Estudo toxicológico pré-clínico de Jatropha gossypiifolia L.

Detalhes bibliográficos
Autor(a) principal: Mariz, Saulo Rios
Data de Publicação: 2007
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/6736
Resumo: The Jatropha gossypiifolia L.(Euphorbiaceae), also known in Brazil as pião-roxo , is a plant with high toxicity. However, some of its therapeutic uses have been proved by experimental studies including a recent paper about the hypotensive effect of this plant. In order to contribute to the development of a herbal drug from this species, this work presents a toxicity assessment in rats with the ethanolic extract (EE) from aerial parts of Jatropha gossypiifolia L. according to Brazilian law (ANVISA-RE 90/2004). In the acute toxicity test we treated Wistar rats (Ratus norvegicus albinus) with the EE in doses of up to 5 g/kg body weight (p.o.). Each group was observed, for 14 days after the treatment, in points such as toxicity signs, lethality, body weight gain and food and water consumption. After this period, the animals which survived were killed for biochemical, hematological and histopathologic analysis. In the chronic toxicity assessment, the rats were handed out on three experimental groups (45 mg/kg, 135 mg/kg and 405 mg/kg). Each group (n=10 per gender and dose) was dosed daily by gavage for a period of 13 weeks. During the treatment, in addition to the parameters cited above, body temperature, tail glucose level and changes in behavior were analyzed (Open field and Rota Rod). At the end of treatment, 40% of animals from each group were killed for the analysis of those parameters already cited in the acute study. The acute treatment shows that only doses equal or higher than 1.8 g/kg body weight (p.o.) cause signals of toxicity as neurological depression and digestive disorders. We observed weight loss and a hind limb paralysis in males (doses 4 and 5 g/kg p.o.). Only in males that survived to higher dose treatment (5 g/kg p.o.) the extract reduced the food intake significantly. This dose also promotes weight loss in females without reduction of food intake. In males treated with 5 g/kg (p.o.), some biochemical, hematological and histopathologic alterations suggest important acute toxicity in the liver, the kidney, the blood and the lung. The LD50 was between 4 and 5 g/kg (p.o.) to males and was higher than 5 g/kg (p.o.) to females. These results indicate that acute toxicity from EE is not significant because the alterations happened just in high doses. However, the neurological depression and digestive disorders were confirmed by chronic evaluation. The lethality among males was 46.6 % (405 mg/kg p.o.), 13,3% (135 mg/kg p.o.) and among females was 13.3 % (doses of 135 mg/kg and 405 mg/kg p.o.). The EE reduces the body weight gain (males 405 mg/kg p.o.). At the colon temperature the extract produces alterations that were not related to the doses in both sexes. In some rats, the product increased glucose level in a reversible way. The locomotion was reduced in females (405 mg/kg p.o.). The increase of total proteins (males 405 mg/kg p.o.) was discrete. It was observed an important increase of glucose level among males (45 mg/Kg p.o.). We also found a discrete anaemia in males (405 mg/kg p.o.) and a increased level of platelet in females of satellite group (135mg/Kg). The histopathologic analysis confirmed the toxicity in liver, kidney and lung. These data show the high chronic toxicity from the product. We propose a chemical refinement on the ethanolic extract to get new fractions with a better risk/benefit relation.
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spelling Estudo toxicológico pré-clínico de Jatropha gossypiifolia L.ToxicologiaPlantas TóxicasJatropha gossypiifolia L.Pião-roxoToxicologyToxic PlantsJatropha gossypiifolia L.Pião-roxoCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAThe Jatropha gossypiifolia L.(Euphorbiaceae), also known in Brazil as pião-roxo , is a plant with high toxicity. However, some of its therapeutic uses have been proved by experimental studies including a recent paper about the hypotensive effect of this plant. In order to contribute to the development of a herbal drug from this species, this work presents a toxicity assessment in rats with the ethanolic extract (EE) from aerial parts of Jatropha gossypiifolia L. according to Brazilian law (ANVISA-RE 90/2004). In the acute toxicity test we treated Wistar rats (Ratus norvegicus albinus) with the EE in doses of up to 5 g/kg body weight (p.o.). Each group was observed, for 14 days after the treatment, in points such as toxicity signs, lethality, body weight gain and food and water consumption. After this period, the animals which survived were killed for biochemical, hematological and histopathologic analysis. In the chronic toxicity assessment, the rats were handed out on three experimental groups (45 mg/kg, 135 mg/kg and 405 mg/kg). Each group (n=10 per gender and dose) was dosed daily by gavage for a period of 13 weeks. During the treatment, in addition to the parameters cited above, body temperature, tail glucose level and changes in behavior were analyzed (Open field and Rota Rod). At the end of treatment, 40% of animals from each group were killed for the analysis of those parameters already cited in the acute study. The acute treatment shows that only doses equal or higher than 1.8 g/kg body weight (p.o.) cause signals of toxicity as neurological depression and digestive disorders. We observed weight loss and a hind limb paralysis in males (doses 4 and 5 g/kg p.o.). Only in males that survived to higher dose treatment (5 g/kg p.o.) the extract reduced the food intake significantly. This dose also promotes weight loss in females without reduction of food intake. In males treated with 5 g/kg (p.o.), some biochemical, hematological and histopathologic alterations suggest important acute toxicity in the liver, the kidney, the blood and the lung. The LD50 was between 4 and 5 g/kg (p.o.) to males and was higher than 5 g/kg (p.o.) to females. These results indicate that acute toxicity from EE is not significant because the alterations happened just in high doses. However, the neurological depression and digestive disorders were confirmed by chronic evaluation. The lethality among males was 46.6 % (405 mg/kg p.o.), 13,3% (135 mg/kg p.o.) and among females was 13.3 % (doses of 135 mg/kg and 405 mg/kg p.o.). The EE reduces the body weight gain (males 405 mg/kg p.o.). At the colon temperature the extract produces alterations that were not related to the doses in both sexes. In some rats, the product increased glucose level in a reversible way. The locomotion was reduced in females (405 mg/kg p.o.). The increase of total proteins (males 405 mg/kg p.o.) was discrete. It was observed an important increase of glucose level among males (45 mg/Kg p.o.). We also found a discrete anaemia in males (405 mg/kg p.o.) and a increased level of platelet in females of satellite group (135mg/Kg). The histopathologic analysis confirmed the toxicity in liver, kidney and lung. These data show the high chronic toxicity from the product. We propose a chemical refinement on the ethanolic extract to get new fractions with a better risk/benefit relation.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorA espécie Jatropha gossypiifolia L. (Euphorbiaceae), também denominada piãoroxo, é uma planta reconhecidamente tóxica. Todavia, alguns dos vários usos dessa planta na medicina popular têm sido comprovados por estudos experimentais, dentre os quais se destaca a recente demonstração do seu efeito hipotensor. Com o objetivo de contribuir para o desenvolvimento de um medicamento fitoterápico anti-hipertensivo, a partir da referida espécie, este trabalho se propôs a avaliar a toxicidade pré-clínica (aguda e crônica) do extrato etanólico (EE) de partes aéreas (folhas e caules) de Jatropha gossypiifolia L. de acordo com a norma brasileira (ANVISA-RE 90/2004). No estudo toxicológico agudo, ratos Wistar (Ratus norvegicus albinus) foram tratados (v.o.) com o produto (n = 6 por dose e sexo) em doses de até 5 g/kg de peso corpóreo. Durante 14 dias após o tratamento foram observados: sinais tóxicos gerais, letalidade, evolução ponderal, consumo de água e alimentos. Após esse período, os animais sobreviventes foram sacrificados para análise de parâmetros sangüíneos e histopatológicos. No estudo crônico os animais foram tratados com doses de 45 mg/kg, 135 mg/kg e 405 mg/kg durante 13 semanas (n = 10 por dose e sexo). Durante o tratamento, além dos parâmetros já citados, avaliou-se temperatura corporal, glicemia caudal e alterações comportamentais (Campo Aberto e Rota Rod). Ao final do tratamento, 40% dos animais de cada grupo foram sacrificados para análise dos parâmetros já citados no estudo agudo. No tratamento agudo apenas nos animais tratados com dose igual ou superior a 1,8 g/kg (v.o.) observou-se sinais de redução da atividade do SNC e distúrbios gastrintestinais. Em machos das doses de 4,0 e 5,0 g/kg (v.o.), a perda gradativa de peso e a paralisia do trem posterior foram sinais anteriores ao óbito. Somente em machos sobreviventes à dose de 5 g/kg (v.o.) o extrato reduziu o consumo de alimentos de modo significativo. Essa dose também reduziu a evolução ponderal de fêmeas sem alterar a ingestão de alimentos desses animais. Alterações laboratoriais e histopatológicas só ocorreram em machos tratados com a maior dose sugerindo hepatotoxicidade, nefrotoxicidade, além de leucopenia e agravo pulmonar. A dose letal mediana (DL50) foi estimada entre 4,0 e 5,0 g/kg para machos e foi superior a 5 g/kg em fêmeas. Esses resultados indicam uma toxicidade aguda oral relativamente baixa considerando que as alterações só ocorreram em altas doses. No estudo crônico confirmou-se a depressão do SNC e distúrbios gastrintestinais observados no agudo. A letalidade foi de 46,6% entre os machos da maior dose experimental (405 mg/kg v.o.) e de 13,3 % tanto entre fêmeas da maior dose quanto entre os animais tratados com 135 mg/kg (v.o.) do produto. O extrato reduziu a evolução ponderal de machos da dose de 405 mg/kg (v.o.). A temperatura colônica foi inicialmente elevada e posteriormente reduzida de modo não proporcional à dose e em ambos os sexos. O produto apresentou efeito hiperglicemiante reversível (ausente no grupo satélite) em alguns animais. A atividade motora foi reduzida em fêmeas da maior dose. A elevação de proteínas totais em machos da maior dose foi clinicamente discreta e reversível. Ocorreu importante hiperglicemia entre machos da menor dose. Encontrou-se anemia leve em machos tratados com 405 mg/kg (v.o.) e aumento de plaquetas em fêmeas satélites (135mg/Kg). A análise histopatológica também corrobora a hepatotoxicidade, toxicidade renal e apresenta danos pulmonares. Esses resultados demonstram a elevada toxicidade crônica do produto e nos permitem sugerir refinamento químico do extrato com posterior avaliação da manutenção do efeito hipotensor e eventual toxicidade.Universidade Federal da Paraí­baBRFarmacologiaPrograma de Pós Graduação em Produtos Naturais e Sintéticos BioativosUFPBMedeiros, Isac Almeida dehttp://lattes.cnpq.br/3412816427200150Diniz, Margareth de Fátima Formiga Melohttp://lattes.cnpq.br/4173269414899195Mariz, Saulo Rios2015-05-14T12:59:37Z2018-07-21T00:26:09Z2009-10-302018-07-21T00:26:09Z2007-04-02info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfMARIZ, Saulo Rios. Estudo toxicológico pré-clínico de Jatropha gossypiifolia L.. 2007. 191 f. Tese (Doutorado em Farmacologia) - Universidade Federal da Paraí­ba, João Pessoa, 2007.https://repositorio.ufpb.br/jspui/handle/tede/6736porinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2018-09-06T02:39:10Zoai:repositorio.ufpb.br:tede/6736Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2018-09-06T02:39:10Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false
dc.title.none.fl_str_mv Estudo toxicológico pré-clínico de Jatropha gossypiifolia L.
title Estudo toxicológico pré-clínico de Jatropha gossypiifolia L.
spellingShingle Estudo toxicológico pré-clínico de Jatropha gossypiifolia L.
Mariz, Saulo Rios
Toxicologia
Plantas Tóxicas
Jatropha gossypiifolia L.
Pião-roxo
Toxicology
Toxic Plants
Jatropha gossypiifolia L.
Pião-roxo
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
title_short Estudo toxicológico pré-clínico de Jatropha gossypiifolia L.
title_full Estudo toxicológico pré-clínico de Jatropha gossypiifolia L.
title_fullStr Estudo toxicológico pré-clínico de Jatropha gossypiifolia L.
title_full_unstemmed Estudo toxicológico pré-clínico de Jatropha gossypiifolia L.
title_sort Estudo toxicológico pré-clínico de Jatropha gossypiifolia L.
author Mariz, Saulo Rios
author_facet Mariz, Saulo Rios
author_role author
dc.contributor.none.fl_str_mv Medeiros, Isac Almeida de
http://lattes.cnpq.br/3412816427200150
Diniz, Margareth de Fátima Formiga Melo
http://lattes.cnpq.br/4173269414899195
dc.contributor.author.fl_str_mv Mariz, Saulo Rios
dc.subject.por.fl_str_mv Toxicologia
Plantas Tóxicas
Jatropha gossypiifolia L.
Pião-roxo
Toxicology
Toxic Plants
Jatropha gossypiifolia L.
Pião-roxo
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
topic Toxicologia
Plantas Tóxicas
Jatropha gossypiifolia L.
Pião-roxo
Toxicology
Toxic Plants
Jatropha gossypiifolia L.
Pião-roxo
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
description The Jatropha gossypiifolia L.(Euphorbiaceae), also known in Brazil as pião-roxo , is a plant with high toxicity. However, some of its therapeutic uses have been proved by experimental studies including a recent paper about the hypotensive effect of this plant. In order to contribute to the development of a herbal drug from this species, this work presents a toxicity assessment in rats with the ethanolic extract (EE) from aerial parts of Jatropha gossypiifolia L. according to Brazilian law (ANVISA-RE 90/2004). In the acute toxicity test we treated Wistar rats (Ratus norvegicus albinus) with the EE in doses of up to 5 g/kg body weight (p.o.). Each group was observed, for 14 days after the treatment, in points such as toxicity signs, lethality, body weight gain and food and water consumption. After this period, the animals which survived were killed for biochemical, hematological and histopathologic analysis. In the chronic toxicity assessment, the rats were handed out on three experimental groups (45 mg/kg, 135 mg/kg and 405 mg/kg). Each group (n=10 per gender and dose) was dosed daily by gavage for a period of 13 weeks. During the treatment, in addition to the parameters cited above, body temperature, tail glucose level and changes in behavior were analyzed (Open field and Rota Rod). At the end of treatment, 40% of animals from each group were killed for the analysis of those parameters already cited in the acute study. The acute treatment shows that only doses equal or higher than 1.8 g/kg body weight (p.o.) cause signals of toxicity as neurological depression and digestive disorders. We observed weight loss and a hind limb paralysis in males (doses 4 and 5 g/kg p.o.). Only in males that survived to higher dose treatment (5 g/kg p.o.) the extract reduced the food intake significantly. This dose also promotes weight loss in females without reduction of food intake. In males treated with 5 g/kg (p.o.), some biochemical, hematological and histopathologic alterations suggest important acute toxicity in the liver, the kidney, the blood and the lung. The LD50 was between 4 and 5 g/kg (p.o.) to males and was higher than 5 g/kg (p.o.) to females. These results indicate that acute toxicity from EE is not significant because the alterations happened just in high doses. However, the neurological depression and digestive disorders were confirmed by chronic evaluation. The lethality among males was 46.6 % (405 mg/kg p.o.), 13,3% (135 mg/kg p.o.) and among females was 13.3 % (doses of 135 mg/kg and 405 mg/kg p.o.). The EE reduces the body weight gain (males 405 mg/kg p.o.). At the colon temperature the extract produces alterations that were not related to the doses in both sexes. In some rats, the product increased glucose level in a reversible way. The locomotion was reduced in females (405 mg/kg p.o.). The increase of total proteins (males 405 mg/kg p.o.) was discrete. It was observed an important increase of glucose level among males (45 mg/Kg p.o.). We also found a discrete anaemia in males (405 mg/kg p.o.) and a increased level of platelet in females of satellite group (135mg/Kg). The histopathologic analysis confirmed the toxicity in liver, kidney and lung. These data show the high chronic toxicity from the product. We propose a chemical refinement on the ethanolic extract to get new fractions with a better risk/benefit relation.
publishDate 2007
dc.date.none.fl_str_mv 2007-04-02
2009-10-30
2015-05-14T12:59:37Z
2018-07-21T00:26:09Z
2018-07-21T00:26:09Z
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 MARIZ, Saulo Rios. Estudo toxicológico pré-clínico de Jatropha gossypiifolia L.. 2007. 191 f. Tese (Doutorado em Farmacologia) - Universidade Federal da Paraí­ba, João Pessoa, 2007.
https://repositorio.ufpb.br/jspui/handle/tede/6736
identifier_str_mv MARIZ, Saulo Rios. Estudo toxicológico pré-clínico de Jatropha gossypiifolia L.. 2007. 191 f. Tese (Doutorado em Farmacologia) - Universidade Federal da Paraí­ba, João Pessoa, 2007.
url https://repositorio.ufpb.br/jspui/handle/tede/6736
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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
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