engleski

DNA damage and oxidative stress response in human neuroblastoma SH-SY5Y cell line exposed to ketamine

Background: Ketamine is a dissociative anaesthetic used in human and veterinary practice. The psychotropic properties of ketamine have been the main reason for its use also as a recreational drug in a variety of social settings, as well as in drug-facilitated sexual assault, owing to its dissociative and sedative properties. Ketamine abuse displays neurobehavioral alterations, such as depression, anxiety, cognition deficits, and schizophrenia. The exact mechanism of the neuronal damage following ketamine use is still unclear, but reactive oxygen species (ROS) may have an important role in the pathogenesis of neurological diseases. Also, data on genotoxic potentials are scarce and insufficient and do not allow a reasonable evaluation of its role in neurological impairment. Aim: The aim of this study was to determine the DNA damaging effect and oxidative stress response in human neuroblastoma SH-SY5Y cells treated with ketamine. Method: After a 24- hour treatment with a ketamine concentration that reduced cell viability up to 30 % and allowed genotoxicity testing, SH-SY5Y cells were subjected to a alkaline comet assay and biochemical assays that estimate oxidative stress. Results: For the assessments of ketamine toxicity, we selected the concentration of 6.25 μmol/L, which resulted in 78.59 ± 2.24 % of viable cells. Results of the alkaline comet assay showed significant increases of %DNA in tail, tail length and total comet area after ketamine treatment, compared to untreated cells. When compared to negative controls, the treated cells had a significant increase of malondialdehyde (MDA) level and significant decrease of glutathione (GSH) level as well as decreased catalase (CAT) and superoxide dismutase (SOD) activity. An increase in ROS level and decrease in glutathione peroxidase (GPx) activity were also observed, but the change was not significant. Discussion and Conclusion: Increased levels of DNA damage and the significant imbalance in the oxidative-antioxidant equilibrium detected in SH- SY5Y cells call for further studies on a wider range of doses and other experimental models. Funding: This study was supported by the programme of cooperation between the Institute for Medical Research and Occupational Health (Zagreb, Croatia) and the University North (Varaždin, Croatia) and the Croatian Science Foundation grant number HrZZ- UIP-2017-05-7260.

ketamine ; SH-SY5Y ; DNA damage ; oxidative stress

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