Compostos voláteis como sedativos, anestésicos e antinociceptivos em peixes

Detalhes bibliográficos
Ano de defesa: 2020
Autor(a) principal: Rodrigues, Patricia lattes
Orientador(a): Heinzmann, Berta Maria lattes
Banca de defesa: Ourique, Aline Ferreira, Barcellos, Leonardo Jose Gil
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.
id UFSM_ef1b86cc58f1fae10f8c965eaad3588b
oai_identifier_str oai:repositorio.ufsm.br:1/24012
network_acronym_str UFSM
network_name_str Biblioteca Digital de Teses e Dissertações do UFSM
repository_id_str
spelling 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 ef52d431-0698-40fb-ab56-1dbd415cc5d7
aa6a7661-a2ff-4a44-8bdd-7d40a2c76e85
9b760330-616c-4671-9767-37cb80c89437
dd172234-8fdf-4467-8031-137b919d3f99
0494f003-7669-46b5-b83d-f26f6f885fef
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 reponame:Biblioteca Digital de Teses e Dissertações do UFSM
instname:Universidade Federal de Santa Maria (UFSM)
instacron:UFSM
instname_str Universidade Federal de Santa Maria (UFSM)
instacron_str UFSM
institution UFSM
reponame_str Biblioteca Digital de Teses e Dissertações do UFSM
collection Biblioteca Digital de Teses e Dissertações do UFSM
bitstream.url.fl_str_mv http://repositorio.ufsm.br/bitstream/1/24012/1/DIS_PPGFARMACOLOGIA_2020_RODRIGUES_PATRICIA.pdf
http://repositorio.ufsm.br/bitstream/1/24012/3/license.txt
http://repositorio.ufsm.br/bitstream/1/24012/2/license_rdf
bitstream.checksum.fl_str_mv d44beae9e1d2345aa1e2de535b2aa2fb
2f0571ecee68693bd5cd3f17c1e075df
4460e5956bc1d1639be9ae6146a50347
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)
repository.mail.fl_str_mv atendimento.sib@ufsm.br||tedebc@gmail.com
_version_ 1793240131672473600