The role of mitochondrial dysfunction and calcium dysregulation in 2C-I and 25I-NBOMe-induced neurotoxicity.
Chemico-biological interactions April 25, 2025 Eva Gil-Martins, Fernando Cagide, Ana Borer et al. 4 citations
25I-NBOMe is significantly more cytotoxic than 2C-I in differentiated SH-SY5Y cells and primary rat cortical cultures, likely due to its higher lipophilicity. Both drugs cause severe mitochondrial dysfunction, including decreased ATP levels and mitochondrial membrane depolarization, without significant changes in reactive oxygen or nitrogen species. 25I-NBOMe also elevates intracellular calcium levels. Apoptosis occurs with both drugs, but 2C-I additionally induces autophagy and strong caspase-3 activation, suggesting caspase-3-dependent apoptosis, while 25I-NBOMe may trigger caspase-3-independent apoptosis through calcium dysregulation and direct mitochondrial damage. Mitochondrial dysfunction and calcium dysregulation are central to the neurotoxicity of these NPS.