In vitro assessment of the cytotoxic, genotoxic and oxidative stress effects of a synthetic cannabinoid jwh-018 in human sh-sy5y neuronal cells

Abuse of new generation synthetic cannabinoids has been increasing due to THC like cannabimimetic effects on Central Nervous System and serious side effects even fatalities due to synthetic cannabinoids abuse have been reported. JWH-018, one of the first generation of new syntethic cannabinoids, shows 4-5 times higher binding affinity to CB1 receptor which is responsible for euphoria and psychoactive effects of marijuhana. There are very few studies investigating the cytotoxicity mechanisms of synthetic cannabinoids. In this study, JWH-018's cytotoxic, apoptotic, genotoxic effects and effects on oxidative stress parameters on neuroblastoma SH-SY5Y cell line were investigated. Firstly, MTT, NRU and LDH assays were performed to determine cytotoxicity and IC50 value. According to MTT, NRU and LDH test results, there were no statistically significant change in cell viability observed. Evaluating the oxidative stress parameters, glutathione (GSH), thiobarbituric acid reactive substances (TBARS), protein carbonyl levels and glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) acitivities were measured. For genotoxicity evaluation, Comet assay was performed. For apoptosiz/necrosis ratio determination, Annexin V/PI assay was performed. There was a statistically significant decrease in GSH levels, decrease in glutathione reductase and catalase enzyme activities and increase in protein carbonylation levels. There was no statistically significant change in apoptosis/necrosis ratio and comet assay observed due to JWH-018 exposure. Key Words: Synthetic cannabinoid, JWH-018, Neuroblastoma SH-SY5Y, In vitro cytotoxicity, Oxidative stress