engleski

Use of Human Neuroblastoma SH-SY5Y Cells to Evaluate Cytotoxic, Genotoxic and Oxidative Stress-Induced Effects of Codeine and Morphine

Codeine and morphine are alkaloids from the opioid family widely used as pain relief drugs or antitussive cough suppressant. Both drugs are found naturally in the poppy plant, Papaver somniferum. If misused or abused, neurobehavioral alterations, respiratory depression, constipation, sedation, tolerance, nausea, vomiting, itch, dry mouth and addiction may occur. While the current knowledge related to toxic effects of these opioids is limited, the aim of this study was to determine if they could induce a DNA damaging effect and oxidative stress response in human neuroblastoma SH-SY5Y cells. 24-h treatment with morphine and codeine at 1.56 μmol/L resulted with 80.84±4.14 and 85.82±3.85 % viable cells, respectively. These concentrations allowed genotoxicity testing using the alkaline comet assay, which resulted in a significant increase of primary DNA damage after both treatments versus negative control (median tail intensity 0.22 % DNA). At the same tested concentration, codeine exerted a slightly higher genotoxic potency towards SH-SY5Y cells (median tail intensity 2.25 %) than morphine (median tail intensity 1.07 % DNA). Differences in the observed DNA damage pattern could be attributed to specific interactions of the tested compounds with DNA, which affect their behavior during alkaline denaturation and electrophoresis. Codeine induced a significant decrease in glutathione (GSH) and a significant increase in the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT), whereas morphine induced a significant decrease in reactive oxygen species (ROS) production and SOD, and a significant increase in GPx and CAT activity when compared to controls. There was no significant impact of the investigated drugs on the levels of lipid peroxidation (MDA). Our results warrant further investigation to obtain insights into the mechanisms of toxic effects of codeine and morphine. Funding: This research 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’s grant number HrZZ- UIP-2017-05-7260.

opioids ; DNA damaging effect ; oxidative stress ; alkaline comet assay

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