Cavalcanti, B.C., Magalhães, I.L., Barreto, F.S., Dos Santos, C.A.L., de Araújo Monteiro, A.A., de Andrade Neto, J.B., Magalhães, H.I.F., de Oliveira Ferreira, J.R., Barros, L.M., de Moraes, M.O. (2026). Toxicological aspects of haloperidol in human lung fibroblasts (MRC-5 cells) and Drosophila melanogaster as an alternative model: analysis of cytotoxic, genotoxic and oxidative stress potential.  Food Chem. Toxicol. 215(): 116178.

FBrf0265774

Research paper

Haloperidol (HP), an antipsychotic, has been associated with toxicological effects beyond its therapeutic actions. This study investigated its cytotoxic, genotoxic, mutagenic and oxidative stress potential in human lung fibroblasts (MRC-5 cells) and in Drosophila melanogaster as an alternative in vivo model. In MRC-5 cells, HP reduced viability and increased lactate dehydrogenase release, accompanied by lipid and protein oxidation. HP also induced DNA strand breaks and oxidative DNA lesions (Fpg-sensitive sites), and elevated micronucleus formation with greater effects in the presence of the S9 fraction, suggesting the involvement of reactive metabolites. Furthermore, no mutagenicity was observed in Salmonella typhimurium. In D. melanogaster, chronic exposure to HP (7 days of treatment) impaired locomotor activity and decreased sulfhydryl group levels only at the highest concentration. These data on redox imbalance in D. melanogaster suggest there may be compensatory antioxidant mechanisms involved in the overall defense against oxidative stress. Molecular docking analysis revealed a stable interaction between HP and the mitochondrial complex I of D. melanogaster, suggesting that HP may cause disruption of electron transport and energy production. Collectively, these results demonstrate that HP triggers cytotoxic, genotoxic and mutagenic responses in MRC-5 cells along with redox imbalance in mammalian cells and in D. melanogaster.