Promethazine provokes behavioral alterations and disrupts redox homeostasis in planarians

Promethazine is a first-generation H1 antihistamine that affects a variety of targets in the vertebrate nervous system, which explains its sedative effects and other neurological actions that are not fully clarified. To better understand the neurobiological activity of promethazine, the aim of this study was to evaluate the effects of promethazine on behavioral and redox homeostasis parameters in planarians (Girardia tigrina), in order to better understand its potential neurobiological effects. Planarians were pre-incubated for 1 h, 6 h or directly exposed to different concentrations of promethazine (5, 10, 25, and 50 µM) and, subsequently, the behavioral and redox homeostasis parameters were assessed. Locomotor activity was recorded for 5 min and analyzed using ToxTrac software, measuring parameters such as average speed, average acceleration, exploration rate, mobility rate, distance and trajectory. Redox homeostasis markers were also assessed, including malondialdehyde (MDA) levels, sulfhydryl content, reduced glutathione (GSH) concentrations, and superoxide dismutase (SOD) activity. Low concentrations of promethazine (5 and 10 µM) increased locomotor activity, while higher concentrations (25 and 50 µM) led to a significant reduction in average speed and exploration rate. Additionally, 1 h pre-incubation in the presence of promethazine increased MDA levels, GSH concentrations, and SOD activity, without affecting sulfhydryl content, suggesting lipid peroxidation and changes in antioxidant response in planarians. Overall, the study demonstrates that promethazine significantly alters planarian behavior and disrupts redox homeostasis, indicating a strong neuroactive response in planarians.