Ketamine-Ethanol Combination Decreases Reduced Glutathione Levels and Activates both Intrinsic and Extrinsic Apoptotic Pathways Prior to Neuronal Death in SH-SY5Y Cells.
Neurotoxicity research June 7, 2025 Felype Valentim Duarte Castelhano, Carolina Aparecida de Faria Almeida, Giulia de Assis Braz et al. 3 citations
Combining ketamine with ethanol triggers greater nerve cell death than either drug alone, acting through oxidative stress and two programmed-cell-death pathways. In human neuroblastoma cells, the lowest observed adverse-effect levels were 1 mM ketamine and 100 mM ethanol. After 48 hours, the combination produced a possible synergistic increase in late apoptotic cells. Glutathione levels fell within 6 hours, and glutathione-peroxidase activity rose in all groups. Only the combination increased glutathione reductase and glutathione S-transferase activities after 3 hours, along with elevated caspase-8 and Bax expression, signaling both extrinsic and intrinsic apoptosis. The findings suggest heightened neuronal damage risk from combined use, though limitations include enzyme-activity variability, reduced sample size for some markers, and use of an immortalized cell line.