Compostos voláteis como sedativos, anestésicos e antinociceptivos em peixes
Ano de defesa: | 2020 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
Centro de Ciências da Saúde |
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Farmacologia
|
Departamento: |
Farmacologia
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/24012 |
Resumo: | Natural products are a drug discovery source for both humans and veterinary treatment. Consequently, in the last decade, essential oils have been researched as fish anesthetics and sedatives, however, there are a small number of antinociceptive drug development studies using fish as an animal model. Also, the essential oils use is limited in pisciculture maybe due to the physicochemical limitations, such as high hydrophobicity. Thus, nanotechnology can protect and facilitate these compounds dispersion in water. Therefore, through this dissertation, it is expected to improve the volatile compounds use as anesthetic and sedative agents, even as increase the antinociceptive use as well-being promoters for fish. Firstly, silver catfish (Rhamdia quelen) nociceptive method was standardized with acetic acid 15 % (3μL), formalin 1 % (10 μL) and menthol 0.5 % (1 μL) administered in the lips. Additionally, due to the Nectandra grandiflora essential oil anesthetic/sedative activity, it was suggested to evaluate the antinociceptive activity, as well as linalool. In addition, we developed a N. grandiflora essential oil nanoemulsion formulation (NEN), and evaluate the anesthetic, sedative and toxicity by immersion bath in Nile tilapia (Oreochromis niloticus) compared with the free essential oil (FEO). Chemical analyses were performed by gas chromatography coupled to mass spectrometry and flame ionization detector. Among the results, to induce the nociceptive-like behavior in silver catfish we used 15 % acetic acid (3 μL), 1 % formalin (10 μL) and 0.5 % menthol (1 μL). Nociceptive-like behavior was verified in ten locomotor parameters that were reversed with intramuscular morphine (5 mg/kg) injection, and this antinociceptive activity was antagonized by naloxone (5 mg/kg). However, only acetic acid-induced the nociceptive-like behavior at the maximum speed parameter. Given this, the volatile compounds treatment was performed only against acetic acid and the N. grandiflora essential oil (10 mg/kg) had low activity. Linalool (50 mg/kg), on the other hand, has strong antinociceptive activity by reversing all locomotors parameters, with a related mechanism to opioid receptors. Secondarily, through the spontaneous emulsification process, we developed thirteen NEN and the nanoemulsification process protected the oil chemical composition for 60 days and reduced the FEO side effects. Therefore, the NEN 100 mg/L concentration for anesthetic and 30 mg/L for sedation application are safe. Thus, FEO depressant activity was improved and also refined for tilapia. Moreover, the two fish species use covers not only nociceptive-like behavior in an unknown species but also a new O. niloticus pharmacological alternative for sedation and anesthesia. Consequently, the silver catfish new nociception experimental model proposed demonstrated specificity, since the nociceptive-like behavior was reverted by linalool and morphine, which have described analgesic activity. Briefly, this dissertation contributes to research that aims to combine volatile compound and nanotechnological knowledge into an effective and safe anesthetic drug development. |
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2022-04-04T14:28:20Z2022-04-04T14:28:20Z2020-02-18http://repositorio.ufsm.br/handle/1/24012Natural products are a drug discovery source for both humans and veterinary treatment. Consequently, in the last decade, essential oils have been researched as fish anesthetics and sedatives, however, there are a small number of antinociceptive drug development studies using fish as an animal model. Also, the essential oils use is limited in pisciculture maybe due to the physicochemical limitations, such as high hydrophobicity. Thus, nanotechnology can protect and facilitate these compounds dispersion in water. Therefore, through this dissertation, it is expected to improve the volatile compounds use as anesthetic and sedative agents, even as increase the antinociceptive use as well-being promoters for fish. Firstly, silver catfish (Rhamdia quelen) nociceptive method was standardized with acetic acid 15 % (3μL), formalin 1 % (10 μL) and menthol 0.5 % (1 μL) administered in the lips. Additionally, due to the Nectandra grandiflora essential oil anesthetic/sedative activity, it was suggested to evaluate the antinociceptive activity, as well as linalool. In addition, we developed a N. grandiflora essential oil nanoemulsion formulation (NEN), and evaluate the anesthetic, sedative and toxicity by immersion bath in Nile tilapia (Oreochromis niloticus) compared with the free essential oil (FEO). Chemical analyses were performed by gas chromatography coupled to mass spectrometry and flame ionization detector. Among the results, to induce the nociceptive-like behavior in silver catfish we used 15 % acetic acid (3 μL), 1 % formalin (10 μL) and 0.5 % menthol (1 μL). Nociceptive-like behavior was verified in ten locomotor parameters that were reversed with intramuscular morphine (5 mg/kg) injection, and this antinociceptive activity was antagonized by naloxone (5 mg/kg). However, only acetic acid-induced the nociceptive-like behavior at the maximum speed parameter. Given this, the volatile compounds treatment was performed only against acetic acid and the N. grandiflora essential oil (10 mg/kg) had low activity. Linalool (50 mg/kg), on the other hand, has strong antinociceptive activity by reversing all locomotors parameters, with a related mechanism to opioid receptors. Secondarily, through the spontaneous emulsification process, we developed thirteen NEN and the nanoemulsification process protected the oil chemical composition for 60 days and reduced the FEO side effects. Therefore, the NEN 100 mg/L concentration for anesthetic and 30 mg/L for sedation application are safe. Thus, FEO depressant activity was improved and also refined for tilapia. Moreover, the two fish species use covers not only nociceptive-like behavior in an unknown species but also a new O. niloticus pharmacological alternative for sedation and anesthesia. Consequently, the silver catfish new nociception experimental model proposed demonstrated specificity, since the nociceptive-like behavior was reverted by linalool and morphine, which have described analgesic activity. Briefly, this dissertation contributes to research that aims to combine volatile compound and nanotechnological knowledge into an effective and safe anesthetic drug development.Produtos naturais representam uma fonte de novos medicamentos, na última década, óleos essenciais vêm sendo investigados como anestésicos e sedativos para peixes. Entretanto o desenvolvimento de antinociceptivos é pouco estudado, assim como a utilização de peixes como modelo animal. Ainda, os óleos essenciais são pouco utilizados na prática como anestésicos para peixes e isso pode estar ligado às suas limitações físico-químicas. Neste sentido, a nanotecnologia pode ser utilizada para proteger e facilitar a dispersão em água destes compostos. Logo, objetivamos aprimorar o uso de compostos voláteis como agentes anestésicos e sedativos e antinociceptivos como promotores de bem-estar em peixes. Para isso, padronizamos um método nociceptivo com o jundiá (Rhamdia quelen) com três diferentes algógenos, ácido acético 15 % (3μL), formalina 1 % (10 μL) e mentol 0,5 % (1 μL). Adicionalmente, devido a atividade anestésica/sedativa do óleo essencial de Nectandra grandiflora, foi proposta a avaliação da atividade antinociceptiva, assim como do linalol. Além disso, desenvolvemos uma formulação de nanoemulsão com este óleo essencial e avaliação da atividade anestésica e sedativa por banho de imersão, assim como sua toxicidade em tilápia do Nilo (Oreochromis niloticus). As análises químicas foram realizadas por cromatógrafo gasoso acoplado a espectrometria de massas e detector de ionização em chama. O comportamento tipo-nociceptivo do jundiá foi verificado em dez parâmetros locomotores e revertido com morfina (5 mg/kg) e antagonizado pelo pré-tratamento com naloxona (5 mg/kg). Entretanto, apenas o ácido acético induziu o comportamento tipo-nociceptivo no parâmetro de velocidade máxima. Diante disto, realizamos o tratamento dos peixes com os compostos voláteis apenas frente a ao ácido como algógeno e verificamos a fraca atividade do óleo essencial (10 mg/kg). O linalol (50 mg/kg) apresentou forte atividade antinociceptiva ao reverter todos os parâmetros de atividade locomotora, com mecanismo da atividade ligado aos receptores opioides. Em um segundo momento, através do processo de emulsificação espontânea desenvolvemos uma formulação com o óleo essencial de N. grandiflora que protegeu e diminuiu os efeitos adversos, sendo seguras a concentração de 100 mg/L como anestésico e 30 mg/L para sedação de tilápias. A utilização de duas espécies de peixes abrange não só o comportamento tipo-nocioceptivo outrora desconhecido em Rhamdia quelen, mas também uma nova alternativa farmacológica para sedação e anestesia de O. niloticus. Desta forma, o novo modelo experimental proposto para nocicepção com jundiá demonstrou especificidade, já que foi possível observar a reversão do comportamento tipo-nociceptivo para o linalol e a morfina, que possuem atividade analgésica descrita. Em suma esta dissertação colabora para pesquisas que visam aliar o conhecimento nanotecnológico com compostos voláteis no desenvolvimento de medicamentos anestésicos mais eficazes e com menores efeitos adversos.porUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em FarmacologiaUFSMBrasilFarmacologiaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessRhamdia quelenOreochromis niloticusÓleo essencialNanoemulsãoNectandra grandifloraLinalolEssential oilNanoemulsionLinaloolCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIACompostos voláteis como sedativos, anestésicos e antinociceptivos em peixesVolatile compounds as sedative, anesthetic and antinocioceptive in fishinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisHeinzmann, Berta Mariahttp://lattes.cnpq.br/0786124562427815Baldisserotto, BernardoOurique, Aline FerreiraBarcellos, Leonardo Jose Gilhttp://lattes.cnpq.br/3892021490619118Rodrigues, Patricia201000000000600600600600600600ef52d431-0698-40fb-ab56-1dbd415cc5d7aa6a7661-a2ff-4a44-8bdd-7d40a2c76e859b760330-616c-4671-9767-37cb80c89437dd172234-8fdf-4467-8031-137b919d3f990494f003-7669-46b5-b83d-f26f6f885fefreponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGFARMACOLOGIA_2020_RODRIGUES_PATRICIA.pdfDIS_PPGFARMACOLOGIA_2020_RODRIGUES_PATRICIA.pdfDissertaçãoapplication/pdf7704262http://repositorio.ufsm.br/bitstream/1/24012/1/DIS_PPGFARMACOLOGIA_2020_RODRIGUES_PATRICIA.pdfd44beae9e1d2345aa1e2de535b2aa2fbMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81956http://repositorio.ufsm.br/bitstream/1/24012/3/license.txt2f0571ecee68693bd5cd3f17c1e075dfMD53CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8805http://repositorio.ufsm.br/bitstream/1/24012/2/license_rdf4460e5956bc1d1639be9ae6146a50347MD521/240122022-04-04 11:28:20.826oai:repositorio.ufsm.br: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 Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-04-04T14:28:20Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Compostos voláteis como sedativos, anestésicos e antinociceptivos em peixes |
dc.title.alternative.eng.fl_str_mv |
Volatile compounds as sedative, anesthetic and antinocioceptive in fish |
title |
Compostos voláteis como sedativos, anestésicos e antinociceptivos em peixes |
spellingShingle |
Compostos voláteis como sedativos, anestésicos e antinociceptivos em peixes Rodrigues, Patricia Rhamdia quelen Oreochromis niloticus Óleo essencial Nanoemulsão Nectandra grandiflora Linalol Essential oil Nanoemulsion Linalool CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Compostos voláteis como sedativos, anestésicos e antinociceptivos em peixes |
title_full |
Compostos voláteis como sedativos, anestésicos e antinociceptivos em peixes |
title_fullStr |
Compostos voláteis como sedativos, anestésicos e antinociceptivos em peixes |
title_full_unstemmed |
Compostos voláteis como sedativos, anestésicos e antinociceptivos em peixes |
title_sort |
Compostos voláteis como sedativos, anestésicos e antinociceptivos em peixes |
author |
Rodrigues, Patricia |
author_facet |
Rodrigues, Patricia |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Heinzmann, Berta Maria |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/0786124562427815 |
dc.contributor.advisor-co1.fl_str_mv |
Baldisserotto, Bernardo |
dc.contributor.referee1.fl_str_mv |
Ourique, Aline Ferreira |
dc.contributor.referee2.fl_str_mv |
Barcellos, Leonardo Jose Gil |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/3892021490619118 |
dc.contributor.author.fl_str_mv |
Rodrigues, Patricia |
contributor_str_mv |
Heinzmann, Berta Maria Baldisserotto, Bernardo Ourique, Aline Ferreira Barcellos, Leonardo Jose Gil |
dc.subject.por.fl_str_mv |
Rhamdia quelen Oreochromis niloticus Óleo essencial Nanoemulsão Nectandra grandiflora Linalol |
topic |
Rhamdia quelen Oreochromis niloticus Óleo essencial Nanoemulsão Nectandra grandiflora Linalol Essential oil Nanoemulsion Linalool CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
dc.subject.eng.fl_str_mv |
Essential oil Nanoemulsion Linalool |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Natural products are a drug discovery source for both humans and veterinary treatment. Consequently, in the last decade, essential oils have been researched as fish anesthetics and sedatives, however, there are a small number of antinociceptive drug development studies using fish as an animal model. Also, the essential oils use is limited in pisciculture maybe due to the physicochemical limitations, such as high hydrophobicity. Thus, nanotechnology can protect and facilitate these compounds dispersion in water. Therefore, through this dissertation, it is expected to improve the volatile compounds use as anesthetic and sedative agents, even as increase the antinociceptive use as well-being promoters for fish. Firstly, silver catfish (Rhamdia quelen) nociceptive method was standardized with acetic acid 15 % (3μL), formalin 1 % (10 μL) and menthol 0.5 % (1 μL) administered in the lips. Additionally, due to the Nectandra grandiflora essential oil anesthetic/sedative activity, it was suggested to evaluate the antinociceptive activity, as well as linalool. In addition, we developed a N. grandiflora essential oil nanoemulsion formulation (NEN), and evaluate the anesthetic, sedative and toxicity by immersion bath in Nile tilapia (Oreochromis niloticus) compared with the free essential oil (FEO). Chemical analyses were performed by gas chromatography coupled to mass spectrometry and flame ionization detector. Among the results, to induce the nociceptive-like behavior in silver catfish we used 15 % acetic acid (3 μL), 1 % formalin (10 μL) and 0.5 % menthol (1 μL). Nociceptive-like behavior was verified in ten locomotor parameters that were reversed with intramuscular morphine (5 mg/kg) injection, and this antinociceptive activity was antagonized by naloxone (5 mg/kg). However, only acetic acid-induced the nociceptive-like behavior at the maximum speed parameter. Given this, the volatile compounds treatment was performed only against acetic acid and the N. grandiflora essential oil (10 mg/kg) had low activity. Linalool (50 mg/kg), on the other hand, has strong antinociceptive activity by reversing all locomotors parameters, with a related mechanism to opioid receptors. Secondarily, through the spontaneous emulsification process, we developed thirteen NEN and the nanoemulsification process protected the oil chemical composition for 60 days and reduced the FEO side effects. Therefore, the NEN 100 mg/L concentration for anesthetic and 30 mg/L for sedation application are safe. Thus, FEO depressant activity was improved and also refined for tilapia. Moreover, the two fish species use covers not only nociceptive-like behavior in an unknown species but also a new O. niloticus pharmacological alternative for sedation and anesthesia. Consequently, the silver catfish new nociception experimental model proposed demonstrated specificity, since the nociceptive-like behavior was reverted by linalool and morphine, which have described analgesic activity. Briefly, this dissertation contributes to research that aims to combine volatile compound and nanotechnological knowledge into an effective and safe anesthetic drug development. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020-02-18 |
dc.date.accessioned.fl_str_mv |
2022-04-04T14:28:20Z |
dc.date.available.fl_str_mv |
2022-04-04T14:28:20Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/24012 |
url |
http://repositorio.ufsm.br/handle/1/24012 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
201000000000 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 600 600 |
dc.relation.authority.fl_str_mv |
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dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Farmacologia |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Farmacologia |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
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