Brain DNA damaging effects of volatile anesthetics and 1 and 2 Gy gamma irradiation in vivo: Preliminary results

Author:

Benković Vesna1,Milić Mirta2ORCID,Oršolić Nada1,Horvat Knežević Anica1,Brozović Gordana34,Borojević Nikola5

Affiliation:

1. Faculty of Science, University of Zagreb, Zagreb, Croatia

2. Mutagenesis Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia

3. Department of Anesthesiology, Reanimatology and ICU, University Hospital for Tumors, Sestre Milosrdnice University Hospital Centre, Zagreb, Croatia

4. Faculty of Dental Medicine and Health, University of Osijek, Osijek, Croatia

5. Warrington and Halton Teaching Hospitals NHS Foundation Trust, Warrington, UK

Abstract

Although both can cause DNA damage, the combined impact of volatile anesthetics halothane/sevoflurane/isoflurane and radiotherapeutic exposure on sensitive brain cells in vivo has not been previously analyzed. Healthy Swiss albino male mice (240 in total, 48 groups) were exposed to either halothane/sevoflurane/isoflurane therapeutic doses alone (2 h); 1 or 2 gray of gamma radiation alone; or combined exposure. Frontal lobe brain samples from five animals were taken immediately and 2, 6, and 24 h after exposure. DNA damage and cellular repair index were analyzed using the alkaline comet assay and the tail intensity parameter. Elevated tail intensity levels for sevoflurane/halothane were the highest at 6 h and returned to baseline within 24 h for sevoflurane, but not for halothane, while isoflurane treatment caused lower tail intensity than control values. Combined exposure demonstrated a slightly halothane/sevoflurane protective and isoflurane protective effect, which was stronger for 2 than for 1 gray. Cellular repair indices and tail intensity histograms indicated different modes of action in DNA damage creation. Isoflurane/sevoflurane/halothane preconditioning demonstrated protective effects in sensitive brain cells in vivo. Owing to the constant increases in the combined use of radiotherapy and volatile anesthetics, further studies should explore the mechanisms behind these effects, including longer and multiple exposure treatments and in vivo brain tumor models.

Funder

Institute for Medical Research and Occupational Health, Zagreb

University of Zagreb, Faculty of Science

Ministry of Science of Republic Croatia

Publisher

SAGE Publications

Subject

Health, Toxicology and Mutagenesis,Public Health, Environmental and Occupational Health,Toxicology

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