Neuroprotective effects of thymoquinone against ketamine -and MK-801-induced neurotoxicity in SH-SY5Y cells: From the perspective of glutamatergic dysfunction in schizophrenia

Abstract

Objective: Schizophrenia is a chronic disorder with approximately 1% prevalence and related to disrupted neurodevelopment process. It has been known that N-methyl D-Aspartate (NMDA) receptor antagonists such as ketamine and MK-801 mimic schizophrenia-like behaviors in rodents and cellular changes in cell culture. There are certain preliminary reports showing the beneficial effects of Nigella sativa L. extracts or its main active ingredient, thymoquinone, on psychiatric disorders. In our study, we aimed to investigate the neuroprotective effects of thymoquinone against ketamine- and MK-801- induced neurotoxicites, which may be relevant to schizophrenia. Methods: The neurotoxic concentrations of ketamine and MK-801, and non-toxic concentrations of thymoquinone were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test at the 24th hour of administrations in SH-SY5Y cells. Seven different concentrations of thymoquinone (0.5 µM, 1 µM, 2.5 µM, 5 µM, 10 µM, 20 µM, 30 µM) were tested against two different concentrations of ketamine (250 µg/ml, 500 µg/ml) and one concentration of MK-801 (100 µM).Results: Ketamine (250 µg/ml and 500 µg/ml) and MK-801 (100 µM) decreased (P<0.05) the cellular viabilities at the 24 hour of administrations. Thymoquinone pretreatment prevented (P<0.05) the decrease of cell viabilities against ketamine (250 µg/ml) and ketamine (500 µg/ml) at 1 uM, 2.5 µM, 5 µM, 10 µM, 20 µM, and 2.5 µM concentrations, respectively. Thymoquinone pretreatment also increased (P<0.05) cell viability compared to MK-801. Conclusion: We suggested that thymoquinone had neuroprotective effects on the NMDA receptor antagonists induced neurotoxicity and encourage researchers for further in vivo studies for schizophrenia.