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Master's Dissertation
DOI
https://doi.org/10.11606/D.10.2009.tde-17022009-103524
Document
Author
Full name
Ana Paula Martins
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Spinosa, Helenice de Souza (President)
Florio, Jorge Camilo
Lebrun, Ivo
Title in Portuguese
Efeitos neurocomportamentais do fipronil administrado em dose única a ratos
Keywords in Portuguese
Comportamento
Convulsão
Fipronil
GABA
Neurotransmissão
Abstract in Portuguese
O fipronil é um inseticida fenilpirazol de amplo espectro, empregado na Medicina Veterinária e na Agricultura para o controle de pragas; é um potente inibidor do canal de cloreto ligado ao ácido gama aminobutírico (GABA), um dos neurotransmissores responsáveis por efeitos inibitórios no sistema nervoso central (SNC) de mamíferos. Embora vários estudos procurem compreender os mecanismos da toxicidade neuronal dos praguicidas em mamíferos, há poucos relacionados aos efeitos neurocomportamentais. Neste trabalho estudou-se os efeitos da exposição aguda a ao fipronil, utilizando-se modelos comportamentais ligados ao sistema GABAérgico: campo-aberto (CA), labirinto em cruz elevado (LCE), dose convulsivante mínima (DCM) com picrotoxina e pentilenotetrazol, e avaliação dos níveis cerebrais de alguns neurotransmissores e metabólitos. Ratos Wistar machos receberam, por via intragástrica (gavage), dose única de fipronil (1,0; 10,0; 30,0 ou 100,0 mg/Kg) ou água destilada 1 mL/Kg. No CA, uma hora após o tratamento, houve redução significante da distância percorrida, da velocidade média, do tempo em movimento e do número de levantamentos nos animais tratados. No LCE, observou-se diminuição da distância percorrida e número de entradas nos braços fechados e diminuição do número de movimentos iniciados na arena, nos animais tratados. Quanto às convulsões, foi observada redução significante apenas na DCM de pentilenotetrazol em animais expostos a maior dose de fipronil. Uma hora após o tratamento não foram observadas alterações relevantes nos níveis dos neurotransmissores (noradrenalina; dopamina, serotonina e GABA) e seus metabólitos no córtex, no hipotálamo e no striatum. Finalizando, os resultados do presente estudo mostraram que ratos expostos a dose única de fipronil apresentaram alterações comportamentais, caracterizadas por redução da atividade motora no campo aberto, no labirinto em cruz elevado e na dose convulsivante mínima do pentilenotetrazol. Além disso, a maior dose de fipronil (100,0 mg/Kg) causou a morte de 60% dos ratos, num período entre 24 horas a 7 dias após a exposição oral. Esses efeitos comportamentais do fipronil não puderam ser atribuídos a um único sistema de neurotransmissão central.
Title in English
Neurobehavioral effects of acute fipronil administration in rats
Keywords in English
Behavior
Fipronil
GABA
Neurotrasmission
Seizure
Abstract in English
The Fipronil is a phenylpyrazole insecticide with broad spectrum, both in Veterinary Medicine, and in Agriculture it has been used for the control of nuisances, is a potent inhibitor of chloride channel connected to the gamma aminobutyric acid (GABA), one of the neurotransmitters responsible for inhibitory effects on the central nervous system (CNS) of mammals. Although several studies try to understand the mechanism of neuronal toxicity of pesticide in mammalian, there are few studies related to neurobehavioral effects. Thus, the present study investigated the effects of fipronil acute exposure, being observed some behaviors models connected to GABAergic system, as open field, elevated plus maze (EPM), as well as in the seizures induced by picrotoxinin and pentylenotetrazole and determinate the brain levels of some neurotransmitter and metabolic levels. Male Wistar rats received by intragastric (gavage), single dose of fipronil (1.0; 10.0; 30.0 or 100.0 mg/Kg) or distilled water. In open field, one hour after treatment, there was a significant reduction of distance moved, average speed, time moving and the number of surveys in treated animals. In the EPM, it was observed decrease in the distance moved, in the number of entries in the closed arms and decrease the number of started movements in the arena, in treated animals. As for seizures, a significant decrease was observed only in minimum convulsant dose of pentylenotetrazole in animals exposed to higher dose of fipronil. One hour after treatment were not observed any relevant changes in the levels of neurotransmitters (norepinephrine, dopamine, serotonin and GABA) and its metabolites in the cortex, the hypothalamus and the striatum. Finally, the results of this study showed that rats exposed to single dose of fipronil showed behavioral changes, characterized by reduction of motor activity in the open field, in the elevated plus-maze and the minimum convulsant dose of pentyletetrazole. Moreover, the higher dose of fipronil (100.0 mg/Kg) caused the death of 60% of rats, over a period from 24 hours to 7 days after oral exposure. These behavioral effects of fipronil could not be attributed to a single system of central neurotransmission.
 
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Publishing Date
2009-04-03
 
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