PROMETHAZINE PROVOKES BEHAVIORAL ALTERATIONS AND INDUCES OXIDATIVE STRESS IN PLANARIANS

Resumo

INTRODUCTION: Promethazine is a first-generation H1 antihistamine with wide distributionin the central nervous system, which accounts for its sedative effect and other neurologicalactions that are not yet fully understood. OBJECTIVES: Therefore, the aim of this study wasto evaluate the effects of promethazine on behavioral and oxidative stress parameters inplanarians (Girardia tigrina), in order to better understand the potential neurobiological effectsof this drug. MATERIALS AND METHODS: The use of this animal model does not requireapproval from the Ethics Committee on Animal Use, as planarians belong to the phylumPlatyhelminthes, in accordance with the Brazilian Guidelines for the Care and Use of Animalsin Research Activities (RN 55/2022). Planarians were pre-incubated in the presence ofpromethazine for 1 hour at concentrations of 5 to 50 µM, and subsequently the behavioral andoxidative stress parameters were assessed. The oxidative stress parameters measured were themalondialdehyde (MDA) levels, sulfhydryl content, reduced glutathione (GSH) concentrationsand superoxide dismutase (SOD) activity. Furthermore, the behavioral parameters evaluatedwere the average speed, average acceleration, exploration rate, mobility rate and distancetraveled, which were analyzed using the ToxTrac software after recording the locomotoractivity of each planarian for 5 minutes. RESULTS: It was observed that planarians exposedto lower concentrations of promethazine (5 and 10 µM) presented an increase in average speed,average acceleration, exploration rate, mobility rate, and distance traveled. On the other hand,at higher drug concentrations, especially 50 µM, planarians showed a reduction in theseparameters, indicating decreased locomotor activity. It was also found that exposition topromethazine significantly increased MDA levels, GSH concentrations and SOD activity,without altering sulfhydryl content, suggesting lipid peroxidation and changes of antioxidantactivity in planarians. CONCLUSIONS: It is concluded that promethazine significantly alteredplanarian behavior, with low concentrations leading to increase locomotor activity, while higherconcentrations caused a decrease. These data may be, at least in part, related to oxidative stressinduction. Finally, the results suggest that promethazine exhibits strong neurobiologicalactivity, with potential neurotoxic effects in planarians.