzymes, hs-CRP, adrenocorticotrophic hormone, cortisol and prolactin. No biomarkers were significantly different between the groups. Exposed males showed significant increases in cortisol and prolactin compared to unexposed males. However, values were within the reference ranges, and 22 % of exposed males versus 5 % of unexposed males exhibited higher prolactin values above the reference range. This study suggests that occupational exposure to the most commonly used inhalational anesthetics is not associated with hepatotoxicity or neurohormonal changes.

Gene and systemic inflammatory effects and neuroendocrine response in surgical patients anesthetized with desflurane-nitrous oxide or desflurane-nitrous oxide-free: A randomized trial.

There is growing interest in assessing possible immunotoxicological effects in anesthetized patients. There are controversial findings concerning the effect of nitrous oxide (N2O) anesthetic gas effect on inflammatory response. We tested the hypothesis that N2O associated with desflurane (inhalational anesthetic) was likely to worsen neuro-immune-endocrine effects when compared with desflurane alone in this randomized trial. The primary endpoint of this study was to evaluate the systemic proinflammatory interleukin (IL)-6, and the secondary endpoints included other systemic (IL-1ß, TNF-α, IL-8, IL-10, IL-17A and high-sensitivity C-reactive protein - hs-CRP) and genetic inflammatory markers (NF-kB, IL-6 and COX-2) as well as hormones (adrenocorticotropic hormone, cortisol and prolactin) comparing patients undergoing minor surgery with or without N2O-desflurane. As a second aim, we assessed whether there were changes in the neuro-immune-endocrine profiles within each group. Blood samples were collected before anesthesia, 90 min after anesthesia induction, and the day after surgery. We assessed serum cytokines using a cytometric bead array and hs-CRP by chemiluminescent immunoassay. Expression of three proinflammatory transcripts was assessed by real-time quantitative polymerase chain reaction, and neuroendocrine hormones were detected by chemiluminescent microparticle immunoenzymatic assay. There were no significant between-group differences for any analyzed biomarkers. However, there was a significant increase in: (a) systemic IL-6 and hs-CRP values one day after surgery in both groups and (b) prolactin levels in the intraoperative period compared to baseline and postoperative period levels for both groups. In conclusion, N2O does not impair the inflammatory profile and neuroendocrine response compared to patients who receive only desflurane anesthesia.

Genetic instability assessed by telomere length and micronucleus in physicians exposed to anesthetics.

This study evaluated both telomere length (TL) and micronucleus (MN) as indicators of genome instability in 40 anesthesiologists occupationally exposed to anesthetics and in 40 physicians without occupational exposure to anesthetics who were matched by age, sex, and lifestyle. Blood and buccal samples were collected from both groups at the same period. Anesthetic exposure assessment was performed. The studied groups were assessed regarding relative TL by quantitative polymerase chain reaction and MN by buccal MN assay. Mean trace concentrations of anesthetics were below two parts per million. No significant differences between groups were found for both biomarkers. However, MN frequency was slightly increased (1.9-fold; p = .094) in the exposed group compared to the control group and in the exposed males (2.4-fold; p = .090) compared to unexposed males. TL and age showed a significant negative correlation. Anesthetic occupational exposure below recommended levels is not associated with changes in TL and MN in anesthesiologists.

Inflammation and DNA damage induction in surgical patients maintained with desflurane anesthesia.

The use of anesthetics during surgical interventions may contribute to disorders in the perioperative period. Desflurane is the newest volatile halogenated anesthetic to be introduced in clinical practice. Considering that inflammation and genotoxicity are linked events, and that little is known regarding possible genetic and inflammatory effects of desflurane in surgical patients, this study evaluated DNA damage, systemic inflammatory cytokines and related gene expression in adult patients without comorbidities who underwent minor otorhinological surgeries under general anesthesia maintained with the inhalational anesthetic desflurane. This study involved a self-controlled design in which venous blood samples were collected from subjects before anesthesia administration and after the surgical procedure. The comet assay was applied to assess DNA lesions, while the cytokines IL-1ß, IL-6, IL-8, IL-10, IL-17A and TNF-α were evaluated by flow cytometry. A genotoxic effect was observed (p = 0.027), and pro-inflammatory IL-6 and IL-8 levels were significantly increased after surgery (p = 0.001 and p = 0.02, respectively), whereas the levels of the other cytokines did not significantly change. Considering that serum IL-6 and IL-8 were increased, we further evaluated IL-6 and IL-8 gene expression by quantitative real-time polymerase chain reaction (qPCR). However, IL-6 and IL-8 gene expression was unaltered (p >  0.05). In conclusion, anesthetic maintenance with the modern agent desflurane during minor surgeries led to genotoxic and inflammatory effects without altering the expression of inflammation related-genes the day after surgery in patients without comorbidities.

Monitoring early cell damage in physicians who are occupationally exposed to inhalational anesthetics.

Worldwide, millions of professionals who work in operating rooms are occupationally exposed to inhalational anesthetics. Thus, the potential health effects of the continuous exposure to inhalational anesthetics on individuals in the operating room remain a subject of debate. Human biomonitoring is a potentially useful tool for assessing the health of exposed professionals. No report has yet evaluated the possible cytotoxic and genotoxic effects of the most commonly used inhalational anesthetics on young professionals who are occupationally exposed. Considering the importance of this issue, we monitored physicians who were exposed to inhalational anesthetics during their first year of a medical residency program to evaluate the possible early damage events. Twenty-six young physicians who had been occupationally exposed to the anesthetics isoflurane, sevoflurane, desflurane, and nitrous oxide and who worked in operating rooms using modern anesthesia workstations during their medical residency program, participated in this study. Blood samples were evaluated before the start of the program (before the exposure), and after 1/2 year and 1 year of exposure. We monitored the subjects by assessing the cytotoxicity (early apoptosis and loss of the mitochondrial membrane potential) using flow cytometry and genotoxicity using the comet assay. No significant changes were observed in the biomarkers of cytotoxicity or genotoxicity (p > 0.05). Thus, biomonitoring showed that short-term exposure to inhalational anesthetics did not induce early cell damage during the first year of medical residency. Based on the results, brief occupational exposure to anesthetics does not induce either cytotoxicity or genotoxicity in mononuclear cells under the conditions of this study. Thus, young physicians should undergo additional biomonitoring at the beginning of their careers to determine possible toxic effects on their cells and genetic material, and further investigations are warranted to determine whether a longer exposure to inhalational anesthetics results in mitochondrial depolarization, apoptosis and DNA breaks.

Comparison of DNA Damage and Oxidative Stress in Patients Anesthetized With Desflurane Associated or Not With Nitrous Oxide: A Prospective Randomized Clinical Trial.

BACKGROUND: Little is known about the effects of desflurane associated or not with nitrous oxide (N2O) on oxidative stress and patient genetic material. The aim of this study was to compare the effects of anesthesia maintained with desflurane associated or not with N2O on DNA damage (as a primary outcome) and oxidative stress (as a secondary outcome) in patients who underwent an elective minimally invasive surgery. METHODS: This prospective randomized clinical trial analyzed 40 patients of both sexes with an American Society of Anesthesiologists physical status I who were 18-50 years of age and scheduled for septoplasty. The patients were randomly allocated into 2 groups according to anesthesia maintenance as follows: desflurane (n = 20) or desflurane/N2O (n = 20). Blood samples were collected before anesthesia (T1 = baseline), 1.5 hours after anesthesia induction (T2), and on the morning of the postoperative first day (T3). Basal and oxidative DNA damage (determined using formamidopyrimidine DNA glycosylase to detect oxidized purines and endonuclease III to detect oxidized pyrimidines) were evaluated using the comet assay. Oxidative stress markers were evaluated based on lipid peroxidation (by assessing 4-hydroxynonenal and 8-iso-prostaglandin F2α [8-isoprostane] using enzyme linked immunosorbent immunoassay), protein carbonyls (assessed by enzyme linked immunosorbent immunoassay), and antioxidant defense (ferric-reducing antioxidant power by spectrophotometry). The effect size was expressed as the mean differences between groups and the corresponding 95% confidence interval (CI). RESULTS: There was no significant mean difference between groups in relation to DNA damage (-1.7 [95% CI, -7.0 to 3.5]), oxidized DNA pyrimidines (-1.8 [95% CI, -12.5 to 8.9]) and purines (-1.9 [95% CI, -13.9 to 10.1]), 4-hydroxynonenal (-0.2 [95% CI, -2.8 to 2.4]), 8-isoprostane (549 [95% CI, -2378 to 3476]), protein carbonyls (0.2 [95% CI, -2.1 to 2.3]), or ferric-reducing antioxidant power (24 [95% CI, -52.0 to 117.2]). CONCLUSIONS: The coadministration of 60% N2O with desflurane did not seem to impair the effects on DNA or the redox status compared with desflurane anesthesia, suggesting that both studied anesthetic techniques can be suitable options for healthy individuals who undergo minimally invasive surgery lasting at least 1.5 hours. However, due to the low power of the study, more research is necessary to confirm our findings.

Genotoxicity assessment of fipronil (frontline plus®) in Canis familiaris / Avaliação de genotoxicidade do fipronil (frontline plus®) em cães

Fipronil is a pesticide widely used for controlling fleas and ticks in domestic animals, and its short-term exposure can lead to serious effects on animals. However, the possible genotoxic effect of this compound has not been investigated in target animals. Based on the hypothesis that fipronil can induce genotoxicity, this study evaluated the effect of fipronil on DNA damage in peripheral blood cells. For that purpose, ten dogs of both sexes were used in the study. The product (6.7mg/kg) was applied on the dorsal neck region of each animal. Peripheral blood samples were collected immediately prior to application of the product, and at 3, 8 and 24 hours after the application. Samples were processed for comet assay. No statistically significant differences were found among the four time points. The current study suggests for the first time that a single exposure to this pesticide does not induce systemic genotoxic effect in dogs.(AU)

O fipronil é um inseticida/herbicida amplamente utilizado para controle de pulgas e carrapatos em animais domésticos. Sua exposição a curto prazo tem acarretado efeitos deletérios em animais. Entretanto, o possível efeito genotóxico deste composto ainda não foi investigado em animais alvo. Baseando-se na hipótese de que o fipronil pode induzir genotoxicidade, o presente estudo avaliou o efeito deletério do fipronil no material genético de células de sangue periférico. Para isso, dez cães sadios, de ambos os sexos, foram utilizados neste estudo. O produto (6,7mg/kg) foi aplicado na região dorsal do pescoço de cada animal. As amostras de sangue foram coletadas imediatamente antes da aplicação do produto (controle) e após três, oito e 24 horas da aplicação. As amostras foram imediatamente processadas para condução do teste do cometa, a fim de se avaliar os danos basais no DNA. Não houve diferença significativa entre os quatro momentos de coleta em relação aos danos no material genético. O estudo sugere, pela primeira vez, que uma exposição única a este pesticida não induz efeito genotóxico sistêmico em cães.(AU)

Occupational exposure to anesthetics leads to genomic instability, cytotoxicity and proliferative changes.

Data on the genotoxic and mutagenic effects of occupational exposure to the most frequently used volatile anesthetics are limited and controversial. The current study is the first to evaluate genomic instability, cell death and proliferative index in exfoliated buccal cells (EBC) from anesthesiologists. We also evaluated DNA damage and determined the concentrations of the anesthetic gases most commonly used in operating rooms. This study was conducted on physicians who were allocated into two groups: the exposed group, which consisted of anesthesiologists who had been exposed to waste anesthetic gases (isoflurane, sevoflurane, desflurane and nitrous oxide - N2O) for at least two years; and the control group, which consisted of non-exposed physicians matched for age, sex and lifestyle with the exposed group. Venous blood and EBC samples were collected from all participants. Basal DNA damage was evaluated in lymphocytes by the comet assay, whereas the buccal micronucleus (MN) cytome (BMCyt) assay was applied to evaluate genotoxic and cytotoxic effects. The concentrations of N2O and anesthetics were measured via a portable infrared spectrophotometer. The average concentration of waste gases was greater than 5 parts per million (ppm) for all of the halogenated anesthetics and was more than 170ppm for N2O, expressed as a time-weighted average. There was no significant difference between the groups in relation to lymphocyte DNA damage. The exposed group had higher frequencies of MN, karyorrhexis and pyknosis, and a lower frequency of basal cells compared with the control group. In conclusion, exposure to modern waste anesthetic gases did not induce systemic DNA damage, but it did result in genomic instability, cytotoxicity and proliferative changes, which were detected in the EBC of anesthesiologists. Thus, these professionals can be considered at risk for developing genetic alterations resulting from occupational exposure to these gases, suggesting the need to minimize this exposure.

Evaluation of genotoxicity of general anesthesia maintained with desflurane in patients under minor surgery.

There is controversy over the genotoxic effects of volatile anesthetics. The available literature on the genotoxicity of desflurane, one of the newest volatile halogenated agents used for general anesthesia maintenance, is scarce. This study aimed to evaluate the genotoxic potential of desflurane in 15 patients without comorbidities, of both sexes, who underwent minor surgeries lasting at least 90 min. Patients enrolled in the study received desflurane anesthesia (6%); blood samples were collected before anesthesia induction (T0), 90 min after the beginning of anesthesia (T1), and on the day following surgery (T2). DNA damage was evaluated in lymphocytes using the alkaline comet assay. We found statistically significant increases in DNA damage in T2 samples compared to T0. The findings suggest that desflurane anesthesia induces DNA strand breaks/alkali-labile sites on the day after minimally invasive surgery in healthy patients.