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Primary DNA damage in brain of mice exposed to anaesthetic isoflurane and ionizing irradiation in dose of 1 or 2 Gy

Due to fast sedation and stable patients’ conditions during the procedures when general anesthesia is necessary, volatile anesthetics (VA) are widely used, and among them, the most commonly used is isoflurane (ISO). Although considered safe, there are reports about its genotoxicity and mutagenicity in vitro, in vivo, and in clinical studies but with no consistent and even contradictory results, mostly considering the toxic and protective effects in brain cells. In the last decade, there is an increase in the number of different interventional and diagnostic radiology procedures requiring relative patient immobility either due to the procedure or due to different patients’ conditions. The use of novel irradiation techniques in different radiotherapy type (intraoperative radiotherapy, brachytherapy, fractionated and hypofractionated radiotherapy) demonstrated the possibility of receiving less radiation and fewer side effects, ionizing radiation (IR) is still considered a genotoxic, cytotoxic and mutagenic agent that can cause effects not only in a target area but also side effects in the surrounding healthy tissue (cells). Combined VA-IR effects have not been examined so far, although, according to the scientific literature, there is a possibility of their synergistic effects. ISO due to its influence on different receptors against pain, muscle relaxation, etc. demonstrated the highest impact on the brain cells. Therefore, we decided to test the influence of combined VA and single fractional IR dose exposure on the DNA damage levels in in vivo model. After ethical approvals, Swiss albino male mice (60±5 days old, 20-25g body weight), grouped in 6 main groups, with 5 animals each, were exposed to either 2.4 % ISO® isoflurane mixture with oxygen and air (50:50) for 2 hours or to 1 or 2 Gy whole-body γ-radiation exposure (60Co, Theratron Phoenix teletherapy unit, Atomic Energy Ltd, dose rate of 1.88 Gy/min) or their combination or served as a control group. Further subgroups were made according to the protocol established in our previous articles and animals were sacrificed immediately (0h), 2, 6, and 24h from the exposure, and brain cell single suspensions were prepared for DNA damage evaluation using alkaline comet assay, with duplicate samples per each animal, scoring 100 cells per each time point. In non-irradiated ISO samples, primary DNA damage levels, although slightly higher, did not significantly differ from control at all time points. IR only samples had significantly higher damage, with the dose increase. In both combined exposures, after 24 hours, ISO significantly decreased DNA damage levels, compared to IR samples and demonstrated its influence on increased velocity repair of the rest of IR damage. Adaptive response, by activating DNA repair mechanisms and the levels of reactive free oxygen radicals’ scavengers are the possible mechanisms of isoflurane protective effect but further research should be focused on determining the exact mechanisms.

isoflurane ; ionizing radiation ; comet assay ; Swiss albino mice

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