Vitaminas B1, B6, B12 e Complexo B na prevenção da discinesia orofacial induzida por haloperidol em ratos : avaliação comportamental e mecanismos associados

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Ano de defesa: 2015
Autor(a) principal: Oliveira, Gersilene Valente de
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Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
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Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/15726
Resumo: Tardive dyskinesia (TD) is characterized by involuntary movements, mostly at lower face, near the mouth, with convulsion that can be light or hard. Is one severe disorder related, but restricted the antipsychotic therapy. Antipsychotic treatments above all the class of typical, like haloperidol (HAL) increase the risk of TD. The pathophysiology of TD is associated to a instability in neurotransmission system, such as dopaminergic and cholinergic, among others, as well as with oxidative instability mainly in brain areas related to the control of movement, as the striatum. B vitamins, in turn, show antioxidants effect and are cofactors to enzymes related to the synthesis of neurotransmitters. In this context, the present study aimed to determine the preventive effects of B1, B6, B12 vitamins or B complex against orofacial dyskinesia (OD) induced by HAL in rats. To do this male Wistar rats were intraperitoneally administered HAL (1 mg/kg, i.p.) for 21 days or concomitantly received HAL, B1 (60 mg/kg), B6 (60 mg/kg) or B12 (0,6 mg/kg) vitamin subcutaneously alone or in association. B complex consisted in the mix of 3 vitamins in equal proportions. One group of animals was administered with clozapine (25 mg/kg), an atypical antipsychotic not related to the development of OD. Behavioral tests were performed at the 1st, 7th and 21st days of drugs administration. The behavioral tests performed were locomotor activity, catalepsy and chewing vacuous movements. At 21st day the animals were sacrificed and had their brain areas dissected for neurochemical analysis. The results showed that HAL increased catalepsy time at 7th day and OD at 21st day. Administration of B vitamins (B1:B6:B12) alone or in association, together with HAL, prevented the development of OD and in a lower extension, catalepsy. Preventive effect of B vitamins was accompanied by restoration of the levels of reduced glutathione (GSH) and lipid peroxidation. Beyond the antioxidant effects, B vitamins increased the activity of the enzyme acetylcholinesterase (AChE) in all brain areas studied, with the maximum increase of activity observed in the hippocampus of animals co-administered with B12 vitamins and B vitamins cocktail. Clozapine did not induce OD and increase in the activity of AChE. Analysis of the expression of receptors and enzymes related to the synthesis of neurotransmitters in striatum by PCR-RT revealed that HAL increased the expression of the dopaminergic receptors D1 and D2 and reduce an expression of the muscarinic receptors M1. Haloperidol decreased the expression of tyrosine hydroxylase (TH), a limiting step for the synthesis of dopamine. Taken together the results suggest that B vitamins prevented changes induced by HAL, presenting thus a promising role as a preventive approach against HAL-induced OD.
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spelling Vitaminas B1, B6, B12 e Complexo B na prevenção da discinesia orofacial induzida por haloperidol em ratos : avaliação comportamental e mecanismos associadosB1, B6, B12 vitamins and B Complex in the prevention of orofacial dyskinesia induced by haloperidol in rats : behavioral assessment and associated mechanismsDiscinesiasHaloperidolClozapinaTardive dyskinesia (TD) is characterized by involuntary movements, mostly at lower face, near the mouth, with convulsion that can be light or hard. Is one severe disorder related, but restricted the antipsychotic therapy. Antipsychotic treatments above all the class of typical, like haloperidol (HAL) increase the risk of TD. The pathophysiology of TD is associated to a instability in neurotransmission system, such as dopaminergic and cholinergic, among others, as well as with oxidative instability mainly in brain areas related to the control of movement, as the striatum. B vitamins, in turn, show antioxidants effect and are cofactors to enzymes related to the synthesis of neurotransmitters. In this context, the present study aimed to determine the preventive effects of B1, B6, B12 vitamins or B complex against orofacial dyskinesia (OD) induced by HAL in rats. To do this male Wistar rats were intraperitoneally administered HAL (1 mg/kg, i.p.) for 21 days or concomitantly received HAL, B1 (60 mg/kg), B6 (60 mg/kg) or B12 (0,6 mg/kg) vitamin subcutaneously alone or in association. B complex consisted in the mix of 3 vitamins in equal proportions. One group of animals was administered with clozapine (25 mg/kg), an atypical antipsychotic not related to the development of OD. Behavioral tests were performed at the 1st, 7th and 21st days of drugs administration. The behavioral tests performed were locomotor activity, catalepsy and chewing vacuous movements. At 21st day the animals were sacrificed and had their brain areas dissected for neurochemical analysis. The results showed that HAL increased catalepsy time at 7th day and OD at 21st day. Administration of B vitamins (B1:B6:B12) alone or in association, together with HAL, prevented the development of OD and in a lower extension, catalepsy. Preventive effect of B vitamins was accompanied by restoration of the levels of reduced glutathione (GSH) and lipid peroxidation. Beyond the antioxidant effects, B vitamins increased the activity of the enzyme acetylcholinesterase (AChE) in all brain areas studied, with the maximum increase of activity observed in the hippocampus of animals co-administered with B12 vitamins and B vitamins cocktail. Clozapine did not induce OD and increase in the activity of AChE. Analysis of the expression of receptors and enzymes related to the synthesis of neurotransmitters in striatum by PCR-RT revealed that HAL increased the expression of the dopaminergic receptors D1 and D2 and reduce an expression of the muscarinic receptors M1. Haloperidol decreased the expression of tyrosine hydroxylase (TH), a limiting step for the synthesis of dopamine. Taken together the results suggest that B vitamins prevented changes induced by HAL, presenting thus a promising role as a preventive approach against HAL-induced OD.A Discinesia tardia (DT) é caracterizada por movimentos involuntários, principalmente na parte inferior da face, próximos da boca, com espasmos que podem ser leves ou severos. É uma alteração motora grave relacionada, mas não restrita à terapia antipsicótica. Tratamentos com antipsicóticos principalmente os da classe dos típicos, como o haloperidol (HAL) aumentam os riscos de DT. A fisiopatologia da DT é associada a um desequilíbrio em sistemas de neurotransmissão, dentre eles dopaminérgico e colinérgico, bem como com desequilíbrio oxidativo, principalmente em áreas cerebrais relacionadas ao controle do movimento, como o corpo estriado. As vitaminas (vit.) B, por sua vez, apresentam efeitos antioxidantes sendo cofatores para enzimas relacionadas à síntese de neurotransmissores. Neste contexto, o presente trabalho teve como objetivo determinar os efeitos preventivos das vit. B1, B6, B12 ou Complexo B na discinesia orofacial (DO) induzida por HAL em ratos. Foram utilizados ratos Wistar machos tratados por via intraperitoneal com HAL (1 mg/kg, i.p.) por 21 dias ou concomitantemente com HAL e as vit. B1 (60 mg/kg), B6 (60 mg/kg) ou B12 (0,6 mg/kg) por via subcutânea, sozinhas ou em associação (complexo B). O complexo B consistiu na mistura das 3 vitaminas em iguais proporções. Um grupo de animais foi administrado clozapina (25 mg/kg), um antipsicótico atípico não relacionado ao desenvolvimento de DO. Os testes comportamentais foram realizados após 30 minutos no 1º, 7º e 21º dias de administração das fármacos e consistiram na determinação da atividade locomotora, catalepsia e movimentos de mastigação no vazio. No 21° dia os animais foram sacrificados e retiradas áreas cerebrais para as análises neuroquímicas e de expressão para tirosina hidroxilase (TH), receptores dopaminérgicos D1 e D2 e receptor muscarínico M1. Os resultados mostraram que o HAL aumentou o tempo de catalepsia no dia 7 e causou DO no dia 21. A administração das vit. B (B1: B6: B12) sozinhas ou em associação, juntamente com HAL, preveniu o desenvolvimento de DO e em menor extensão da catalepsia. O efeito preventivo das vit. B foi acompanhado por restauração dos níveis de glutationa reduzida (GSH) e peroxidação lipídica. Além dos efeitos antioxidantes, as vit. B aumentaram a atividade da enzima acetilcolinesterase (AChE) em todas as áreas cerebrais estudadas, com o incremento máximo de atividade observada no hipocampo de animais co-tratados com vit. B12 e coquetel de vit. B. A clozapina não induziu DO e aumentou a atividade AChE semelhante para os grupos co-administrados com vit. B e HAL. A análise da expressão de receptores e enzimas relacionadas à síntese de neurotransmissores no corpo estriado por PCR-RT revelou que o HAL foi capaz de aumentar a expressão de receptores dopaminérgicos D1 e D2 e reduzir a expressão dos receptores muscarínicos M1. A expressão da tirosina hidroxilase (TH), passo limitante para a síntese de dopamina, se apresentou reduzida pelo HAL. Os dados sugerem que as vitamina do complexo B são capazes de prevenir as alterações induzidas pelo HAL apresentando, portanto, um papel promissor na prevenção de DO associada ao uso desta fármaco.Gaspar, Danielle MacêdoOliveira, Gersilene Valente de2016-03-23T13:08:17Z2016-03-23T13:08:17Z2015info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfOLIVEIRA, Gersilene Valente de. Vitaminas B1, B6, B12 e Complexo B na prevenção da discinesia orofacial induzida por haloperidol em ratos: avaliação comportamental e mecanismos associados. 2015. 120 f. Tese (Doutorado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2015.http://www.repositorio.ufc.br/handle/riufc/15726porreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2019-10-24T12:41:19Zoai:repositorio.ufc.br:riufc/15726Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-09-11T18:58:23.259653Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.none.fl_str_mv Vitaminas B1, B6, B12 e Complexo B na prevenção da discinesia orofacial induzida por haloperidol em ratos : avaliação comportamental e mecanismos associados
B1, B6, B12 vitamins and B Complex in the prevention of orofacial dyskinesia induced by haloperidol in rats : behavioral assessment and associated mechanisms
title Vitaminas B1, B6, B12 e Complexo B na prevenção da discinesia orofacial induzida por haloperidol em ratos : avaliação comportamental e mecanismos associados
spellingShingle Vitaminas B1, B6, B12 e Complexo B na prevenção da discinesia orofacial induzida por haloperidol em ratos : avaliação comportamental e mecanismos associados
Oliveira, Gersilene Valente de
Discinesias
Haloperidol
Clozapina
title_short Vitaminas B1, B6, B12 e Complexo B na prevenção da discinesia orofacial induzida por haloperidol em ratos : avaliação comportamental e mecanismos associados
title_full Vitaminas B1, B6, B12 e Complexo B na prevenção da discinesia orofacial induzida por haloperidol em ratos : avaliação comportamental e mecanismos associados
title_fullStr Vitaminas B1, B6, B12 e Complexo B na prevenção da discinesia orofacial induzida por haloperidol em ratos : avaliação comportamental e mecanismos associados
title_full_unstemmed Vitaminas B1, B6, B12 e Complexo B na prevenção da discinesia orofacial induzida por haloperidol em ratos : avaliação comportamental e mecanismos associados
title_sort Vitaminas B1, B6, B12 e Complexo B na prevenção da discinesia orofacial induzida por haloperidol em ratos : avaliação comportamental e mecanismos associados
author Oliveira, Gersilene Valente de
author_facet Oliveira, Gersilene Valente de
author_role author
dc.contributor.none.fl_str_mv Gaspar, Danielle Macêdo
dc.contributor.author.fl_str_mv Oliveira, Gersilene Valente de
dc.subject.por.fl_str_mv Discinesias
Haloperidol
Clozapina
topic Discinesias
Haloperidol
Clozapina
description Tardive dyskinesia (TD) is characterized by involuntary movements, mostly at lower face, near the mouth, with convulsion that can be light or hard. Is one severe disorder related, but restricted the antipsychotic therapy. Antipsychotic treatments above all the class of typical, like haloperidol (HAL) increase the risk of TD. The pathophysiology of TD is associated to a instability in neurotransmission system, such as dopaminergic and cholinergic, among others, as well as with oxidative instability mainly in brain areas related to the control of movement, as the striatum. B vitamins, in turn, show antioxidants effect and are cofactors to enzymes related to the synthesis of neurotransmitters. In this context, the present study aimed to determine the preventive effects of B1, B6, B12 vitamins or B complex against orofacial dyskinesia (OD) induced by HAL in rats. To do this male Wistar rats were intraperitoneally administered HAL (1 mg/kg, i.p.) for 21 days or concomitantly received HAL, B1 (60 mg/kg), B6 (60 mg/kg) or B12 (0,6 mg/kg) vitamin subcutaneously alone or in association. B complex consisted in the mix of 3 vitamins in equal proportions. One group of animals was administered with clozapine (25 mg/kg), an atypical antipsychotic not related to the development of OD. Behavioral tests were performed at the 1st, 7th and 21st days of drugs administration. The behavioral tests performed were locomotor activity, catalepsy and chewing vacuous movements. At 21st day the animals were sacrificed and had their brain areas dissected for neurochemical analysis. The results showed that HAL increased catalepsy time at 7th day and OD at 21st day. Administration of B vitamins (B1:B6:B12) alone or in association, together with HAL, prevented the development of OD and in a lower extension, catalepsy. Preventive effect of B vitamins was accompanied by restoration of the levels of reduced glutathione (GSH) and lipid peroxidation. Beyond the antioxidant effects, B vitamins increased the activity of the enzyme acetylcholinesterase (AChE) in all brain areas studied, with the maximum increase of activity observed in the hippocampus of animals co-administered with B12 vitamins and B vitamins cocktail. Clozapine did not induce OD and increase in the activity of AChE. Analysis of the expression of receptors and enzymes related to the synthesis of neurotransmitters in striatum by PCR-RT revealed that HAL increased the expression of the dopaminergic receptors D1 and D2 and reduce an expression of the muscarinic receptors M1. Haloperidol decreased the expression of tyrosine hydroxylase (TH), a limiting step for the synthesis of dopamine. Taken together the results suggest that B vitamins prevented changes induced by HAL, presenting thus a promising role as a preventive approach against HAL-induced OD.
publishDate 2015
dc.date.none.fl_str_mv 2015
2016-03-23T13:08:17Z
2016-03-23T13:08:17Z
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dc.identifier.uri.fl_str_mv OLIVEIRA, Gersilene Valente de. Vitaminas B1, B6, B12 e Complexo B na prevenção da discinesia orofacial induzida por haloperidol em ratos: avaliação comportamental e mecanismos associados. 2015. 120 f. Tese (Doutorado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2015.
http://www.repositorio.ufc.br/handle/riufc/15726
identifier_str_mv OLIVEIRA, Gersilene Valente de. Vitaminas B1, B6, B12 e Complexo B na prevenção da discinesia orofacial induzida por haloperidol em ratos: avaliação comportamental e mecanismos associados. 2015. 120 f. Tese (Doutorado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2015.
url http://www.repositorio.ufc.br/handle/riufc/15726
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