Farmacocinética de S-(+)-linalol em jundiás (Rhamdia quelen)
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional Manancial UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/24293 |
Resumo: | S-(+)-linalool is found in essential oils of aromatic plants as Lippia alba. This phytochemical had its sedative/anesthetic activity elucidated in Rhamdia quelen, popularly known as silver catfish. Thus, S-(+)-linalool has become an option as an anesthetic for aquaculture, but its pharmacokinetic profile was unknown until the development of this thesis. Therefore, the objective of this research was to determine the pharmacokinetic profile of S-(+)-linalool in silver catfish. S-(+)-linalool was quantified in plasma, tissue and water (from recovery) samples using gas chromatography with flame ionization detector (GC-FID). For blood and tissue collection, fish (n = 6, for each collection time) were exposed to an immersion bath with S-(+)-linalool (153 mg/L or 180 μL/L) for a maximum of 30 min (0.5 h) and after were transferred to aquariums without the anesthetic. The blood and brain samples were collected at different times in an interval from 0 to 4 hours and the other tissues (kidney, liver, gills and muscle) were collected in the interval from 0 to 24 hours (from the beginning of exposure to the anesthetic). To determine S-(+)-linalool excretion in the water another fish group (n = 6) was anesthetized as previously described and transferred to individual aquariums for up to 48 h. Water samples were collected during this period and later analyzed by GC-FID. The results found indicated that S-(+)-linalool is rapidly absorbed and distributed to the main tissues. The maximum concentrations (Cmax, tissues μg/g and plasma μg/mL) occurred in the magnitude: kidneyplasmabrainlivergillsmuscle (143.15, 129.33, 113.92, 110.03, 54.49 and 20.76, respectively) in 0.5 h (Tmax) with the exception of the brain (0.33 h). The S-(+)-linalool elimination occurs more quickly in the plasma, followed by the liver, kidneys, gills, muscle and brain (T1/2β: 1.36, 3.45, 6.30, 9.96, 11.04 and 57.27 h, respectively). Despite the slow elimination in the brain, all animals recovered from anesthesia within 10 min. Muscle was the second tissue with the highest T 1/2β, however the residual concentrations after 12 hours of clearance were less than the acceptable daily intake (500 μg/kg bw) determined for linalool (considering an intake of 300 g of tissue per a 60 kg person). The S-(+)-linalool excretion rates in water after 0.5, 1, 2, 6 and 24 h of recovery were 85.10 ± 9.83, 52.45 ± 5.01, 22.67 ± 2.10, 5.62 ± 0.55 and 1.63 ± 0.05 mg/kg h, respectively. About 68% of the total S-(+)-linalool excreted occurred in the first 2 h of recovery, and no volatile metabolites were found at concentrations quantifiable by the method used. Finally, the results of this research provide a scientific basis to guide a future application of S-(+)-linalool as an anesthetic in aquaculture and, mainly, bring evidence that anesthesia (for a prolonged period) with S-(+)-linalool in this species does not cause bioaccumulation at concentrations potentially harmful to human health. However, further pharmacokinetic and toxicological studies must be developed so that this phytochemical can be used with total safety in aquatic species used for human consumption. |
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2022-05-05T18:06:09Z2022-05-05T18:06:09Z2021-06-18http://repositorio.ufsm.br/handle/1/24293S-(+)-linalool is found in essential oils of aromatic plants as Lippia alba. This phytochemical had its sedative/anesthetic activity elucidated in Rhamdia quelen, popularly known as silver catfish. Thus, S-(+)-linalool has become an option as an anesthetic for aquaculture, but its pharmacokinetic profile was unknown until the development of this thesis. Therefore, the objective of this research was to determine the pharmacokinetic profile of S-(+)-linalool in silver catfish. S-(+)-linalool was quantified in plasma, tissue and water (from recovery) samples using gas chromatography with flame ionization detector (GC-FID). For blood and tissue collection, fish (n = 6, for each collection time) were exposed to an immersion bath with S-(+)-linalool (153 mg/L or 180 μL/L) for a maximum of 30 min (0.5 h) and after were transferred to aquariums without the anesthetic. The blood and brain samples were collected at different times in an interval from 0 to 4 hours and the other tissues (kidney, liver, gills and muscle) were collected in the interval from 0 to 24 hours (from the beginning of exposure to the anesthetic). To determine S-(+)-linalool excretion in the water another fish group (n = 6) was anesthetized as previously described and transferred to individual aquariums for up to 48 h. Water samples were collected during this period and later analyzed by GC-FID. The results found indicated that S-(+)-linalool is rapidly absorbed and distributed to the main tissues. The maximum concentrations (Cmax, tissues μg/g and plasma μg/mL) occurred in the magnitude: kidneyplasmabrainlivergillsmuscle (143.15, 129.33, 113.92, 110.03, 54.49 and 20.76, respectively) in 0.5 h (Tmax) with the exception of the brain (0.33 h). The S-(+)-linalool elimination occurs more quickly in the plasma, followed by the liver, kidneys, gills, muscle and brain (T1/2β: 1.36, 3.45, 6.30, 9.96, 11.04 and 57.27 h, respectively). Despite the slow elimination in the brain, all animals recovered from anesthesia within 10 min. Muscle was the second tissue with the highest T 1/2β, however the residual concentrations after 12 hours of clearance were less than the acceptable daily intake (500 μg/kg bw) determined for linalool (considering an intake of 300 g of tissue per a 60 kg person). The S-(+)-linalool excretion rates in water after 0.5, 1, 2, 6 and 24 h of recovery were 85.10 ± 9.83, 52.45 ± 5.01, 22.67 ± 2.10, 5.62 ± 0.55 and 1.63 ± 0.05 mg/kg h, respectively. About 68% of the total S-(+)-linalool excreted occurred in the first 2 h of recovery, and no volatile metabolites were found at concentrations quantifiable by the method used. Finally, the results of this research provide a scientific basis to guide a future application of S-(+)-linalool as an anesthetic in aquaculture and, mainly, bring evidence that anesthesia (for a prolonged period) with S-(+)-linalool in this species does not cause bioaccumulation at concentrations potentially harmful to human health. However, further pharmacokinetic and toxicological studies must be developed so that this phytochemical can be used with total safety in aquatic species used for human consumption.O S-(+)-linalol é encontrado em óleos essenciais de plantas aromáticas como Lippia alba. Este fitoquímico teve sua atividade sedativa/anestésica elucidada em Rhamdia quelen, conhecido popularmente como jundiá. Assim, o S-(+)-linalol tornou-se uma opção como anestésico para aquicultura, porém seu perfil farmacocinético em peixes era desconhecido até o desenvolvimento desta tese. Portanto, o objetivo desta pesquisa foi determinar o perfil farmacocinético de S-(+)-linalol em jundiás. O S-(+)-linalol foi quantificado em amostras de plasma, tecidos e água (da recuperação) através de cromatografia gasosa com detector de ionização de chama (CG-DIC). Para coleta do sangue e tecidos os peixes (n=6, para cada tempo de coleta) foram expostos em banho de imersão com S-(+)-linalol (153 mg/L ou 180 μL/L) por no máximo 30 min (0,5 h) e após transferidos para aquários sem o anestésico. As amostras de sangue e cérebro foram coletadas em diferentes tempos num intervalo de 0 a 4 horas e os demais tecidos (rim, fígado, brânquias e músculo) foram coletados no intervalo de 0 a 24 horas (a partir do início da exposição ao anestésico). Para determinar a excreção de S-(+)-linalol na água outro grupo de peixes (n= 6) foi anestesiado conforme descrito anteriormente e transferidos para aquários individuais por até 48 h. Amostras de água foram coletas durante esse período e posteriormente analisadas por CG-DIC. Os resultados encontrados indicaram que o S-(+)-linalol é rapidamente absorvido e distribuído aos principais tecidos. As concentrações máximas (Cmáx, tecidos μg/g e plasma μg/mL) ocorreram na magnitude: rimplasmacérebrofígadobrânquiasmúsculo (143,15, 129,33, 113,92, 110,03, 54,49 e 20,76, respectivamente) em 0,5 h (Tmáx) com exceção do cérebro (0,33 h). A eliminação de S-(+)-linalol ocorreu de forma mais rápida no plasma, seguido pelo fígado, rins, brânquias, músculo e cérebro (T1/2β: 1,36, 3,45, 6,30, 9,96, 11,04 e 57,27 h, respectivamente). Apesar da eliminação lenta no cérebro, todos os animais recuperaram-se da anestesia em 10 min. O músculo foi o segundo tecido com maior T 1/2β, porém as concentrações residuais após 12 horas de depuração foram menores que a ingestão diária aceitável (500 μg/kg pc) determinada para o linalol (considerando uma ingestão de 300 g de tecido por uma pessoa de 60 kg). As taxas de excreção de S-(+)-linalol na água após 0,5, 1, 2, 6 e 24 h de recuperação foram 85,10 ± 9,83, 52,45 ± 5,01, 22,67 ± 2,10, 5,62 ± 0,55 e 1,63 ± 0,05 mg/kg h, respectivamente. Cerca de 68% do total de S-(+)-linalol excretado ocorreu nas primeiras 2 h de recuperação e não foram encontrados metabólitos voláteis em concentrações quantificáveis pelo método utilizado. Por fim, os resultados desta pesquisa fornecem base científica para nortear uma futura aplicação de S-(+)-linalol como anestésico na aquicultura e, principalmente, trazem evidências que a anestesia (por um período prolongado) com S-(+)-linalol nesta espécie não ocasiona bioacumulação em concentrações potencialmente prejudiciais à saúde humana. Contudo, demais estudos farmacocinéticos e toxicológicos devem ser desenvolvidos para que este fitoquímico possa ser empregado com total segurança em espécies aquáticas destinadas à alimentação humana.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade 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/openAccessAnestésicosDepleção tecidualMonoterpenoidesPeixesProdutos naturaisAnestheticsFishMonoterpenoidsNatural productsTissue depletionCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAFarmacocinética de S-(+)-linalol em jundiás (Rhamdia quelen)Pharmacokinetics of S-(+)-linalool in silver catfish (Rhamdia quelen)info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisBaldisserotto, Bernardohttp://lattes.cnpq.br/1036046601275319Heinzmann, Berta MariaAssis, Helena Cristina da Silva dePilarski, FabianaEmanuelli, TatianaBochi, Guilherme Vargashttp://lattes.cnpq.br/1491614242432359Bianchini, Adriane Erbice2010000000006006006006006006006006004948adb8-9408-43d6-82b1-b9df8481e3daea9cd446-eb61-45e4-9769-35f743d06052c71eb78a-13a7-4ab8-a2c4-6df65e992ed7e62ff99c-b0e8-41fa-9cc8-9b79eda4c882463adddc-369e-4d70-a35b-7116581253907457e618-e257-4f1d-b319-f589826321848942cbc4-805f-4793-b343-70e6ecb45178reponame:Repositório Institucional Manancial UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMLICENSElicense.txtlicense.txttext/plain; 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dc.title.por.fl_str_mv |
Farmacocinética de S-(+)-linalol em jundiás (Rhamdia quelen) |
dc.title.alternative.eng.fl_str_mv |
Pharmacokinetics of S-(+)-linalool in silver catfish (Rhamdia quelen) |
title |
Farmacocinética de S-(+)-linalol em jundiás (Rhamdia quelen) |
spellingShingle |
Farmacocinética de S-(+)-linalol em jundiás (Rhamdia quelen) Bianchini, Adriane Erbice Anestésicos Depleção tecidual Monoterpenoides Peixes Produtos naturais Anesthetics Fish Monoterpenoids Natural products Tissue depletion CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Farmacocinética de S-(+)-linalol em jundiás (Rhamdia quelen) |
title_full |
Farmacocinética de S-(+)-linalol em jundiás (Rhamdia quelen) |
title_fullStr |
Farmacocinética de S-(+)-linalol em jundiás (Rhamdia quelen) |
title_full_unstemmed |
Farmacocinética de S-(+)-linalol em jundiás (Rhamdia quelen) |
title_sort |
Farmacocinética de S-(+)-linalol em jundiás (Rhamdia quelen) |
author |
Bianchini, Adriane Erbice |
author_facet |
Bianchini, Adriane Erbice |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Baldisserotto, Bernardo |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/1036046601275319 |
dc.contributor.advisor-co1.fl_str_mv |
Heinzmann, Berta Maria |
dc.contributor.referee1.fl_str_mv |
Assis, Helena Cristina da Silva de |
dc.contributor.referee2.fl_str_mv |
Pilarski, Fabiana |
dc.contributor.referee3.fl_str_mv |
Emanuelli, Tatiana |
dc.contributor.referee4.fl_str_mv |
Bochi, Guilherme Vargas |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/1491614242432359 |
dc.contributor.author.fl_str_mv |
Bianchini, Adriane Erbice |
contributor_str_mv |
Baldisserotto, Bernardo Heinzmann, Berta Maria Assis, Helena Cristina da Silva de Pilarski, Fabiana Emanuelli, Tatiana Bochi, Guilherme Vargas |
dc.subject.por.fl_str_mv |
Anestésicos Depleção tecidual Monoterpenoides Peixes Produtos naturais |
topic |
Anestésicos Depleção tecidual Monoterpenoides Peixes Produtos naturais Anesthetics Fish Monoterpenoids Natural products Tissue depletion CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
dc.subject.eng.fl_str_mv |
Anesthetics Fish Monoterpenoids Natural products Tissue depletion |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
S-(+)-linalool is found in essential oils of aromatic plants as Lippia alba. This phytochemical had its sedative/anesthetic activity elucidated in Rhamdia quelen, popularly known as silver catfish. Thus, S-(+)-linalool has become an option as an anesthetic for aquaculture, but its pharmacokinetic profile was unknown until the development of this thesis. Therefore, the objective of this research was to determine the pharmacokinetic profile of S-(+)-linalool in silver catfish. S-(+)-linalool was quantified in plasma, tissue and water (from recovery) samples using gas chromatography with flame ionization detector (GC-FID). For blood and tissue collection, fish (n = 6, for each collection time) were exposed to an immersion bath with S-(+)-linalool (153 mg/L or 180 μL/L) for a maximum of 30 min (0.5 h) and after were transferred to aquariums without the anesthetic. The blood and brain samples were collected at different times in an interval from 0 to 4 hours and the other tissues (kidney, liver, gills and muscle) were collected in the interval from 0 to 24 hours (from the beginning of exposure to the anesthetic). To determine S-(+)-linalool excretion in the water another fish group (n = 6) was anesthetized as previously described and transferred to individual aquariums for up to 48 h. Water samples were collected during this period and later analyzed by GC-FID. The results found indicated that S-(+)-linalool is rapidly absorbed and distributed to the main tissues. The maximum concentrations (Cmax, tissues μg/g and plasma μg/mL) occurred in the magnitude: kidneyplasmabrainlivergillsmuscle (143.15, 129.33, 113.92, 110.03, 54.49 and 20.76, respectively) in 0.5 h (Tmax) with the exception of the brain (0.33 h). The S-(+)-linalool elimination occurs more quickly in the plasma, followed by the liver, kidneys, gills, muscle and brain (T1/2β: 1.36, 3.45, 6.30, 9.96, 11.04 and 57.27 h, respectively). Despite the slow elimination in the brain, all animals recovered from anesthesia within 10 min. Muscle was the second tissue with the highest T 1/2β, however the residual concentrations after 12 hours of clearance were less than the acceptable daily intake (500 μg/kg bw) determined for linalool (considering an intake of 300 g of tissue per a 60 kg person). The S-(+)-linalool excretion rates in water after 0.5, 1, 2, 6 and 24 h of recovery were 85.10 ± 9.83, 52.45 ± 5.01, 22.67 ± 2.10, 5.62 ± 0.55 and 1.63 ± 0.05 mg/kg h, respectively. About 68% of the total S-(+)-linalool excreted occurred in the first 2 h of recovery, and no volatile metabolites were found at concentrations quantifiable by the method used. Finally, the results of this research provide a scientific basis to guide a future application of S-(+)-linalool as an anesthetic in aquaculture and, mainly, bring evidence that anesthesia (for a prolonged period) with S-(+)-linalool in this species does not cause bioaccumulation at concentrations potentially harmful to human health. However, further pharmacokinetic and toxicological studies must be developed so that this phytochemical can be used with total safety in aquatic species used for human consumption. |
publishDate |
2021 |
dc.date.issued.fl_str_mv |
2021-06-18 |
dc.date.accessioned.fl_str_mv |
2022-05-05T18:06:09Z |
dc.date.available.fl_str_mv |
2022-05-05T18:06:09Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/24293 |
url |
http://repositorio.ufsm.br/handle/1/24293 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
201000000000 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 600 600 600 600 |
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 |
reponame:Repositório Institucional Manancial UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
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Universidade Federal de Santa Maria (UFSM) |
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UFSM |
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UFSM |
reponame_str |
Repositório Institucional Manancial UFSM |
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Repositório Institucional Manancial UFSM |
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http://repositorio.ufsm.br/bitstream/1/24293/3/license.txt http://repositorio.ufsm.br/bitstream/1/24293/1/TES_PPGFARMACOLOGIA_2021_BIANCHINI_ADRIANE.pdf http://repositorio.ufsm.br/bitstream/1/24293/2/license_rdf |
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MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional Manancial UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
ouvidoria@ufsm.br |
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1808854690658516992 |