Influência do antipsicótico atípico ziprasidona sobre o metabolismo de lipídios e comportamento do nematódeo Caenorhabditis elegans

Abstract

The metabolic syndrome is the major side effect related to atypicalantipsychotics use. Even from this drug class, ziprasidone has been rarely associated as generating these effects mainly to weight gain. Nevertheless, the differential molecular pathways of this drug remain largely unknown. Considering the numerous difficulties to perform depth studies related to metabolism, the present study was proposed to evaluate the profile of lipid accumulation and possible behavioral changes in a new experimental model, the nematode Caenorhabditiselegans. Our results showed ziprasidone was effective to decrease the fluorescence marked by Nile Red, BODIPY and LipidTox in intestinal cells of the nematode C. elegans comparing to the control (0.16% Dimethyl sulfoxide). This effect was observed only under 24 h of treatment (L4 larval stage until adult). The ziprasidone did not altered the behaviors related to energetic balance such as pharynx pumping, defecation cycles and movement of C. elegans compared to the control group. However, there was an important reduction in egg-production, egg-laying and bodylength of the nematodes exposed to ziprasidone without any changes in the progression of larval stages. Moreover, the components of serotoninergic pathway appear not to be involved in the effect caused by ziprasidone on the levels of Nile Red fluorescence. On the other hand, we detected a modulation in the effects generated by ziprasidone on the fluorescence exerted by exogenous tyramine monoamine exposition, as well as the transcription factors DAF-16 and CREB observed by reversing the profile of fluorescence in mutants for these factors to the levels of control. Considering these results, it is suggested that ziprasidone altersreproductive behavior, morphology and lipid reserves in the intestinal cells of the nematode C. elegans. We still identify the influence of the tyramine monoamine and the transcription factors DAF-16 and CREB in the ziprasidone action on the lipid accumulation in the intestinal cells of this nematode.