Estudo do mecanismo de ação antinociceptivo e avaliação histopatológica cerebral do (S)-(-)-álcool perílico em camundongos

Detalhes bibliográficos
Ano de defesa: 2013
Autor(a) principal: Benedito, Rubens Batista lattes
Orientador(a): Almeida, Reinaldo Nobrega de lattes
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal da Paraí­ba
Programa de Pós-Graduação: Programa de Pós Graduação em Produtos Naturais e Sintéticos Bioativos
Departamento: Farmacologia
País: BR
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: https://repositorio.ufpb.br/jspui/handle/tede/6802
Resumo: The perillyl alcohol (p-mentha-1,8-diene-7-ol) is a member of the family of monoterpenes found in plants of the genus Lavandula, Mentha, Cymbopogon, among others. It is known that perillyl alcohol (AP) has antinociceptive activity, but its mechanism of action remains unknown. In the present study was investigated the possible mechanism of action of PA using pharmacological antagonists and in vitro, and evaluated the histological level neurotoxicity in the hippocampus and striatum. The test of writhing induced by acetic acid was the protocol of choice for testing the monoterpene at a dose of 100 mg/kg against antagonists. The results show a reversal of the antinociceptive effect of PA (PA 3,4 ± 1,7 writhing) after pretreatment with naloxone (NLX+PA 10,4 ± 2,3 writhing) indicating the participation of the opioid system in its mechanism of action. Unlike naloxone, antagonists, muscarinic (atropine), adenosinergic (caffeine), dopamine (sulpiride), L-arginine - L-NNA and glibenclamide, were not able to reduce the effect of the PA front abdominal writhing. In the evaluation of in vitro antioxidant activity of the PA, three methodologies were employed, one to evaluate the effect of PA on lipid peroxidation in TBARS test and the other two to investigate its action as substance radical scavenging OH and NO. In all tests, the PA showed antioxidant activity, reducing by 70% the production of free radicals. As for histopathological evaluation, the PA did not cause significant tissue changes in both brain areas studied. Therefore, the results obtained in this study demonstrate that perillyl alcohol has an antinociceptive effect mediated by the opioid system and antioxidant mechanisms, without the direct participation of muscarinic systems, adenosinergic, dopaminergic, K+ATP channels and via L-arginine nitric oxide. The monoterpene also did not show significant neurotoxicity.
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spelling 2015-05-14T12:59:57Z2018-07-21T00:25:07Z2014-09-102018-07-21T00:25:07Z2013-09-27BENEDITO, Rubens Batista. Study of the mechanism of action antinociceptive and histopathological evaluation of the brain (s)-(-)-perillyl alcohol in mice. 2013. 109 f. Tese (Doutorado em Farmacologia) - Universidade Federal da Paraí­ba, João Pessoa, 2013.https://repositorio.ufpb.br/jspui/handle/tede/6802The perillyl alcohol (p-mentha-1,8-diene-7-ol) is a member of the family of monoterpenes found in plants of the genus Lavandula, Mentha, Cymbopogon, among others. It is known that perillyl alcohol (AP) has antinociceptive activity, but its mechanism of action remains unknown. In the present study was investigated the possible mechanism of action of PA using pharmacological antagonists and in vitro, and evaluated the histological level neurotoxicity in the hippocampus and striatum. The test of writhing induced by acetic acid was the protocol of choice for testing the monoterpene at a dose of 100 mg/kg against antagonists. The results show a reversal of the antinociceptive effect of PA (PA 3,4 ± 1,7 writhing) after pretreatment with naloxone (NLX+PA 10,4 ± 2,3 writhing) indicating the participation of the opioid system in its mechanism of action. Unlike naloxone, antagonists, muscarinic (atropine), adenosinergic (caffeine), dopamine (sulpiride), L-arginine - L-NNA and glibenclamide, were not able to reduce the effect of the PA front abdominal writhing. In the evaluation of in vitro antioxidant activity of the PA, three methodologies were employed, one to evaluate the effect of PA on lipid peroxidation in TBARS test and the other two to investigate its action as substance radical scavenging OH and NO. In all tests, the PA showed antioxidant activity, reducing by 70% the production of free radicals. As for histopathological evaluation, the PA did not cause significant tissue changes in both brain areas studied. Therefore, the results obtained in this study demonstrate that perillyl alcohol has an antinociceptive effect mediated by the opioid system and antioxidant mechanisms, without the direct participation of muscarinic systems, adenosinergic, dopaminergic, K+ATP channels and via L-arginine nitric oxide. The monoterpene also did not show significant neurotoxicity.O álcool perílico (p-mentha-1,8-diene-7-ol) é um membro da família dos monoterpenos encontrado em plantas dos gêneros Lavandula, Mentha, Cymbopogon, entre outros. É sabido que o álcool perílico (AP) possui atividade antinociceptiva, porém seu mecanismo de ação ainda permanece desconhecido. No presente trabalho foi investigado o possível mecanismo de ação do AP utilizando antagonistas farmacológicos e testes in vitro, e avaliada a neurotoxicidade histológica à nível do hipocampo e corpo estriado. O teste das contorções abdominais induzidas pelo ácido acético foi o protocolo de escolha para testar o monoterpeno na dose de 100 mg/kg frente aos antagonistas. Os resultados mostram uma reversão do efeito antinociceptivo do AP (AP 3,4 ± 1,7 contorções) após o pré-tratamento com a naloxona (NLX+AP 10,4 ± 2,3 contorções) indicando a participação do sistema opioide no seu mecanismo de ação. Diferentemente da naloxona, os antagonistas, muscarínico (atropina), adenosinérgico (cafeína), dopaminérgico (sulpirida), a L-arginina - L-NNA e a Glibenclamida, não foram capazes de reduzir o efeito do AP frente às contorções abdominais. Na avaliação da atividade antioxidante in vitro do AP, foram empregadas três metodologias, uma para avaliar o efeito do AP sobre a peroxidação lipídica, no teste de TBARS, e as outras duas para investigar sua ação como substância sequestradora de radicais livres OH e NO. Em todos os testes, o AP demonstrou atividade antioxidante, reduzindo em até 70% a produção de radicais livres. Quanto à avaliação histopatológica, o AP não provocou alterações teciduais significativas nas duas áreas cerebrais estudadas. Portanto, os resultados demonstram que o álcool perílico apresenta um efeito antinociceptivo mediado pelo sistema opioide e por mecanismos antioxidantes, sem a participação direta dos sistemas muscarínico, adenosinérgico, dopaminérgico, dos canais para K+ATP e da via L-arginina óxido nítrico. O monoterpeno também não apresentou neurotoxicidade significativa.Made available in DSpace on 2015-05-14T12:59:57Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1887110 bytes, checksum: fccf12022559bc9d652bf19f1b3be1dd (MD5) Previous issue date: 2013-09-27Made available in DSpace on 2018-07-21T00:25:07Z (GMT). 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dc.title.por.fl_str_mv Estudo do mecanismo de ação antinociceptivo e avaliação histopatológica cerebral do (S)-(-)-álcool perílico em camundongos
dc.title.alternative.eng.fl_str_mv Study of the mechanism of action antinociceptive and histopathological evaluation of the brain (s)-(-)-perillyl alcohol in mice
title Estudo do mecanismo de ação antinociceptivo e avaliação histopatológica cerebral do (S)-(-)-álcool perílico em camundongos
spellingShingle Estudo do mecanismo de ação antinociceptivo e avaliação histopatológica cerebral do (S)-(-)-álcool perílico em camundongos
Benedito, Rubens Batista
Álcool perílico
Atividade antinociceptiva
Opioide
Antioxidante
Avaliação histopatológica
Perillyl alcohol
Antinociceptive activity
Opioid
Antioxidant
Histopathological evaluation
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
title_short Estudo do mecanismo de ação antinociceptivo e avaliação histopatológica cerebral do (S)-(-)-álcool perílico em camundongos
title_full Estudo do mecanismo de ação antinociceptivo e avaliação histopatológica cerebral do (S)-(-)-álcool perílico em camundongos
title_fullStr Estudo do mecanismo de ação antinociceptivo e avaliação histopatológica cerebral do (S)-(-)-álcool perílico em camundongos
title_full_unstemmed Estudo do mecanismo de ação antinociceptivo e avaliação histopatológica cerebral do (S)-(-)-álcool perílico em camundongos
title_sort Estudo do mecanismo de ação antinociceptivo e avaliação histopatológica cerebral do (S)-(-)-álcool perílico em camundongos
author Benedito, Rubens Batista
author_facet Benedito, Rubens Batista
author_role author
dc.contributor.advisor1.fl_str_mv Almeida, Reinaldo Nobrega de
dc.contributor.advisor1ID.fl_str_mv CPF:08693463420
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/5034028656386134
dc.contributor.advisor-co1.fl_str_mv Sá, Rita de Cassia da Silveira e
dc.contributor.advisor-co1ID.fl_str_mv CPF:50317768620
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/9644294250708309
dc.contributor.authorID.fl_str_mv CPF:05775792408
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/3086818599920651
dc.contributor.author.fl_str_mv Benedito, Rubens Batista
contributor_str_mv Almeida, Reinaldo Nobrega de
Sá, Rita de Cassia da Silveira e
dc.subject.por.fl_str_mv Álcool perílico
Atividade antinociceptiva
Opioide
Antioxidante
Avaliação histopatológica
topic Álcool perílico
Atividade antinociceptiva
Opioide
Antioxidante
Avaliação histopatológica
Perillyl alcohol
Antinociceptive activity
Opioid
Antioxidant
Histopathological evaluation
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
dc.subject.eng.fl_str_mv Perillyl alcohol
Antinociceptive activity
Opioid
Antioxidant
Histopathological evaluation
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
description The perillyl alcohol (p-mentha-1,8-diene-7-ol) is a member of the family of monoterpenes found in plants of the genus Lavandula, Mentha, Cymbopogon, among others. It is known that perillyl alcohol (AP) has antinociceptive activity, but its mechanism of action remains unknown. In the present study was investigated the possible mechanism of action of PA using pharmacological antagonists and in vitro, and evaluated the histological level neurotoxicity in the hippocampus and striatum. The test of writhing induced by acetic acid was the protocol of choice for testing the monoterpene at a dose of 100 mg/kg against antagonists. The results show a reversal of the antinociceptive effect of PA (PA 3,4 ± 1,7 writhing) after pretreatment with naloxone (NLX+PA 10,4 ± 2,3 writhing) indicating the participation of the opioid system in its mechanism of action. Unlike naloxone, antagonists, muscarinic (atropine), adenosinergic (caffeine), dopamine (sulpiride), L-arginine - L-NNA and glibenclamide, were not able to reduce the effect of the PA front abdominal writhing. In the evaluation of in vitro antioxidant activity of the PA, three methodologies were employed, one to evaluate the effect of PA on lipid peroxidation in TBARS test and the other two to investigate its action as substance radical scavenging OH and NO. In all tests, the PA showed antioxidant activity, reducing by 70% the production of free radicals. As for histopathological evaluation, the PA did not cause significant tissue changes in both brain areas studied. Therefore, the results obtained in this study demonstrate that perillyl alcohol has an antinociceptive effect mediated by the opioid system and antioxidant mechanisms, without the direct participation of muscarinic systems, adenosinergic, dopaminergic, K+ATP channels and via L-arginine nitric oxide. The monoterpene also did not show significant neurotoxicity.
publishDate 2013
dc.date.issued.fl_str_mv 2013-09-27
dc.date.available.fl_str_mv 2014-09-10
2018-07-21T00:25:07Z
dc.date.accessioned.fl_str_mv 2015-05-14T12:59:57Z
2018-07-21T00:25:07Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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format doctoralThesis
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dc.identifier.citation.fl_str_mv BENEDITO, Rubens Batista. Study of the mechanism of action antinociceptive and histopathological evaluation of the brain (s)-(-)-perillyl alcohol in mice. 2013. 109 f. Tese (Doutorado em Farmacologia) - Universidade Federal da Paraí­ba, João Pessoa, 2013.
dc.identifier.uri.fl_str_mv https://repositorio.ufpb.br/jspui/handle/tede/6802
identifier_str_mv BENEDITO, Rubens Batista. Study of the mechanism of action antinociceptive and histopathological evaluation of the brain (s)-(-)-perillyl alcohol in mice. 2013. 109 f. Tese (Doutorado em Farmacologia) - Universidade Federal da Paraí­ba, João Pessoa, 2013.
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dc.publisher.initials.fl_str_mv UFPB
dc.publisher.country.fl_str_mv BR
dc.publisher.department.fl_str_mv Farmacologia
publisher.none.fl_str_mv Universidade Federal da Paraí­ba
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