Veterinarians exposed to inhaled anesthetic present chromosome damage, apoptosis and cell cycle changes.

This cross-sectional study evaluated, for the first time, DNA damage, viability, and cell death of lymphocytes and cell cycle phases of mononuclear and polymorphonuclear cells in veterinarians exposed to the volatile anesthetic isoflurane. Veterinarians who were occupationally exposed to isoflurane (exposed group; n = 20) and matched-unexposed individuals (volunteers without occupational exposure; n = 20) were enrolled in the study. DNA damage was assessed in lymphocytes by micronucleus (MN) and phosphorylated histone gamma-H2AX (γ-H2AX). Cell viability, cytotoxicity, and the cell cycle were evaluated by flow cytometry. Isoflurane was detected in urine samples by headspace gas chromatography-mass spectrometry. Compared with unexposed subjects, veterinarians occupationally exposed to isoflurane (25.7 ± 23.7 µg/L urine) presented statistically higher MN frequencies, lymphocytic apoptosis rates, and numbers of polymorphonuclear cells in the G0/G1 stage. Additionally, the exposed group presented statistically lower proportions of viable lymphocytes and G2/M polymorphonuclear cells. Our findings indicate that veterinarians who are frequently exposed to inhaled anesthetic exhibit chromosomal and cell damage in addition to changes in peripheral blood cell proliferation.

Modulation of gene expression and influence of gene polymorphisms related to genotoxicity and redox status on occupational exposure to inhaled anesthetics.

The extensive use of inhalational anesthetics contributes to both indoor and outdoor (environmental) pollution. The influence of genetic susceptibility on DNA damage and oxidative stress and the possible modulation of gene expression have not yet been investigated upon occupational exposure to waste anesthetic gases (WAGs). This study assessed 8-oxoguanine DNA glycosylase 1 (OGG1) and superoxide dismutase 2 (SOD2) gene expression, which are related to oxidized DNA repair and antioxidant capacity, respectively, and the influence of their polymorphisms (OGG1 rs1052133 and SOD2 rs4880) in 100 professionals highly exposed to WAGs and 93 unexposed volunteers (control group). Additionally, X-ray repair cross complementing 1 (XRCC1 rs25487 and rs1799782) and ataxia telangiectasia mutated (ATM rs600931) gene polymorphisms as well as genetic instability (micronucleus-MN and nuclear bud-NBUD) and oxidative stress (malondialdehyde-MDA and ferric reducing antioxidant power-FRAP) biomarkers were assessed in the groups (control and exposed) and in the subgroups of the exposed group according to job occupation (anesthesiologists versus surgeons/technicians). Except for the ATM TT controls (associated with increased FRAP), there were no influences of OGG1, XRCC1, ATM, and SOD2 polymorphisms on MN, NBUD, MDA, and FRAP values in exposed or control subjects. No significant difference in the expression of either gene evaluated (OGG1 and SOD2) was found between the exposed and control groups. Increased OGG1 expression was observed among OGG1 -/Cys individuals only in the control group. Among the exposed group, anesthesiologists had a greater duration of WAG exposure (both h/week and years) than surgeons/technicians, which was associated with increased MDA and decreased antioxidant capacity (FRAP) and SOD2 expression (redox status). Higher expression of OGG1 was found in -/Cys surgeons/technicians than in anesthesiologists with the same genotype. Increased antioxidant capacity was noted in the surgeons/technicians carrying the ATM T allele and in those carrying XRCC1 -/Gln. Increased MN was influenced by OGG1 -/Cys in surgeons/technicians. Anesthesiologists with ATM CC exhibited increased MN, and those carrying the C allele (CC/CT genotype) exhibited increased NBUD. SOD2 polymorphism did not seem to be relevant for WAG exposure. These findings contribute to advancing the knowledge on genetic susceptibility/gene expression/genetic instability/oxidative stress, including differences in job occupation considering the workload, in response to occupational exposure to WAGs.

Evaluation of genetic instability, oxidative stress, and metabolism-related gene polymorphisms in workers exposed to waste anesthetic gases.

Professionals who work in operating rooms (ORs) may be exposed daily to waste anesthetic gases (WAGs) due to the use of inhalational anesthetics. Considering the controversial findings related to genetic damage and redox status in addition to a lack of knowledge about the effect of polymorphisms in genes related to phase I and II detoxification upon occupational exposure to WAGs, this cross-sectional study is the first to jointly evaluate biomarkers of genetic instability, oxidative stress, and susceptibility genes in professionals occupationally exposed to high trace amounts of halogenated (≥ 7 ppm) and nitrous oxide (165 ppm) anesthetics in ORs and in individuals not exposed to WAGs (control group). Elevated rates of buccal micronucleus (MN) and nuclear bud (NBUD) were observed in the exposure group and in professionals exposed aged more than 30 years. Exposed males showed a higher antioxidant capacity, as determined by the ferric reducing antioxidant power (FRAP), than exposed females; exposed females had higher frequencies of MN and NBUD than nonexposed females. Genetic instability (MN) was observed in professionals with greater weekly WAG exposure, and those exposed for longer durations (years) exhibited oxidative stress (increased lipid peroxidation and decreased FRAP). Polymorphisms in metabolic genes (cytochrome P450 2E1 (CYP2E1) and glutathione S-transferases (GSTs)) did not exert an effect, except for the effects of the GSTP1 (rs1695) AG/GG polymorphism on FRAP (both groups) and GSTP1 AG/GG and GSTT1 null polymorphisms, which were associated with greater FRAP values in exposed males. Minimizing WAG exposure is necessary to reduce impacts on healthcare workers.

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.

Spontaneous abortion in women occupationally exposed to inhalational anesthetics: a critical systematic review.

Occupational exposure to inhalational anesthetics has been associated with health problems, including reproductive issues. Considering the scarcity and outdated nature of reviews concerning this relevant topic, which has implications for indoor pollution/environmental science/public health, this critical review aimed to systematically evaluate whether exposure to inhalational anesthetics is associated with abortion. Seven databases were searched with no language or year restrictions. Of the 3881 search results, 18 observational studies were included. Some studies demonstrated a significant association between occupational exposure to inhalational anesthetics and spontaneous abortion, especially among professionals who work for longer periods and/or in an environment without gas scavenging/ventilation systems, which may favor the occurrence of abortion in this population. Due to considerable heterogeneity and limitations, it cannot be concluded whether an association exists between occupational exposure to anesthetics and the occurrence of abortion. However, more well-designed studies should be performed, especially in less economically developed countries that do not have access to quality anesthetic gas scavenging/ventilation systems, thereby bringing this issue into sharp focus. This review highlights the need for scientific knowledge in this area and the extensive use of scavenging equipment and in the workplace to minimize exposure and reduce the risk of abortion.

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.

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.