Toxicidade do cloridrato de tramadol e da cicuta douglasii no sistema nervoso central em modelos experimentais

Detalhes bibliográficos
Autor(a) principal: Orlando, Camila França de Paula
Data de Publicação: 2015
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da UFG
dARK ID: ark:/38995/001300000bdv3
Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/5697
Resumo: This thesis presents two different studies about neurotoxicity in laboratory animals. The first study was about a sintetic analgesic called tramadol hydrochloride. The second study is about an natural poison plant called Cicuta douglasii. Tramadol is considered a safe drug as compared to other opioids. However, it has been suggested that spinal administration may trigger neurotoxicity. The objective of this study was to evaluate the neurotoxic effects of tramadol administered by spinal injection in rabbits. Thirty-two rabbits were randomly divided into two groups of 16 animals, with a control group (CG) and a tramadol group (TG). Each group was divided into four subgroups according to the application site (epidural and intrathecal) and evaluation time (seven and 30 days). For administration of tramadol or saline into the epidural or intrathecal space, a polyethylene catheter was implanted between the sixth and seventh lumbar spinous process where it remained for seven consecutive days in all animals. Various clinical and histology evaluations were conducted including determining the treatment effects on the frequency and severity of vacuolization, gliosis, inflammatory infiltrate, heart attacks, bleeding, chromatolysis, cellular edema, Wallerian degeneration, and malacia. Significant differences were found between groups for the Wallerian degeneration. Wallerian degeneration was more frequent in TG than in the CG. We conclude that tramadol can worsen nerve fiber lesions, as shown by Wallerian degeneration caused by catheterization of the epidural and intrathecal space in rabbits. Water hemlock are plants of the genus Cicuta and are toxic to animals and humans. The primary toxin is, cicutoxin, which is present in large concentrations in the tubers; other parts of the plant are toxic, but may contain lower concentrations of cicutoxin. Further, other forms of cicutoxin such as cicutols may contribute to toxicity in various plant parts. The objective of this study was to determine the toxicity of different parts of Cicuta douglasii and characterize their behavioral effects in mice. An aqueous extract was made of green seeds, dry seeds, tubers, flowers and stems of Cicuta douglasii and dosed orally to mice to determine the LD50 (the up and down test). The results indicated that only the green seeds and tubers were toxic to animals by inducing clonic-tonic seizures and death. The LD50 was 17mg/kg and 1320mg/kg for tubers and green seed, respectively. Several tests were used to evaluate motor function and behavior in treated vs. control mice including Grip Strength, Rotarod, Tremor Monitor and Open Field. For each test 12 animals were used per group. The control group (CG) received saline orally, one group received 40% of the LD50 orally (G40) and another group received 85% of the LD50 (G85). The animals were evaluated before gavage and 30 min, 90 min, 120 min, 150 min, 180 min, 240 min and 300 min after gavage. In summary, Cicuta douglasii affected muscle function of mice, including their ability to grasp and hold onto objects, their balance and motility on a Rotarod, motor activity, and exploratory and anxiety-related (i.e., thigmotaxis) behaviors. Seizures interspersed with CNS depression were observed in animals poisoned by Cicuta douglasii.
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spelling Damasceno, Adilson Donizetihttp://lattes.cnpq.br/3900110295277130Moreno, Juan Carlos Duquehttp://lattes.cnpq.br/8509640024284103Silva, Luiz Antônio Franco dahttp://lattes.cnpq.br/0446055905975647Damasceno, Adilson DonizetiLima, Flávia Gontijo deMiguel, Marina PachechoCunha, Paulo Henrique Jorge daMoura, Veridiana Maria Brianezi Dignani dehttp://lattes.cnpq.br/4298822093847635Orlando, Camila França de Paula2016-06-28T13:10:17Z2015-12-21ORLANDO, C. F. P. Toxicidade do cloridrato de tramadol e da cicuta douglasii no sistema nervoso central em modelos experimentais. 2015. 71 f. Tese (Doutordado em Ciência Animal) - Universidade Federal de Goiás, Goiânia, 2015.http://repositorio.bc.ufg.br/tede/handle/tede/5697ark:/38995/001300000bdv3This thesis presents two different studies about neurotoxicity in laboratory animals. The first study was about a sintetic analgesic called tramadol hydrochloride. The second study is about an natural poison plant called Cicuta douglasii. Tramadol is considered a safe drug as compared to other opioids. However, it has been suggested that spinal administration may trigger neurotoxicity. The objective of this study was to evaluate the neurotoxic effects of tramadol administered by spinal injection in rabbits. Thirty-two rabbits were randomly divided into two groups of 16 animals, with a control group (CG) and a tramadol group (TG). Each group was divided into four subgroups according to the application site (epidural and intrathecal) and evaluation time (seven and 30 days). For administration of tramadol or saline into the epidural or intrathecal space, a polyethylene catheter was implanted between the sixth and seventh lumbar spinous process where it remained for seven consecutive days in all animals. Various clinical and histology evaluations were conducted including determining the treatment effects on the frequency and severity of vacuolization, gliosis, inflammatory infiltrate, heart attacks, bleeding, chromatolysis, cellular edema, Wallerian degeneration, and malacia. Significant differences were found between groups for the Wallerian degeneration. Wallerian degeneration was more frequent in TG than in the CG. We conclude that tramadol can worsen nerve fiber lesions, as shown by Wallerian degeneration caused by catheterization of the epidural and intrathecal space in rabbits. Water hemlock are plants of the genus Cicuta and are toxic to animals and humans. The primary toxin is, cicutoxin, which is present in large concentrations in the tubers; other parts of the plant are toxic, but may contain lower concentrations of cicutoxin. Further, other forms of cicutoxin such as cicutols may contribute to toxicity in various plant parts. The objective of this study was to determine the toxicity of different parts of Cicuta douglasii and characterize their behavioral effects in mice. An aqueous extract was made of green seeds, dry seeds, tubers, flowers and stems of Cicuta douglasii and dosed orally to mice to determine the LD50 (the up and down test). The results indicated that only the green seeds and tubers were toxic to animals by inducing clonic-tonic seizures and death. The LD50 was 17mg/kg and 1320mg/kg for tubers and green seed, respectively. Several tests were used to evaluate motor function and behavior in treated vs. control mice including Grip Strength, Rotarod, Tremor Monitor and Open Field. For each test 12 animals were used per group. The control group (CG) received saline orally, one group received 40% of the LD50 orally (G40) and another group received 85% of the LD50 (G85). The animals were evaluated before gavage and 30 min, 90 min, 120 min, 150 min, 180 min, 240 min and 300 min after gavage. In summary, Cicuta douglasii affected muscle function of mice, including their ability to grasp and hold onto objects, their balance and motility on a Rotarod, motor activity, and exploratory and anxiety-related (i.e., thigmotaxis) behaviors. Seizures interspersed with CNS depression were observed in animals poisoned by Cicuta douglasii.Esta tese apresentou dois distintos estudos sobre neurotoxicidade em animais de laboratório. O primeiro estudo envolveu um analgésico sintético denominado cloridrato de tramadol. O segundo estudo envolveu uma planta tóxica denominada Cicuta douglasii e também conhecida como Water Hemlock. O tramadol é considerado um fármaco seguro se comparado aos outros opioides. No entanto, foi sugerido que se administrado por via espinhal pode desencadear sinais de neurotoxicidade. Baseando-se nesta afirmativa foi proposto com este estudo avaliar os efeitos neurotóxicos do tramadol aplicado por via espinhal em coelhos. Foram utilizados para o estudo 32 coelhos aleatoriamente divididos em dois grupos de 16 animais, grupo controle (GC) e grupo tramadol (GT). Cada grupo foi subdividido em mais quatro subgrupos de acordo com o local de aplicação (epidural e intratecal) e o tempo de avaliação (sete e 30 dias). Para administração do tramadol ou da solução salina nos espaços epidural ou intratecal foi realizado a implantação de um cateter de polietileno entre o sexto e o sétimo processo espinhoso lombar onde permaneceu durante sete dias consecutivos em todos os animais. Para avaliação histológica, as variáveis analisadas foram presença de vacuolização, gliose, infiltrado inflamatório, infarto, hemorragia, cromatólise, edema celular, degeneração walleriana e malácia. Foram encontradas diferenças significativas entre os grupos na variável degeneração walleriana, no qual se verificou uma maior frequência no GT que no GC. Conclui-se que o tramadol pode agravar as lesões, representadas por degeneração walleriana, provocadas pela cateterização crônica do espaço epidural e intratecal em coelhos. As water hemlocks são plantas do gênero Cicuta e consideradas tóxicas para animais e humanos. Sua principal toxina conhecida, a cicutoxina, está presente em grandes concentrações no tubérculo da planta, contudo, estudos mais recentes têm sugerido que outras partes da planta são tóxicas. Face ao exposto, este estudo teve como finalidade determinar a toxicidade de diferentes partes da Cicuta douglasii e caracterizar seus efeitos comportamentais em camundongos. Foi utilizado um extrato aquoso de sementes verdes, sementes secas, tubérculos, flores e caules de Cicuta douglasii e administrado via oral em camundongos para determinação da DL50 (teste de up and down). Os resultados indicaram que apenas o tubérculo e as sementes verdes são tóxicos para os animais induzindo convulsões tônico-clônicas e morte e as respectivas DL50 foram 17mg/kg e 1320 mg/kg. Para os testes de função motora e de comportamento foram utilizados o GripStrenght, Rota Rod, Tremor Monitor e Campo Aberto. A dose utilizada para os testes foi 40% (10 ml/kg) e 85% (20 ml/kg) da DL50. Para cada teste foram utilizados 12 animais por grupo. O grupo controle (GC) recebeu solução salina por via oral, um grupo recebeu 40% da DL50 por via oral (G40) e outro grupo recebeu 85% da DL50 (G85). Os animais foram avaliados antes da gavagem e 30min, 90 min, 120 min, 150 min, 180 min, 240 min e 300 min após a gavagem. De modo geral, pode-se concluir que a Cicuta douglasii afetou a função muscular de camundongos, a habilidade de preensão dos animais a objetos, a coordenação motora, a atividade motora e o comportamento. Crises convulsivas intercaladas com depressão do SNC foram observadas nos animais intoxicados pela Cicuta douglasiiSubmitted by Cássia Santos (cassia.bcufg@gmail.com) on 2016-06-16T11:54:04Z No. of bitstreams: 2 Tese - Camila Franca de Paula Orlando - 2015.pdf: 2619656 bytes, checksum: cb74bf2b84fcf86e2eb757ba7b9413a2 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-06-28T13:10:17Z (GMT) No. of bitstreams: 2 Tese - Camila Franca de Paula Orlando - 2015.pdf: 2619656 bytes, checksum: cb74bf2b84fcf86e2eb757ba7b9413a2 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Made available in DSpace on 2016-06-28T13:10:17Z (GMT). No. of bitstreams: 2 Tese - Camila Franca de Paula Orlando - 2015.pdf: 2619656 bytes, checksum: cb74bf2b84fcf86e2eb757ba7b9413a2 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2015-12-21Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESConselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqapplication/pdfporUniversidade Federal de GoiásPrograma de Pós-graduação em Ciência Animal (EVZ)UFGBrasilEscola de Veterinária e Zootecnia - EVZ (RG)http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessDegeneração WallerianaNeurotoxicidadeOpioideCicutoxinaNeurotoxicityOpioidCicutoxinWallerian degenerationPATOLOGIA ANIMAL::PATOLOGIA CLINICA ANIMALToxicidade do cloridrato de tramadol e da cicuta douglasii no sistema nervoso central em modelos experimentaisToxicity of hydrochloride tramadol and Cicuta douglasii in the central nervous system in experimental modelsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis4581960685150189167600600600600600-62175521142490945826109832347911310612075167498588264571-2555911436985713659reponame:Repositório Institucional da UFGinstname:Universidade Federal de Goiás (UFG)instacron:UFGLICENSElicense.txtlicense.txttext/plain; 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dc.title.por.fl_str_mv Toxicidade do cloridrato de tramadol e da cicuta douglasii no sistema nervoso central em modelos experimentais
dc.title.alternative.eng.fl_str_mv Toxicity of hydrochloride tramadol and Cicuta douglasii in the central nervous system in experimental models
title Toxicidade do cloridrato de tramadol e da cicuta douglasii no sistema nervoso central em modelos experimentais
spellingShingle Toxicidade do cloridrato de tramadol e da cicuta douglasii no sistema nervoso central em modelos experimentais
Orlando, Camila França de Paula
Degeneração Walleriana
Neurotoxicidade
Opioide
Cicutoxina
Neurotoxicity
Opioid
Cicutoxin
Wallerian degeneration
PATOLOGIA ANIMAL::PATOLOGIA CLINICA ANIMAL
title_short Toxicidade do cloridrato de tramadol e da cicuta douglasii no sistema nervoso central em modelos experimentais
title_full Toxicidade do cloridrato de tramadol e da cicuta douglasii no sistema nervoso central em modelos experimentais
title_fullStr Toxicidade do cloridrato de tramadol e da cicuta douglasii no sistema nervoso central em modelos experimentais
title_full_unstemmed Toxicidade do cloridrato de tramadol e da cicuta douglasii no sistema nervoso central em modelos experimentais
title_sort Toxicidade do cloridrato de tramadol e da cicuta douglasii no sistema nervoso central em modelos experimentais
author Orlando, Camila França de Paula
author_facet Orlando, Camila França de Paula
author_role author
dc.contributor.advisor1.fl_str_mv Damasceno, Adilson Donizeti
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/3900110295277130
dc.contributor.advisor-co1.fl_str_mv Moreno, Juan Carlos Duque
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/8509640024284103
dc.contributor.advisor-co2.fl_str_mv Silva, Luiz Antônio Franco da
dc.contributor.advisor-co2Lattes.fl_str_mv http://lattes.cnpq.br/0446055905975647
dc.contributor.referee1.fl_str_mv Damasceno, Adilson Donizeti
dc.contributor.referee2.fl_str_mv Lima, Flávia Gontijo de
dc.contributor.referee3.fl_str_mv Miguel, Marina Pachecho
dc.contributor.referee4.fl_str_mv Cunha, Paulo Henrique Jorge da
dc.contributor.referee5.fl_str_mv Moura, Veridiana Maria Brianezi Dignani de
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/4298822093847635
dc.contributor.author.fl_str_mv Orlando, Camila França de Paula
contributor_str_mv Damasceno, Adilson Donizeti
Moreno, Juan Carlos Duque
Silva, Luiz Antônio Franco da
Damasceno, Adilson Donizeti
Lima, Flávia Gontijo de
Miguel, Marina Pachecho
Cunha, Paulo Henrique Jorge da
Moura, Veridiana Maria Brianezi Dignani de
dc.subject.por.fl_str_mv Degeneração Walleriana
Neurotoxicidade
Opioide
Cicutoxina
topic Degeneração Walleriana
Neurotoxicidade
Opioide
Cicutoxina
Neurotoxicity
Opioid
Cicutoxin
Wallerian degeneration
PATOLOGIA ANIMAL::PATOLOGIA CLINICA ANIMAL
dc.subject.eng.fl_str_mv Neurotoxicity
Opioid
Cicutoxin
Wallerian degeneration
dc.subject.cnpq.fl_str_mv PATOLOGIA ANIMAL::PATOLOGIA CLINICA ANIMAL
description This thesis presents two different studies about neurotoxicity in laboratory animals. The first study was about a sintetic analgesic called tramadol hydrochloride. The second study is about an natural poison plant called Cicuta douglasii. Tramadol is considered a safe drug as compared to other opioids. However, it has been suggested that spinal administration may trigger neurotoxicity. The objective of this study was to evaluate the neurotoxic effects of tramadol administered by spinal injection in rabbits. Thirty-two rabbits were randomly divided into two groups of 16 animals, with a control group (CG) and a tramadol group (TG). Each group was divided into four subgroups according to the application site (epidural and intrathecal) and evaluation time (seven and 30 days). For administration of tramadol or saline into the epidural or intrathecal space, a polyethylene catheter was implanted between the sixth and seventh lumbar spinous process where it remained for seven consecutive days in all animals. Various clinical and histology evaluations were conducted including determining the treatment effects on the frequency and severity of vacuolization, gliosis, inflammatory infiltrate, heart attacks, bleeding, chromatolysis, cellular edema, Wallerian degeneration, and malacia. Significant differences were found between groups for the Wallerian degeneration. Wallerian degeneration was more frequent in TG than in the CG. We conclude that tramadol can worsen nerve fiber lesions, as shown by Wallerian degeneration caused by catheterization of the epidural and intrathecal space in rabbits. Water hemlock are plants of the genus Cicuta and are toxic to animals and humans. The primary toxin is, cicutoxin, which is present in large concentrations in the tubers; other parts of the plant are toxic, but may contain lower concentrations of cicutoxin. Further, other forms of cicutoxin such as cicutols may contribute to toxicity in various plant parts. The objective of this study was to determine the toxicity of different parts of Cicuta douglasii and characterize their behavioral effects in mice. An aqueous extract was made of green seeds, dry seeds, tubers, flowers and stems of Cicuta douglasii and dosed orally to mice to determine the LD50 (the up and down test). The results indicated that only the green seeds and tubers were toxic to animals by inducing clonic-tonic seizures and death. The LD50 was 17mg/kg and 1320mg/kg for tubers and green seed, respectively. Several tests were used to evaluate motor function and behavior in treated vs. control mice including Grip Strength, Rotarod, Tremor Monitor and Open Field. For each test 12 animals were used per group. The control group (CG) received saline orally, one group received 40% of the LD50 orally (G40) and another group received 85% of the LD50 (G85). The animals were evaluated before gavage and 30 min, 90 min, 120 min, 150 min, 180 min, 240 min and 300 min after gavage. In summary, Cicuta douglasii affected muscle function of mice, including their ability to grasp and hold onto objects, their balance and motility on a Rotarod, motor activity, and exploratory and anxiety-related (i.e., thigmotaxis) behaviors. Seizures interspersed with CNS depression were observed in animals poisoned by Cicuta douglasii.
publishDate 2015
dc.date.issued.fl_str_mv 2015-12-21
dc.date.accessioned.fl_str_mv 2016-06-28T13:10:17Z
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dc.identifier.citation.fl_str_mv ORLANDO, C. F. P. Toxicidade do cloridrato de tramadol e da cicuta douglasii no sistema nervoso central em modelos experimentais. 2015. 71 f. Tese (Doutordado em Ciência Animal) - Universidade Federal de Goiás, Goiânia, 2015.
dc.identifier.uri.fl_str_mv http://repositorio.bc.ufg.br/tede/handle/tede/5697
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identifier_str_mv ORLANDO, C. F. P. Toxicidade do cloridrato de tramadol e da cicuta douglasii no sistema nervoso central em modelos experimentais. 2015. 71 f. Tese (Doutordado em Ciência Animal) - Universidade Federal de Goiás, Goiânia, 2015.
ark:/38995/001300000bdv3
url http://repositorio.bc.ufg.br/tede/handle/tede/5697
dc.language.iso.fl_str_mv por
language por
dc.relation.program.fl_str_mv 4581960685150189167
dc.relation.confidence.fl_str_mv 600
600
600
600
600
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dc.relation.cnpq.fl_str_mv 610983234791131061
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dc.publisher.none.fl_str_mv Universidade Federal de Goiás
dc.publisher.program.fl_str_mv Programa de Pós-graduação em Ciência Animal (EVZ)
dc.publisher.initials.fl_str_mv UFG
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Escola de Veterinária e Zootecnia - EVZ (RG)
publisher.none.fl_str_mv Universidade Federal de Goiás
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