Avaliação do efeito do pentilenotetrazol e 4-aminopiridina sobre parâmetros de sobrevivência, locomotores e bioquímicos em Drosophila melanogaster

Abstract

Epilepsy, a neurological chronic disorder, could be experimentally induced by pentylenetetrazole (PTZ) or 4-aminopyridine (4-AP). Importantly, both PTZ and 4-AP are known to be able to cause oxidative stress (OS), which is associated with epileptic condition. However, the effect of PTZ and 4-AP in Drosophila melanogaster remains to be better understand. Accordingly, the use of D. melanogaster as alternative/complementary models could be suitable to better understand the subjacent mechanism(s) to the biological activity of both drugs. So, in this study we investigated the effect of both PTZ and 4-AP on survival, locomotor performance and biochemical markers (both in body and head) in D. melanogaster. Wild-type adult flies of 7 days old were exposed, in a dietary regimen, to PTZ (60 mM) or 4-AP (20 mM) for 48 hours. 4-AP-fed flies presented a higher incidence of mortality and a worse performance in the open-field test compared to non-treated flies. The 4-AP toxicity was associated to a significant increase in the reactive species (RS) and in protein carbonyl (PC) content in body and head. The 4-AP exposure also resulted in a significant increase in catalase and in acetylcholinesterase (AChE) activity, as well as a significant decrease in MTT reduction in body. In turn, superoxide dismutase (SOD) was differently modulated in body and head of 4-AP-treated flies. On the other hand, PTZ exposure resulted in a significant increase in RS, TBARS, PC and in catalase activity, and a significant decrease in MTT reduction in body. The PTZ exposure was also associated to a significant increase in AChE activity both in body and head. The SOD activity was also differently modulated in body and head of PTZ-treated flies. Collectively, our findings highlight that 4-AP and PTZ differently affected the survival, locomotor activity and biochemical markers in D. melanogaster, as well 11 11

as confirms the utility of this model to investigate mechanism(s) subjacent to the toxicological activity of PTZ or 4-AP. Accordingly, our observations highlight the potential use of this experimental animal model to investigate safer and more effective therapies in the treatment of neurological disorders, with emphasis in strategies to counteract changes associated to exposure to both drugs.