Avaliação das toxicidades aguda e subaguda da Olea europaea L. e seu efeito no metabolismo de ratos diabéticos

Detalhes bibliográficos
Ano de defesa: 2016
Autor(a) principal: Guex, Camille Gaube
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
dARK ID: ark:/26339/001300000g520
Idioma: por
Instituição de defesa: Universidade Federal de Santa Maria
Brasil
Farmacologia
UFSM
Programa de Pós-Graduação em Farmacologia
Centro de Ciências da Saúde
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://repositorio.ufsm.br/handle/1/20222
Resumo: Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, insulin resistance and dyslipidemia. It is widely distributed worldwide, affecting millions of people and can lead to serious complications. Olive (Olea europaea L.) has important pharmacological activities, including antioxidant, anti-inflammatory and hypoglycemic. However, studies about its toxicity are still limited in the literature. Therefore, the aim of this study was to investigate the acute and subacute oral toxicities of the tincture of olive leaves (TOL) and evaluate the effect of TOL in metabolism of diabetic rats induced by high-fat diet and low dose of streptozotocin (STZ). In acute toxicity, a single dose of 2000 mg/kg of TOL was administered and observation was during 14 days, including behavior changes and signs of toxicity. In subacute study, TOL was administered for 28 days in the doses of 100, 200 and 400 mg/kg. Both treatments were by oral gavage in male and female rats and body weight was recorded. At the end of the experiment, blood was collected for biochemical and hematological analyses. The dose of 2000 mg /kg did not induce mortality or signs of toxicity. Animals exposed to repeated doses did not show abnormalities or hematological changes. At dose of 400 mg/kg, TOL increased levels of urea and reduced AST activity in males when compared to the different groups. Glucose levels decreased in males and females treated with TOL at different doses compared to controls. There was no significant change in body weight of animals in acute and subacute treatments. For the induction of experimental DM, animals were fed with a high-fat diet for 4 weeks and then was administered streptozotocin (35 mg/kg), via i.p., while the control group received regular diet and only citrate buffer via i.p. Rats with glucose levels above 200 mg/dL were considered diabetic. The animals were divided into 5 groups: Group I. negative control; Group II. diabetic treated with ethanol (51%); group III. diabetic treated with metformin (250 mg/kg) and groups IV and V. diabetic treated with TOL (200 mg/kg and 400 mg/kg, respectively). The administration was by oral gavage, daily, for 10 weeks. Hematologic and biochemical analyses were performed, as well as lipid peroxidation and antioxidant activity. The ALT activity was reduced in the groups treated with metformin and TOL (200 mg/kg) when compared to the control group and an increase in urea was observed in the group treated with TOL (200 mg/kg) compared to the control group. Treatment with TOL improved the levels of inflammatory markers (IL-6, IL-10, TNF-α and INF-γ) and adipokines (leptin, adiponectin and resistin) when compared to diabetic animals. There was no significant difference in MDA levels and no changes were observed in antioxidant activities. These results indicate that the exposure to a single or repeated doses did not induce toxicity and a potential anti-diabetic activity of tincture of olive leaves, but more studies are needed to validate its clinical effects and its safety for use in humans.
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spelling Avaliação das toxicidades aguda e subaguda da Olea europaea L. e seu efeito no metabolismo de ratos diabéticosAssessment of acute and subacute toxicities of Olea europaea L. and its effect in metabolism of diabetic ratsDiabetes mellitusOlivaFolhasToxicidadeOliveLeavesToxicityCNPQ::CIENCIAS DA SAUDE::FARMACIADiabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, insulin resistance and dyslipidemia. It is widely distributed worldwide, affecting millions of people and can lead to serious complications. Olive (Olea europaea L.) has important pharmacological activities, including antioxidant, anti-inflammatory and hypoglycemic. However, studies about its toxicity are still limited in the literature. Therefore, the aim of this study was to investigate the acute and subacute oral toxicities of the tincture of olive leaves (TOL) and evaluate the effect of TOL in metabolism of diabetic rats induced by high-fat diet and low dose of streptozotocin (STZ). In acute toxicity, a single dose of 2000 mg/kg of TOL was administered and observation was during 14 days, including behavior changes and signs of toxicity. In subacute study, TOL was administered for 28 days in the doses of 100, 200 and 400 mg/kg. Both treatments were by oral gavage in male and female rats and body weight was recorded. At the end of the experiment, blood was collected for biochemical and hematological analyses. The dose of 2000 mg /kg did not induce mortality or signs of toxicity. Animals exposed to repeated doses did not show abnormalities or hematological changes. At dose of 400 mg/kg, TOL increased levels of urea and reduced AST activity in males when compared to the different groups. Glucose levels decreased in males and females treated with TOL at different doses compared to controls. There was no significant change in body weight of animals in acute and subacute treatments. For the induction of experimental DM, animals were fed with a high-fat diet for 4 weeks and then was administered streptozotocin (35 mg/kg), via i.p., while the control group received regular diet and only citrate buffer via i.p. Rats with glucose levels above 200 mg/dL were considered diabetic. The animals were divided into 5 groups: Group I. negative control; Group II. diabetic treated with ethanol (51%); group III. diabetic treated with metformin (250 mg/kg) and groups IV and V. diabetic treated with TOL (200 mg/kg and 400 mg/kg, respectively). The administration was by oral gavage, daily, for 10 weeks. Hematologic and biochemical analyses were performed, as well as lipid peroxidation and antioxidant activity. The ALT activity was reduced in the groups treated with metformin and TOL (200 mg/kg) when compared to the control group and an increase in urea was observed in the group treated with TOL (200 mg/kg) compared to the control group. Treatment with TOL improved the levels of inflammatory markers (IL-6, IL-10, TNF-α and INF-γ) and adipokines (leptin, adiponectin and resistin) when compared to diabetic animals. There was no significant difference in MDA levels and no changes were observed in antioxidant activities. These results indicate that the exposure to a single or repeated doses did not induce toxicity and a potential anti-diabetic activity of tincture of olive leaves, but more studies are needed to validate its clinical effects and its safety for use in humans.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESO diabetes mellitus (DM) é uma doença metabólica caracterizada por hiperglicemia, resistência à insulina e dislipidemia. É amplamente distribuída pelo mundo e afeta milhões de pessoas, podendo causar sérias complicações. A oliva (Olea europaea L.) possui importantes atividades farmacológicas, entre elas, antioxidante, anti-inflamatória e hipoglicêmica. Entretanto, estudos sobre sua toxicidade ainda são limitados na literatura. Assim, o objetivo do trabalho foi investigar as toxicidades oral aguda e subaguda da tintura das folhas de oliva (TOL) e avaliar o efeito da TOL no metabolismo de ratos diabéticos induzidos por dieta hipercalórica e baixa dose de estreptozotocina (STZ). Na toxicidade aguda, uma única dose 2000 mg/kg de TOL foi administrada e a observação foi feita durante 14 dias e incluiu mudanças de comportamento e sinais de toxicidade. No estudo subagudo, a TOL foi administrada durante 28 dias nas doses de 100, 200 e 400 mg/kg. Ambos tratamentos foram via oral (gavagem) em ratos machos e fêmeas e o peso corporal foi registrado. Ao final dos experimentos, o sangue foi coletado para análises bioquímicas e hematológicas. A dose de 2000 mg/kg não induziu mortalidade ou sinais de toxicidade. Os animais expostos às doses repetidas não apresentaram anormalidades ou mudanças hematológicas. Na dose de 400 mg/kg, a TOL aumentou os níveis de ureia e reduziu a atividade da AST em machos quando comparado aos diferentes grupos. Os níveis de glicose reduziram em machos e fêmeas tratados com TOL em diferentes doses quando comparados ao grupo controle. Não foi observada mudança significativa no peso corporal dos animais nos tratamentos agudo e subagudo. Para indução do DM, os animais foram alimentados com dieta hipercalórica durante 4 semanas e, então, administrado STZ (35 mg/kg), via i.p., enquanto que o grupo controle recebeu ração padrão e apenas o tampão citrato, via i.p. Os ratos que apresentaram glicemia maior que 200 mg/dL foram considerados diabéticos. Os animais foram divididos em 5 grupos: grupo I. controle negativo; grupo II. diabéticos tratados com etanol; grupo III. diabéticos tratados com metformina (250 mg/kg) e grupos IV e V. diabéticos tratados com TOL (200 mg/kg e 400 mg/kg, respectivamente). A administração foi via oral, diariamente, durante 10 semanas. Análises bioquímicas e hematológicas foram realizadas, assim como a peroxidação lipídica e atividade antioxidante. A atividade da ALT foi reduzida nos grupos tratados com metformina e TOL (200 mg/kg) quando comparada ao grupo controle e um aumento da ureia foi observado no grupo tratado com TOL (200 mg/kg) em comparação ao controle. O tratamento com TOL melhorou os níveis dos marcadores inflamatórios (IL-6, IL-10, TNF-α e IFN-γ) e das adipocinas (leptina, adiponectina e resistina) quando comparados aos animais diabéticos. Não houve diferença significativa nos níveis de MDA, bem como nenhuma alteração foi observada nas atividades antioxidante. Esses resultados indicam que a exposição à uma única ou repetidas doses não induziu toxicidade e uma potencial atividade anti-diabética da tintura das folhas de oliva, porém mais estudos são necessários para validar seus efeitos clínicos e sua segurança para uso em humanos.Universidade Federal de Santa MariaBrasilFarmacologiaUFSMPrograma de Pós-Graduação em FarmacologiaCentro de Ciências da SaúdeBauermann, Liliane de Freitashttp://lattes.cnpq.br/5849925846135968Lopes, Gilberti Helena Hübscherhttp://lattes.cnpq.br/1172295109796807Pavanato, Maria Amáliahttp://lattes.cnpq.br/8701892865724171Machado, Michel Mansurhttp://lattes.cnpq.br/7651341120825287Guex, Camille Gaube2020-12-16T13:12:57Z2020-12-16T13:12:57Z2016-03-04info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/20222ark:/26339/001300000g520porAttribution-NonCommercial-NoDerivatives 4.0 Internationalinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2022-06-27T14:57:17Zoai:repositorio.ufsm.br:1/20222Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/PUBhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.com||manancial@ufsm.bropendoar:2022-06-27T14:57:17Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.none.fl_str_mv Avaliação das toxicidades aguda e subaguda da Olea europaea L. e seu efeito no metabolismo de ratos diabéticos
Assessment of acute and subacute toxicities of Olea europaea L. and its effect in metabolism of diabetic rats
title Avaliação das toxicidades aguda e subaguda da Olea europaea L. e seu efeito no metabolismo de ratos diabéticos
spellingShingle Avaliação das toxicidades aguda e subaguda da Olea europaea L. e seu efeito no metabolismo de ratos diabéticos
Guex, Camille Gaube
Diabetes mellitus
Oliva
Folhas
Toxicidade
Olive
Leaves
Toxicity
CNPQ::CIENCIAS DA SAUDE::FARMACIA
title_short Avaliação das toxicidades aguda e subaguda da Olea europaea L. e seu efeito no metabolismo de ratos diabéticos
title_full Avaliação das toxicidades aguda e subaguda da Olea europaea L. e seu efeito no metabolismo de ratos diabéticos
title_fullStr Avaliação das toxicidades aguda e subaguda da Olea europaea L. e seu efeito no metabolismo de ratos diabéticos
title_full_unstemmed Avaliação das toxicidades aguda e subaguda da Olea europaea L. e seu efeito no metabolismo de ratos diabéticos
title_sort Avaliação das toxicidades aguda e subaguda da Olea europaea L. e seu efeito no metabolismo de ratos diabéticos
author Guex, Camille Gaube
author_facet Guex, Camille Gaube
author_role author
dc.contributor.none.fl_str_mv Bauermann, Liliane de Freitas
http://lattes.cnpq.br/5849925846135968
Lopes, Gilberti Helena Hübscher
http://lattes.cnpq.br/1172295109796807
Pavanato, Maria Amália
http://lattes.cnpq.br/8701892865724171
Machado, Michel Mansur
http://lattes.cnpq.br/7651341120825287
dc.contributor.author.fl_str_mv Guex, Camille Gaube
dc.subject.por.fl_str_mv Diabetes mellitus
Oliva
Folhas
Toxicidade
Olive
Leaves
Toxicity
CNPQ::CIENCIAS DA SAUDE::FARMACIA
topic Diabetes mellitus
Oliva
Folhas
Toxicidade
Olive
Leaves
Toxicity
CNPQ::CIENCIAS DA SAUDE::FARMACIA
description Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, insulin resistance and dyslipidemia. It is widely distributed worldwide, affecting millions of people and can lead to serious complications. Olive (Olea europaea L.) has important pharmacological activities, including antioxidant, anti-inflammatory and hypoglycemic. However, studies about its toxicity are still limited in the literature. Therefore, the aim of this study was to investigate the acute and subacute oral toxicities of the tincture of olive leaves (TOL) and evaluate the effect of TOL in metabolism of diabetic rats induced by high-fat diet and low dose of streptozotocin (STZ). In acute toxicity, a single dose of 2000 mg/kg of TOL was administered and observation was during 14 days, including behavior changes and signs of toxicity. In subacute study, TOL was administered for 28 days in the doses of 100, 200 and 400 mg/kg. Both treatments were by oral gavage in male and female rats and body weight was recorded. At the end of the experiment, blood was collected for biochemical and hematological analyses. The dose of 2000 mg /kg did not induce mortality or signs of toxicity. Animals exposed to repeated doses did not show abnormalities or hematological changes. At dose of 400 mg/kg, TOL increased levels of urea and reduced AST activity in males when compared to the different groups. Glucose levels decreased in males and females treated with TOL at different doses compared to controls. There was no significant change in body weight of animals in acute and subacute treatments. For the induction of experimental DM, animals were fed with a high-fat diet for 4 weeks and then was administered streptozotocin (35 mg/kg), via i.p., while the control group received regular diet and only citrate buffer via i.p. Rats with glucose levels above 200 mg/dL were considered diabetic. The animals were divided into 5 groups: Group I. negative control; Group II. diabetic treated with ethanol (51%); group III. diabetic treated with metformin (250 mg/kg) and groups IV and V. diabetic treated with TOL (200 mg/kg and 400 mg/kg, respectively). The administration was by oral gavage, daily, for 10 weeks. Hematologic and biochemical analyses were performed, as well as lipid peroxidation and antioxidant activity. The ALT activity was reduced in the groups treated with metformin and TOL (200 mg/kg) when compared to the control group and an increase in urea was observed in the group treated with TOL (200 mg/kg) compared to the control group. Treatment with TOL improved the levels of inflammatory markers (IL-6, IL-10, TNF-α and INF-γ) and adipokines (leptin, adiponectin and resistin) when compared to diabetic animals. There was no significant difference in MDA levels and no changes were observed in antioxidant activities. These results indicate that the exposure to a single or repeated doses did not induce toxicity and a potential anti-diabetic activity of tincture of olive leaves, but more studies are needed to validate its clinical effects and its safety for use in humans.
publishDate 2016
dc.date.none.fl_str_mv 2016-03-04
2020-12-16T13:12:57Z
2020-12-16T13:12:57Z
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dc.identifier.uri.fl_str_mv http://repositorio.ufsm.br/handle/1/20222
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identifier_str_mv ark:/26339/001300000g520
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language por
dc.rights.driver.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Santa Maria
Brasil
Farmacologia
UFSM
Programa de Pós-Graduação em Farmacologia
Centro de Ciências da Saúde
publisher.none.fl_str_mv Universidade Federal de Santa Maria
Brasil
Farmacologia
UFSM
Programa de Pós-Graduação em Farmacologia
Centro de Ciências da Saúde
dc.source.none.fl_str_mv reponame:Manancial - Repositório Digital da UFSM
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