Sevoflurane Induces DNA Damage Whereas Isoflurane Leads to Higher Antioxidative Status in Anesthetized Rats

Rocha, Thalita; Dias‐Junior, Carlos A.; Possomato-Vieira, José Sérgio; Gonçalves-Rizzi, Victor Hugo; Nogueira, Flávia R.; Souza, Kátina M.; Braz, Leandro Gobbo; Braz, Mariana Gobbo

doi:10.1155/2015/264971

Cited by 20 publications

(21 citation statements)

References 45 publications

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“…In this study, the use of isoflurane is a potentially confounding factor because it is thought to have antioxidant effects in and of itself (62–67). This claim is somewhat controversial, however, with other studies showing a prooxidant effect of isoflurane (62–67). The experiments performed herein were not designed to resolve this conflict.…”

Section: Discussionmentioning

confidence: 99%

In vivoimaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome

et al. 2017

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Hippocampus oxidative stress is considered pathogenic in neurodegenerative diseases, such as Alzheimer disease (AD), and in neurodevelopmental disorders, such as Angelman syndrome (AS). Yet clinical benefits of antioxidant treatment for these diseases remain unclear because conventional imaging methods are unable to guide management of therapies in specific hippocampus subfields that underlie abnormal behavior. Excessive production of paramagnetic free radicals in nonhippocampus brain tissue can be measured as a greater-than-normal 1/ that is quenchable with antioxidant as measured by quench-assisted (Quest) MRI. Here, we further test this approach in phantoms, and we present proof-of-concept data in models of AD-like and AS hippocampus oxidative stress that also exhibit impaired spatial learning and memory. AD-like models showed an abnormal gradient along the CA1 dorsal-ventral axis of excessive free radical production as measured by Quest MRI, and redox-sensitive calcium dysregulation as measured by manganese-enhanced MRI and electrophysiology. In the AS model, abnormally high free radical levels were observed in dorsal and ventral CA1. Quest MRI is a promising paradigm for bridging brain subfield oxidative stress and behavior in animal models and in human patients to better manage antioxidant therapy in devastating neurodegenerative and neurodevelopmental diseases.-Berkowitz, B. A., Lenning, J., Khetarpal, N., Tran, C., Wu, J. Y., Berri, A. M., Dernay, K., Haacke, E. M., Shafie-Khorassani, F., Podolsky, R. H., Gant, J. C., Maimaiti, S., Thibault, O., Murphy, G. G., Bennett, B. M., Roberts, R. imaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome.

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Section: Discussionmentioning

confidence: 99%

In vivoimaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome

et al. 2017

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“…We have found a significant increase in the S-phase duration of the neural progenitors exposed to sevoflurane (Figures 5(f) , 5(g) , and 5(h) ), further indicating the downregulation of differentiation in the fetal PFC. The S-phase duration is the main time for neural progenitors to control the quality of replicated DNA [ 27 ], and sevoflurane has been reported to significantly increase DNA damage in rodents [ 42 ]. Therefore, our observation of prolonged S-phase may also indicate that DNA replication of neural progenitors in the sevoflurane group is abnormal, pending further study.…”

Section: Discussionmentioning

confidence: 99%

Maternal Sevoflurane Exposure Causes Abnormal Development of Fetal Prefrontal Cortex and Induces Cognitive Dysfunction in Offspring

Song

Ling

Peng

et al. 2017

Stem Cells International

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Maternal sevoflurane exposure during pregnancy is associated with increased risk for behavioral deficits in offspring. Several studies indicated that neurogenesis abnormality may be responsible for the sevoflurane-induced neurotoxicity, but the concrete impact of sevoflurane on fetal brain development remains poorly understood. We aimed to investigate whether maternal sevoflurane exposure caused learning and memory impairment in offspring through inducing abnormal development of the fetal prefrontal cortex (PFC). Pregnant mice at gestational day 15.5 received 2.5% sevoflurane for 6 h. Learning function of the offspring was evaluated with the Morris water maze test at postnatal day 30. Brain tissues of fetal mice were subjected to immunofluorescence staining to assess differentiation, proliferation, and cell cycle dynamics of the fetal PFC. We found that maternal sevoflurane anesthesia impaired learning ability in offspring through inhibiting deep-layer immature neuron output and neuronal progenitor replication. With the assessment of cell cycle dynamics, we established that these effects were mediated through cell cycle arrest in neural progenitors. Our research has provided insights into the cell cycle-related mechanisms by which maternal sevoflurane exposure can induce neurodevelopmental abnormalities and learning dysfunction and appeals people to consider the neurotoxicity of anesthetics when considering the benefits and risks of nonobstetric surgical procedures.

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“…Rocha et al (35) provided evidence that sevoflurane induced genetic damage, whereas isoflurane increased systemic antioxidative status in Wistar rats exposed for 120 min. They suggest that possible mechanisms of sevoflurane genotoxicity include direct genotoxicity and/ or oxidative route by metabolism (35). Clinical studies indicated the absence of systemic DNA damage or oxidative DNA damage in patients under isoflurane anaesthesia (33).…”

Section: Discussionmentioning

confidence: 99%

“…Hirata et al (37) proved that isoflurane reduced myocardial infarction size by modulating mitochondrial ROS at clinical concentrations. Rocha et al (35) showed that rats anesthetised with isoflurane had a higher plasma antioxidative status. Concerning these findings, we presume that repair of DNA in rats treated with isoflurane in our study could be the consequence of the activation of antioxidative mechanisms in kidney cells.…”

Section: Discussionmentioning

confidence: 99%

Sevoflurane and isoflurane genotoxicity in kidney cells of mice

Brozović

Oršolić

Rozgaj

et al. 2017

Archives of Industrial Hygiene and Toxicology

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The aim of this study was to evaluate the DNA damage and repair in kidney cells of Swiss albino mice after repeated exposure to sevoflurane and isoflurane and compare their detrimental effects. We used the alkaline comet assay to establish the genetic damage and measured three parameters: tail length, tail moment, and tail intensity of comets. These parameters were measured immediately after exposure to the above mentioned inhalation anaesthetics, two hours, six hours, and 24 hours later and were compared with the control group. Mean values of all three parameters were significantly higher in experimental groups compared to the control group. DNA damage in kidney cells of mice exposed to sevoflurane increased continuously before it reached its peak 24 hours after exposure. Isoflurane induced the highest DNA damage two hours after exposure. Levels of DNA damage recorded 24 h after cessation of exposure to both tested compounds suggest that sevoflurane was slightly more genotoxic than isoflurane to kidney cells of mice. According to these results, the currently used volatile anaesthetics sevoflurane and isoflurane are able to damage DNA in kidney cells of mice. Such findings suggest a possibility for similar outcomes in humans and that fact must be taken into account in everyday clinical practice.

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Sevoflurane Induces DNA Damage Whereas Isoflurane Leads to Higher Antioxidative Status in Anesthetized Rats

Cited by 20 publications

References 45 publications

In vivoimaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome

In vivoimaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome

Maternal Sevoflurane Exposure Causes Abnormal Development of Fetal Prefrontal Cortex and Induces Cognitive Dysfunction in Offspring

Sevoflurane and isoflurane genotoxicity in kidney cells of mice

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