Simvastatin markedly alters locomotor behavior parameters and induces mortality in planarians

Statins are widely prescribed medications for the management of dyslipidemias. Although their clinical efficacy is responsible for reducing cardiovascular diseases, side effects, including cognitive impairment, have been reported. Since the neurological effects are not well understood, this study aimed to evaluate the influence of simvastatin (Sim), atorvastatin (Ator) and rosuvastatin (Rosu) on locomotor behavior parameters in planarians. Planarians (Girardia tigrina), which are plathelminths used for neuropharmacology and neurotoxicology studies, were pre-incubated for 1 h, 6 h or directly exposed to each statin (10-50 μM), and had their locomotor activity recorded for 5 min. Then, the parameters of average speed, average acceleration, exploration rate, and mobility rate were analyzed using the ToxTrac software. Survival rate (%) was also assessed. Sim caused significant increases in average speed, average acceleration and mobility rate of the planarians. Otherwise, these parameters, as well as the exploration rate, were strongly decreased by Sim after 1 h of pre-incubation. In contrast, Ator and Rosu presented less intense effects, highlighting a decrease in the locomotor activity of planarians previously pre-incubated for 6 h with Ator. Additionally, the planarians exposed to Sim, but not to Ator and Rosu, exhibited a short and irregular trajectory, characterized by atypical behaviors, such as head shaking, frequent turning, repetitive contortions and scrunching. Finally, all planarians died after 30 h of expositions to 50 μM Sim, whereas 75 % after 48 h of exposition to 25 μM Sim. Taken together, the results indicate that Sim promoted neurotoxic activity in planarians.