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Anesthetic Ketamine-Induced DNA Damage in Different Cell Types In Vivo

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Abstract

The use of a combination of ketamine and xylazine is broadly used either for anesthesia or euthanasia in rodent animal models in research. However, the genotoxicity and mutagenic effects of these drugs are unknown. Therefore, the aim of this study was to evaluate these effects to help the understanding of elevated values in negative controls in genotoxic/mutagenic assays. Sixty CF-1 mice were divided into ten groups of six mice per group: negative control (saline), positive control (doxorubicin, 40 mg/kg), ketamine at 80 mg/kg and xylazine at 10 mg/kg, ketamine at 100 mg/kg and xylazine at 10 mg/kg, ketamine at 140 mg/kg and xylazine at 8 mg/kg, ketamine at 80 mg/kg, ketamine at 100 mg/kg, ketamine at 140 mg/kg, xylazine at 8 mg/kg, and xylazine at 10 mg/kg. After drug induction, the blood cells were analyzed at 1, 12, and 24 h by the comet assay, while the brain cortex, liver, and kidney cells were verified just at 24 h by the comet assay and bone marrow was tested at 24 h by micronucleus test. The positive control was significantly different in relation to the negative control in all times and tissue analyzed. The dose of ketamine at 140 mg/kg plus xylazine at 8 mg/kg and only ketamine at 140 mg/kg exhibited a genotoxic effect in blood and brain cells at all the times analyzed. The doses of ketamine at 80 and 100 mg/kg in association or not with xylazine showed increased DNA damage at 1 and 12 h, but this effect was reversed after 24 h of drug administration. The liver, kidney, and bone marrow cells of animals treated with ketamine or xylazine isolated or combined did not differ when compared with the negative control. Then, our findings emphasize the necessity of more studies that prove safety of the ketamine use, since that anesthetic can be able to induce false-negative results in genotoxic experimental studies.

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Acknowledgments

The authors would like to thank the Graduate Program in Health Sciences (PPGCS) at the University of Southern Santa Catarina for the use of their equipment, in order to carry out this research.

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Authors and Affiliations

  1. Laboratory of Molecular and Cellular Biology, Graduate Program of Health Sciences, Department of Health Sciences, University of Southern Santa Catarina, UNESC, 1105, Universitária Rd, 88806000, Criciúma, SC, Brazil

    Daniela Dimer Leffa, Bruno Nunes Bristot, Adriani Paganini Damiani, Gabriela Daminelli Borges, Francine Daumann, Gabriela Maria Zambon, Gabriela Elibio Fagundes & Vanessa Moraes de Andrade

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  1. Daniela Dimer Leffa
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  2. Bruno Nunes Bristot
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Correspondence to Daniela Dimer Leffa.

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The authors are grateful for the financial support from the following funding bodies: National Council of Technological and Scientific Development (CNPq) and University of Southern Santa Catarina (UNESC).

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Leffa, D.D., Bristot, B.N., Damiani, A.P. et al. Anesthetic Ketamine-Induced DNA Damage in Different Cell Types In Vivo. Mol Neurobiol 53, 5575–5581 (2016). https://doi.org/10.1007/s12035-015-9476-8

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