Cytotoxicity evaluation of haloperidol, clozapine and a new molecule with antipsychotic potential, PT-31, in NIH-3T3 cells

• Autor(a) principal: Carlos Henrique Thomazi
• Data de Publicação: 2023
• Outros Autores: Alana Witt Hansen, Juliana Machado Kayser, Marina Griebeler Moreira, Marina Galdino da Rocha Pitta, Ivan da Rocha Pitta, Ana Luiza Ziulkoski, Andresa Heemann Betti
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Brazilian Journal of Pharmaceutical Sciences
• Texto Completo: https://www.revistas.usp.br/bjps/article/view/211957
• topic: Cytotoxicity; Clozapine; Haloperidol; NIH-3T3 cells; PT-31

Schizophrenia is an illness that affects 26 million people worldwide. However, conventional antipsychotics present side effects and toxicity, highlighting the need for new antipsychotics. We aimed to evaluate the cytotoxicity of haloperidol (HAL), clozapine (CLO), and a new molecule with antipsychotic potential, PT-31, in NIH-3T3 cells. The neutral red uptake assay and the MTT assay were performed to evaluate cell viability and mitochondrial activity, morphological changes were assessed, and intracellular reactive oxygen species (ROS) detection was performed. HAL and CLO (0.1 μM) showed a decrease in cell viability in the neutral red uptake assay and in the MTT assay. In addition, cell detachment, content decrease, rounding and cell death were also observed at 0.1 μM for both antipsychotics. An increase in ROS was observed for HAL (0.001, 0.01 and 1 μM) and CLO (0.01 and 1 μM). PT-31 did not alter cell viability in any of the assays, although it increased ROS at 0.01 and 1 μM. HAL and CLO present cytotoxicity at 0.1 μM, possibly through apoptosis and necrosis. In contrast, PT-31 does not present cytotoxicity to NIH-3T3 cells. Further studies must be performed for a better understanding of these mechanisms and the potential risk of conventional antipsychotics.