Toxicogenetics, oxidative, inflammatory and metabolomics evaluation of exposure to sevoflurane: an experimental study

Abstract

Sevoflurane is an inhalational halogenated anesthetic routinely applied for the induction and/or maintenance of general anesthesia. However, little is known about its toxic potential since inclinical research the evaluations are performed without separating the effects of anesthesia fromthose related to surgery. To contribute to this important gap in the literature, the current proposal will evaluate the isolated effect of acute exposure (hours) to three different concentrations of sevoflurane (dose-response curve; 3 groups exposed), using Swiss mice, for toxicogenetics, oxidative, inflammatory and metabolomics assessment. Mice without exposure will constitute the negative control group whereas the positive control group will have DNA damage-induction. DNA damage (comet assay) and inflammatory markers (flow cytometry) will be assessed in blood samples as well as the detection of sevoflurane/metabolite (internal biomarker) by gas chromatography and metabolomics by flow infusion electrospray ionization high resolution mass spectrometry. Oxidative stress will be assessed by lipid peroxidation, carbonyl proteins and antioxidant capacity. Histopathological analysis will be evaluated in lung and liver, in which genetic damage will also be evaluated. The micronucleus assay (mutagenicity/cytotoxicity) will be evaluated in bone marrow cells. Expression of genes related to metabolism, maintenance ofcellular homeostasis, repair of oxidative damage and antioxidant response will be detected (liverand lung). Note that the proposal has national and international collaborations (collaboration with the United Kingdom, where the doctorate student plans to conduct the metabolomics analysis). Considering the relevance and originality of the study, greater knowledge will be obtained about possible deleterious effects and mechanisms of toxicity of acute exposure to sevoflurane.It is noteworthy that this research project already has financial support from FAPESP n° 2022/10697-8 for its realization.