Molecular and toxicogenetic safety profile of short-term nitrous oxide anesthesia in surgical patients
Juliana R Lara1, Flávia R Nogueira1, C-Y Oliver Chen2
1São Paulo State University (UNESP), Medical School, Division of Anesthesiology, GENOTOX Lab, Botucatu, Brazil.
Background:
Nitrous oxide (N2O) is a widely used anesthetic; however, its potential to compromise genomic stability by disrupting vitamin B12 and folate metabolism remains a critical concern in clinical molecular biology. Since N2O can oxidize cobalamin, it may theoretically impair the methionine synthase pathway, leading to DNA damage. Thus, this study aimed to evaluate the toxicogenetic impact-DNA damage and gene expression-and the metabolic profile of vitamins B9 and B12, homocysteine (HCY) and micronutrients/antioxidants in patients undergoing short-term N2O anesthesia.
Methods And Results:
Adult surgical patients without comorbidities (n = 18/group) were assessed at: pre-anesthesia, during anesthesia (1.5 h exposure), and 24 h post-anesthesia. Both groups received desflurane, with one also receiving N2O. The primary focus was on DNA strand breaks (comet assay) and the transcriptional levels (RT-qPCR) of repair (OGG1 and XRCC1) and antioxidant (HO-1) genes, followed by HPLC and chemiluminescence analysis of metabolic markers (HCY and antioxidants, vitamins B9 and B12). N2O exposure did not modulate the mRNA expression of any of the studied genes, nor did it alter HCY, vitamin levels or antioxidants (p > 0.05). A transient, group-independent increase in DNA damage was observed post-anesthesia, suggesting a primary response to surgical stress rather than the anesthetic agent.
Conclusions:
Our study provides high-evidence molecular data demonstrating that 1.5 h of N2O exposure is safe for genomic integrity and vitamin B-related metabolism in healthy individuals. These findings are clinically relevant as they validate the continued use of N2O in minimally invasive procedures without the risk of acute toxicogenetic or metabolic impairment.
Insights
Short-term nitrous oxide (N2O) anesthesia is safe for genomic stability and vitamin metabolism in healthy adults. The anesthetic did not cause DNA damage or alter key metabolic markers during minimally invasive procedures.
Area of Science:
- Anesthesiology
- Molecular Biology
- Clinical Biochemistry
Background:
- Nitrous oxide (N2O) anesthesia raises concerns regarding genomic stability due to potential disruption of vitamin B12 and folate metabolism.
- N2O's ability to oxidize cobalamin may impair methionine synthase, theoretically leading to DNA damage.
Purpose of the Study:
- To evaluate the toxicogenetic impact (DNA damage, gene expression) and metabolic profile (vitamins B9, B12, homocysteine, antioxidants) of short-term N2O anesthesia.
- To assess the safety of N2O regarding genomic integrity and vitamin metabolism in patients undergoing anesthesia.
Main Methods:
- Adult surgical patients (n=18/group) received desflurane, with one group also receiving N2O for 1.5 hours.
- Assessed DNA strand breaks (comet assay), gene expression (RT-qPCR for OGG1, XRCC1, HO-1), and metabolic markers (HPLC, chemiluminescence).
- Measurements taken pre-anesthesia, during anesthesia, and 24 hours post-anesthesia.
Main Results:
- N2O exposure did not affect mRNA expression of repair or antioxidant genes.
- No significant alterations in homocysteine, vitamin B9, vitamin B12, or antioxidant levels were observed.
- A transient, surgery-related increase in DNA damage occurred, independent of N2O exposure.
Conclusions:
- 1.5 hours of N2O anesthesia is safe for genomic integrity and vitamin B metabolism in healthy individuals.
- Findings support the continued use of N2O in minimally invasive procedures.
- No acute toxicogenetic or metabolic impairment was detected with short-term N2O use.
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