Avaliação da toxicidade pré-clínica de Foeniculum vulgare Mill

Detalhes bibliográficos
Autor(a) principal: Branco, Alessandra Camillo da Silveira Castello
Data de Publicação: 2009
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFPB
Texto Completo: https://repositorio.ufpb.br/jspui/handle/tede/6769
Resumo: Foeniculum vulgare Mill. is a plant that has been known and used by mankind since antiquity because of its antimicrobial, analgesic, antiinflammatory, antispasmodic and anxiolytic properties. It is also widely used in the food and cosmetics industries. The objective of the present study was to investigate the chronic preclinical toxicity of the lyophilized crude hydroalcoholic extract (LCHAE) of the fruit of F. vulgare commercialized in sachet form in order to demonstrate the safety of its use by the population, based on Resolution 90/2004 of the Brazilian Regulatory Authorities. In this study, Wistar rats (Rattus norvegicus albinus) were treated orally with 8.5, 25.5 and 76.5 mg/kg of LCHAE for 13 weeks (n=10 per dose and sex). General signs of toxicity, lethality and food and water consumption were evaluated daily, while weight was evaluated weekly and body temperature, glucose levels and behavioral parameters using open-field and rota-rod tests were assessed every two weeks. At the end of treatment, 50% of the animals in each group were sacrificed for blood analysis and 30% were submitted to histopathology. The remaining animals then formed the satellite group that remained under observation for 21 days following treatment to evaluate the reversal and/or appearance of possible toxic effects. During the 13 weeks of treatment, no signs of toxicity were noted and none of the animals died. In the females, there was a reduction in weight and food consumption and an increase in water intake. LCHAE reduced the time both males and females spent on the rotating bar, and reduced ambulation in the females and defecation and rearing in both sexes. In both males and females, a hypoglycemic effect occurred and there was an increase in aspartate aminotransferase (AST) and alkaline phosphatase (ALP), as well as a reduction in platelet count. In the females, there was an increase in alanine transaminase (ALT), leukocytes and neutrophils and a decrease in cholesterol. In the males, a reduction in lymphocytes occurred and there was an increase in monocytes. Histopathology revealed signs of hepatotoxicity including mild portal inflammation with the presence of mononuclear exudate, hepatic lobular necrosis associated with lymphocytic/histiocytic infiltration and mild sinusoidal inflammation. In addition, there were signs of toxicity in the lungs: focal pneumonitis with alveolar septal thickening consisting of mononuclear exudate. In the satellite groups, the majority of the biochemical, hematological and histopathological alterations in the liver were found to persist, suggesting irreversibility. Further studies should be developed to confirm these findings; nevertheless, these results indicate that LCHAE is toxic particularly to the liver and lungs, in both sexes and at the three doses used.
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spelling Avaliação da toxicidade pré-clínica de Foeniculum vulgare MillEvaluation of the cronic preclinical toxicity of Foeniculum vulgare MillFoeniculum vulgare MillFunchoToxicologiaChásFoeniculum vulgare MillSweet fennelToxicologyTeasCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAFoeniculum vulgare Mill. is a plant that has been known and used by mankind since antiquity because of its antimicrobial, analgesic, antiinflammatory, antispasmodic and anxiolytic properties. It is also widely used in the food and cosmetics industries. The objective of the present study was to investigate the chronic preclinical toxicity of the lyophilized crude hydroalcoholic extract (LCHAE) of the fruit of F. vulgare commercialized in sachet form in order to demonstrate the safety of its use by the population, based on Resolution 90/2004 of the Brazilian Regulatory Authorities. In this study, Wistar rats (Rattus norvegicus albinus) were treated orally with 8.5, 25.5 and 76.5 mg/kg of LCHAE for 13 weeks (n=10 per dose and sex). General signs of toxicity, lethality and food and water consumption were evaluated daily, while weight was evaluated weekly and body temperature, glucose levels and behavioral parameters using open-field and rota-rod tests were assessed every two weeks. At the end of treatment, 50% of the animals in each group were sacrificed for blood analysis and 30% were submitted to histopathology. The remaining animals then formed the satellite group that remained under observation for 21 days following treatment to evaluate the reversal and/or appearance of possible toxic effects. During the 13 weeks of treatment, no signs of toxicity were noted and none of the animals died. In the females, there was a reduction in weight and food consumption and an increase in water intake. LCHAE reduced the time both males and females spent on the rotating bar, and reduced ambulation in the females and defecation and rearing in both sexes. In both males and females, a hypoglycemic effect occurred and there was an increase in aspartate aminotransferase (AST) and alkaline phosphatase (ALP), as well as a reduction in platelet count. In the females, there was an increase in alanine transaminase (ALT), leukocytes and neutrophils and a decrease in cholesterol. In the males, a reduction in lymphocytes occurred and there was an increase in monocytes. Histopathology revealed signs of hepatotoxicity including mild portal inflammation with the presence of mononuclear exudate, hepatic lobular necrosis associated with lymphocytic/histiocytic infiltration and mild sinusoidal inflammation. In addition, there were signs of toxicity in the lungs: focal pneumonitis with alveolar septal thickening consisting of mononuclear exudate. In the satellite groups, the majority of the biochemical, hematological and histopathological alterations in the liver were found to persist, suggesting irreversibility. Further studies should be developed to confirm these findings; nevertheless, these results indicate that LCHAE is toxic particularly to the liver and lungs, in both sexes and at the three doses used.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorFoeniculum vulgare Mill. é uma planta usada pelos humanos desde a antiguidade, devido às suas atividades antimicrobiana, analgésica, anti-inflamatória, antiespasmódica e ansiolítica, além de ser uma espécie utilizada na indústria de alimentos e cosméticos. O presente trabalho objetivou investigar a toxicidade préclínica crônica do extrato hidroalcoólico bruto liofilizado do fruto de F. vulgare (saches), na perspectiva de avaliar a segurança de seu uso pela população, com base na Resolução nº 90/2004 da Agência Nacional de Vigilância Sanitária e algumas modificações. Neste estudo, ratos Wistar (Rattus norvegicus albinus) foram tratados por via oral (v.o.) com as doses 8,5; 25,5 e 76,5 mg/kg do EHABL durante 13 semanas (n=10 por dose e sexo). Foram avaliados diariamente sinais gerais de toxicidade, letalidade, consumo de alimentos e água; semanalmente, variação da evolução ponderal; e, quinzenalmente, temperatura corporal, glicemia e parâmetros comportamentais através dos testes de campo aberto e da barra giratória. Ao final do tratamento, 50 % dos animais de cada grupo foram sacrificados para análises sanguíneas, dos quais 30 % passaram por investigação histopatológica. O restante dos animais passou a fazer parte do grupo satélite, os quais permaneceram em observação 21 dias após o tratamento, para a verificação da reversão e/ou aparecimento de possíveis efeitos tóxicos. Na triagem farmacológica comportamental, não se observaram características de toxicidade e mortes durante as 13 semanas de tratamento. Em fêmeas, houve uma diminuição no peso corpóreo e no consumo de alimentos, com um aumento no consumo de água. O EHABL reduziu o tempo de permanência na barra giratória em ambos os sexos; diminuiu a ambulação em fêmeas; e reduziu os parâmetros defecação e levantar em ambos os sexos. Em machos e fêmeas, houve um efeito hipoglicemiante, aumento da aspartato aminotransferase (AST) e fosfatase alcalina (FAL), com redução das plaquetas. Em fêmeas, ocorreu um aumento da alanina aminotransferase (ALT), leucócitos, neutrófilos e diminuição do colesterol. Nos machos, ocorreu diminuição do número de linfócitos e aumento do número de monócitos. A análise histopatológica mostrou indícios de hepatotoxicidade, como portite discreta com a presença de exsudação mononuclear, necrose lobular hepática associada a afluxo linfoistiocitário e inflamação sinusoidal discreta. Adicionalmente, o pulmão apresentou sinais de toxicidade: pneumonite focal com espessamento de septo alveolar por exsudação mononuclear. Nos grupos satélites, observou-se que a maioria das alterações bioquímicas, hematológicas e histopatológicas, no fígado, persistiram, mostrando a necessidade de maiores investigações. Portanto, de acordo com os resultados obtidos, o EHABL apresentou uma toxicidade significativa, especialmente no fígado e pulmão, em ambos os sexos e nas três doses utilizadas.Universidade Federal da Paraí­baBRFarmacologiaPrograma de Pós Graduação em Produtos Naturais e Sintéticos BioativosUFPBAlmeida, Reinaldo Nobrega dehttp://lattes.cnpq.br/5034028656386134Diniz, Margareth de Fátima Formiga Melohttp://lattes.cnpq.br/4173269414899195Branco, Alessandra Camillo da Silveira Castello2015-05-14T12:59:47Z2018-07-21T00:25:04Z2010-01-062018-07-21T00:25:04Z2009-10-29info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfBRANCO, Alessandra Camillo da Silveira Castello. Evaluation of the cronic preclinical toxicity of Foeniculum vulgare Mill. 2009. 136 f. Tese (Doutorado em Farmacologia) - Universidade Federal da Paraí­ba, João Pessoa, 2009.https://repositorio.ufpb.br/jspui/handle/tede/6769porinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2018-09-06T01:53:49Zoai:repositorio.ufpb.br:tede/6769Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2018-09-06T01:53:49Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false
dc.title.none.fl_str_mv Avaliação da toxicidade pré-clínica de Foeniculum vulgare Mill
Evaluation of the cronic preclinical toxicity of Foeniculum vulgare Mill
title Avaliação da toxicidade pré-clínica de Foeniculum vulgare Mill
spellingShingle Avaliação da toxicidade pré-clínica de Foeniculum vulgare Mill
Branco, Alessandra Camillo da Silveira Castello
Foeniculum vulgare Mill
Funcho
Toxicologia
Chás
Foeniculum vulgare Mill
Sweet fennel
Toxicology
Teas
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
title_short Avaliação da toxicidade pré-clínica de Foeniculum vulgare Mill
title_full Avaliação da toxicidade pré-clínica de Foeniculum vulgare Mill
title_fullStr Avaliação da toxicidade pré-clínica de Foeniculum vulgare Mill
title_full_unstemmed Avaliação da toxicidade pré-clínica de Foeniculum vulgare Mill
title_sort Avaliação da toxicidade pré-clínica de Foeniculum vulgare Mill
author Branco, Alessandra Camillo da Silveira Castello
author_facet Branco, Alessandra Camillo da Silveira Castello
author_role author
dc.contributor.none.fl_str_mv Almeida, Reinaldo Nobrega de
http://lattes.cnpq.br/5034028656386134
Diniz, Margareth de Fátima Formiga Melo
http://lattes.cnpq.br/4173269414899195
dc.contributor.author.fl_str_mv Branco, Alessandra Camillo da Silveira Castello
dc.subject.por.fl_str_mv Foeniculum vulgare Mill
Funcho
Toxicologia
Chás
Foeniculum vulgare Mill
Sweet fennel
Toxicology
Teas
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
topic Foeniculum vulgare Mill
Funcho
Toxicologia
Chás
Foeniculum vulgare Mill
Sweet fennel
Toxicology
Teas
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
description Foeniculum vulgare Mill. is a plant that has been known and used by mankind since antiquity because of its antimicrobial, analgesic, antiinflammatory, antispasmodic and anxiolytic properties. It is also widely used in the food and cosmetics industries. The objective of the present study was to investigate the chronic preclinical toxicity of the lyophilized crude hydroalcoholic extract (LCHAE) of the fruit of F. vulgare commercialized in sachet form in order to demonstrate the safety of its use by the population, based on Resolution 90/2004 of the Brazilian Regulatory Authorities. In this study, Wistar rats (Rattus norvegicus albinus) were treated orally with 8.5, 25.5 and 76.5 mg/kg of LCHAE for 13 weeks (n=10 per dose and sex). General signs of toxicity, lethality and food and water consumption were evaluated daily, while weight was evaluated weekly and body temperature, glucose levels and behavioral parameters using open-field and rota-rod tests were assessed every two weeks. At the end of treatment, 50% of the animals in each group were sacrificed for blood analysis and 30% were submitted to histopathology. The remaining animals then formed the satellite group that remained under observation for 21 days following treatment to evaluate the reversal and/or appearance of possible toxic effects. During the 13 weeks of treatment, no signs of toxicity were noted and none of the animals died. In the females, there was a reduction in weight and food consumption and an increase in water intake. LCHAE reduced the time both males and females spent on the rotating bar, and reduced ambulation in the females and defecation and rearing in both sexes. In both males and females, a hypoglycemic effect occurred and there was an increase in aspartate aminotransferase (AST) and alkaline phosphatase (ALP), as well as a reduction in platelet count. In the females, there was an increase in alanine transaminase (ALT), leukocytes and neutrophils and a decrease in cholesterol. In the males, a reduction in lymphocytes occurred and there was an increase in monocytes. Histopathology revealed signs of hepatotoxicity including mild portal inflammation with the presence of mononuclear exudate, hepatic lobular necrosis associated with lymphocytic/histiocytic infiltration and mild sinusoidal inflammation. In addition, there were signs of toxicity in the lungs: focal pneumonitis with alveolar septal thickening consisting of mononuclear exudate. In the satellite groups, the majority of the biochemical, hematological and histopathological alterations in the liver were found to persist, suggesting irreversibility. Further studies should be developed to confirm these findings; nevertheless, these results indicate that LCHAE is toxic particularly to the liver and lungs, in both sexes and at the three doses used.
publishDate 2009
dc.date.none.fl_str_mv 2009-10-29
2010-01-06
2015-05-14T12:59:47Z
2018-07-21T00:25:04Z
2018-07-21T00:25:04Z
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 BRANCO, Alessandra Camillo da Silveira Castello. Evaluation of the cronic preclinical toxicity of Foeniculum vulgare Mill. 2009. 136 f. Tese (Doutorado em Farmacologia) - Universidade Federal da Paraí­ba, João Pessoa, 2009.
https://repositorio.ufpb.br/jspui/handle/tede/6769
identifier_str_mv BRANCO, Alessandra Camillo da Silveira Castello. Evaluation of the cronic preclinical toxicity of Foeniculum vulgare Mill. 2009. 136 f. Tese (Doutorado em Farmacologia) - Universidade Federal da Paraí­ba, João Pessoa, 2009.
url https://repositorio.ufpb.br/jspui/handle/tede/6769
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eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal da Paraí­ba
BR
Farmacologia
Programa de Pós Graduação em Produtos Naturais e Sintéticos Bioativos
UFPB
publisher.none.fl_str_mv Universidade Federal da Paraí­ba
BR
Farmacologia
Programa de Pós Graduação em Produtos Naturais e Sintéticos Bioativos
UFPB
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da UFPB
instname:Universidade Federal da Paraíba (UFPB)
instacron:UFPB
instname_str Universidade Federal da Paraíba (UFPB)
instacron_str UFPB
institution UFPB
reponame_str Biblioteca Digital de Teses e Dissertações da UFPB
collection Biblioteca Digital de Teses e Dissertações da UFPB
repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)
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