Efeito protetor do sesquiterpenóide β-Ionona na lesão gástrica induzida por etanol em camundongos : envolvimento da via NO/GMPc/KATP e da glutationa

Detalhes bibliográficos
Autor(a) principal: Freitas, Lyara Barbosa Nogueira
Data de Publicação: 2013
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
Texto Completo: http://www.repositorio.ufc.br/handle/riufc/5691
Resumo: The β-ionone (4-[2,6,6-cyclohexene-1-trimetill]-3-butene-2-one) is a sesquiterpene (degraded terpenoid - C13) present in the molecular structure of retinol and β-carotene acid retinoic being formed from the mevalonate pathway in different types of plants. Research on the biological activities of β-ionone are still incipient and limited results with this compound are found in the literature. This study aims to investigate the activity of β-ionone in the model of ethanol-induced gastric injury. Handling of animals and experimental protocols were recorded by the Ethics Committee on Animal Research (CEPA) under number 87/2011. Swiss mice (n = 8), fasted 18 hours, were orally treated with BI at doses of 6.25, 12.5, 25, 50 and 100mg/kg. After 60 min of administration BI animals received 0.2 ml of absolute ethanol po. After 60 min this administration, the animals were sacrificed, the stomachs removed and analyzed to determine the rate of injury. Histologic examination of the stomach was performed by assigning scores to the parameters of edema, hemorrhage, loss of epithelial cells and inflammatory infiltrate. To investigate the role of mediators in BI effect, animals received indomethacin (10 mg / kg, po), L-NAME (20 mg / kg, ip) ODQ (10 mg / kg, ip), glibenclamide (5 mg / kg, ip) and capsazepine (5 mg / kg, ip) before treatment with BI (12.5 mg / kg, po). Misoprostol (50 mg / kg po), L-arginine (600 mg / kg, ip), diazoxide (3 mg / kg, ip) and capsaicin (0.3 mg / kg, po) was used positive pattern. The levels of nitrite and glutathione were measured in the stomach mucosa to investigate the effect of BI on the levels of NO and its antioxidant effect, respectively. Treatment of animals with the BI (12.5, 25, 50 and 100 mg / kg) reduced significantly and dose-dependent manner, the area of ethanol-induced gastric lesion to (11.41 ± 2.0, 7 92 * ± 1.8, 6.32 ± 2.0 and 1.43 ± 0.42% respectively). However, the BI lowest tested dose (6.25 mg / kg) showed no significant reduction of the ulcerated area (21.97 ± 1.8%). The administration of BI scores decreased hemorrhage, edema and loss of epithelial cells. The capsazepine and indomethacin were not able to reverse the protective effect of BI. Pretreatment of animals with L-NAME, ODQ and glibenclamide reversed the gastroprotective effect of BI, showing the involvement of NO and KATP channels in its mechanism of action. The group pretreated with BI (12.5 mg / kg po) showed a higher concentration of nitrite (24.18 mM) compared to the control group (17.68 mM). The pretreatment BI was effective in protecting against oxidative damage (346.4 ± 60.32 mg / g of tissue), preventing depletion of GSH levels in tissue. These results indicate that the β-ionone has gastroprotective effect in the model of ethanol-induced gastric injury mediated by the NO cGMP K ATP and terpene through the mediation of the GSH depletion induced by ethanol.
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spelling Efeito protetor do sesquiterpenóide β-Ionona na lesão gástrica induzida por etanol em camundongos : envolvimento da via NO/GMPc/KATP e da glutationaProtective effect of β-ionone sesquiterpenóide in ethanol-induced gastric injury in mice : involvement via NO / cGMP / KATP and glutathioneÚlcera GástricaEtanolGlutationaThe β-ionone (4-[2,6,6-cyclohexene-1-trimetill]-3-butene-2-one) is a sesquiterpene (degraded terpenoid - C13) present in the molecular structure of retinol and β-carotene acid retinoic being formed from the mevalonate pathway in different types of plants. Research on the biological activities of β-ionone are still incipient and limited results with this compound are found in the literature. This study aims to investigate the activity of β-ionone in the model of ethanol-induced gastric injury. Handling of animals and experimental protocols were recorded by the Ethics Committee on Animal Research (CEPA) under number 87/2011. Swiss mice (n = 8), fasted 18 hours, were orally treated with BI at doses of 6.25, 12.5, 25, 50 and 100mg/kg. After 60 min of administration BI animals received 0.2 ml of absolute ethanol po. After 60 min this administration, the animals were sacrificed, the stomachs removed and analyzed to determine the rate of injury. Histologic examination of the stomach was performed by assigning scores to the parameters of edema, hemorrhage, loss of epithelial cells and inflammatory infiltrate. To investigate the role of mediators in BI effect, animals received indomethacin (10 mg / kg, po), L-NAME (20 mg / kg, ip) ODQ (10 mg / kg, ip), glibenclamide (5 mg / kg, ip) and capsazepine (5 mg / kg, ip) before treatment with BI (12.5 mg / kg, po). Misoprostol (50 mg / kg po), L-arginine (600 mg / kg, ip), diazoxide (3 mg / kg, ip) and capsaicin (0.3 mg / kg, po) was used positive pattern. The levels of nitrite and glutathione were measured in the stomach mucosa to investigate the effect of BI on the levels of NO and its antioxidant effect, respectively. Treatment of animals with the BI (12.5, 25, 50 and 100 mg / kg) reduced significantly and dose-dependent manner, the area of ethanol-induced gastric lesion to (11.41 ± 2.0, 7 92 * ± 1.8, 6.32 ± 2.0 and 1.43 ± 0.42% respectively). However, the BI lowest tested dose (6.25 mg / kg) showed no significant reduction of the ulcerated area (21.97 ± 1.8%). The administration of BI scores decreased hemorrhage, edema and loss of epithelial cells. The capsazepine and indomethacin were not able to reverse the protective effect of BI. Pretreatment of animals with L-NAME, ODQ and glibenclamide reversed the gastroprotective effect of BI, showing the involvement of NO and KATP channels in its mechanism of action. The group pretreated with BI (12.5 mg / kg po) showed a higher concentration of nitrite (24.18 mM) compared to the control group (17.68 mM). The pretreatment BI was effective in protecting against oxidative damage (346.4 ± 60.32 mg / g of tissue), preventing depletion of GSH levels in tissue. These results indicate that the β-ionone has gastroprotective effect in the model of ethanol-induced gastric injury mediated by the NO cGMP K ATP and terpene through the mediation of the GSH depletion induced by ethanol.A β-ionona (4-[2,6,6-trimetill-1-ciclohexeno]-3-buten-2-ona) é um sesquiterpeno (terpenoide degradado - C13) presente na estrutura molecular do retinol, β-caroteno e ácido retinóico, sendo formado a partir da via do mevalonato em diferentes tipos de plantas. As pesquisas sobre as atividades biológicas da β-ionona ainda são incipientes e poucos resultados com este composto são encontrados na literatura. Este estudo visa investigar a atividade da β-ionona no modelo de lesão gástrica induzida por etanol. A manipulação dos animais e os protocolos experimentais foram registrados na Comissão de Ética em Pesquisa Animal (CEPA) sob o número 87/2011. Camundongos Swiss (n = 8), em jejum de 18 h, receberam, por gavagem, BI nas doses de 6,25; 12,5; 25; 50 e 100 mg/kg. Após 60 min da administração de BI os animais receberam 0,2 ml de etanol absoluto por gavagem. Decorridos 60 min dessa administração, os animais foram sacrificados, os estômagos removidos e analisados para determinação do índice de lesão. A avaliação histopatológica do estômago foi realizada atribuindo escores aos parâmetros de edema, hemorragia, perda de células epiteliais e infiltrado inflamatório. Para investigar o envolvimento de mediadores no efeito de BI, os animais receberam indometacina (10 mg/kg; v.o.), L-NAME (20 mg/kg; i.p.), ODQ (10 mg/kg; i.p.), glibenclamida (5 mg/kg; i.p.) e capsazepina (5 mg/kg; i.p) antes do tratamento com BI (12,5 mg/kg; v.o.). Misoprostol (50 µg/kg v.o), L-arginina (600 mg/kg; i.p.), diazóxido (3 mg/kg; i.p.) e capsaicina (0,3 mg/kg; v.o.) foram utilizados padrão positivo. Os níveis de nitrito e glutationa foram dosados na mucosa do estômago para investigar o efeito da BI sobre os níveis de NO e seu efeito antioxidante, respectivamente. O tratamento dos animais com a BI (12,5; 25; 50 e 100 mg/kg), reduziu significativamente e de forma dose-dependente, a área da lesão gástrica induzida pelo etanol para (11,41 ± 2,0; 7,92 ± 1,8*; 6,32 ± 2,0 e 1,43 ± 0,42 % respectivamente). Entretanto, a BI na menor dose avaliada (6,25 mg/kg), não apresentou redução significativa da área ulcerada (21,97 ± 1,8%). A administração de BI reduziu os escores de hemorragia, edema e a perda de células epiteliais. A Indometacina e capsazepina não foram capazes de reverter o efeito protetor da BI. O pré-tratamento dos animais com L-NAME, ODQ e Glibenclamida reverteu o efeito gastroprotetora da BI, mostrando o envolvimento do NO e canais KATP no seu mecanismo de ação. O grupo pré-tratado com BI (12,5 mg/kg v.o.) mostrou uma maior concentração de nitrito (24,18 mM) quando comparado ao grupo controle (17,68 mM). O pré tratamento com BI foi efetivo em proteger contra o dano oxidativo (346,4 ± 60,32 µg/g de tecido), evitando a depleção nos níveis de GSH no tecido. Estes resultados indicam que a β-ionona possui efeito gastroprotetor no modelo de Lesão Gástrica induzida por Etanol mediado pela via NOGMPcKATP e através da mediação do terpeno na depleção dos níveis de GSH provocado pelo etanol.Alencar, Nylane Maria Nunes deFreitas, Lyara Barbosa Nogueira2013-08-27T11:56:22Z2013-08-27T11:56:22Z2013info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfFREITAS, L. B. N. Efeito protetor do sesquiterpenóide ß-Ionona na lesão gástrica induzida por etanol em camundongos : envolvimento da via NO/GMPc/Katp e da glutationa. 2013. 84 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2013.http://www.repositorio.ufc.br/handle/riufc/5691porreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2019-10-23T16:28:43Zoai:repositorio.ufc.br:riufc/5691Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-09-11T18:34:33.370408Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.none.fl_str_mv Efeito protetor do sesquiterpenóide β-Ionona na lesão gástrica induzida por etanol em camundongos : envolvimento da via NO/GMPc/KATP e da glutationa
Protective effect of β-ionone sesquiterpenóide in ethanol-induced gastric injury in mice : involvement via NO / cGMP / KATP and glutathione
title Efeito protetor do sesquiterpenóide β-Ionona na lesão gástrica induzida por etanol em camundongos : envolvimento da via NO/GMPc/KATP e da glutationa
spellingShingle Efeito protetor do sesquiterpenóide β-Ionona na lesão gástrica induzida por etanol em camundongos : envolvimento da via NO/GMPc/KATP e da glutationa
Freitas, Lyara Barbosa Nogueira
Úlcera Gástrica
Etanol
Glutationa
title_short Efeito protetor do sesquiterpenóide β-Ionona na lesão gástrica induzida por etanol em camundongos : envolvimento da via NO/GMPc/KATP e da glutationa
title_full Efeito protetor do sesquiterpenóide β-Ionona na lesão gástrica induzida por etanol em camundongos : envolvimento da via NO/GMPc/KATP e da glutationa
title_fullStr Efeito protetor do sesquiterpenóide β-Ionona na lesão gástrica induzida por etanol em camundongos : envolvimento da via NO/GMPc/KATP e da glutationa
title_full_unstemmed Efeito protetor do sesquiterpenóide β-Ionona na lesão gástrica induzida por etanol em camundongos : envolvimento da via NO/GMPc/KATP e da glutationa
title_sort Efeito protetor do sesquiterpenóide β-Ionona na lesão gástrica induzida por etanol em camundongos : envolvimento da via NO/GMPc/KATP e da glutationa
author Freitas, Lyara Barbosa Nogueira
author_facet Freitas, Lyara Barbosa Nogueira
author_role author
dc.contributor.none.fl_str_mv Alencar, Nylane Maria Nunes de
dc.contributor.author.fl_str_mv Freitas, Lyara Barbosa Nogueira
dc.subject.por.fl_str_mv Úlcera Gástrica
Etanol
Glutationa
topic Úlcera Gástrica
Etanol
Glutationa
description The β-ionone (4-[2,6,6-cyclohexene-1-trimetill]-3-butene-2-one) is a sesquiterpene (degraded terpenoid - C13) present in the molecular structure of retinol and β-carotene acid retinoic being formed from the mevalonate pathway in different types of plants. Research on the biological activities of β-ionone are still incipient and limited results with this compound are found in the literature. This study aims to investigate the activity of β-ionone in the model of ethanol-induced gastric injury. Handling of animals and experimental protocols were recorded by the Ethics Committee on Animal Research (CEPA) under number 87/2011. Swiss mice (n = 8), fasted 18 hours, were orally treated with BI at doses of 6.25, 12.5, 25, 50 and 100mg/kg. After 60 min of administration BI animals received 0.2 ml of absolute ethanol po. After 60 min this administration, the animals were sacrificed, the stomachs removed and analyzed to determine the rate of injury. Histologic examination of the stomach was performed by assigning scores to the parameters of edema, hemorrhage, loss of epithelial cells and inflammatory infiltrate. To investigate the role of mediators in BI effect, animals received indomethacin (10 mg / kg, po), L-NAME (20 mg / kg, ip) ODQ (10 mg / kg, ip), glibenclamide (5 mg / kg, ip) and capsazepine (5 mg / kg, ip) before treatment with BI (12.5 mg / kg, po). Misoprostol (50 mg / kg po), L-arginine (600 mg / kg, ip), diazoxide (3 mg / kg, ip) and capsaicin (0.3 mg / kg, po) was used positive pattern. The levels of nitrite and glutathione were measured in the stomach mucosa to investigate the effect of BI on the levels of NO and its antioxidant effect, respectively. Treatment of animals with the BI (12.5, 25, 50 and 100 mg / kg) reduced significantly and dose-dependent manner, the area of ethanol-induced gastric lesion to (11.41 ± 2.0, 7 92 * ± 1.8, 6.32 ± 2.0 and 1.43 ± 0.42% respectively). However, the BI lowest tested dose (6.25 mg / kg) showed no significant reduction of the ulcerated area (21.97 ± 1.8%). The administration of BI scores decreased hemorrhage, edema and loss of epithelial cells. The capsazepine and indomethacin were not able to reverse the protective effect of BI. Pretreatment of animals with L-NAME, ODQ and glibenclamide reversed the gastroprotective effect of BI, showing the involvement of NO and KATP channels in its mechanism of action. The group pretreated with BI (12.5 mg / kg po) showed a higher concentration of nitrite (24.18 mM) compared to the control group (17.68 mM). The pretreatment BI was effective in protecting against oxidative damage (346.4 ± 60.32 mg / g of tissue), preventing depletion of GSH levels in tissue. These results indicate that the β-ionone has gastroprotective effect in the model of ethanol-induced gastric injury mediated by the NO cGMP K ATP and terpene through the mediation of the GSH depletion induced by ethanol.
publishDate 2013
dc.date.none.fl_str_mv 2013-08-27T11:56:22Z
2013-08-27T11:56:22Z
2013
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
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dc.identifier.uri.fl_str_mv FREITAS, L. B. N. Efeito protetor do sesquiterpenóide ß-Ionona na lesão gástrica induzida por etanol em camundongos : envolvimento da via NO/GMPc/Katp e da glutationa. 2013. 84 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2013.
http://www.repositorio.ufc.br/handle/riufc/5691
identifier_str_mv FREITAS, L. B. N. Efeito protetor do sesquiterpenóide ß-Ionona na lesão gástrica induzida por etanol em camundongos : envolvimento da via NO/GMPc/Katp e da glutationa. 2013. 84 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2013.
url http://www.repositorio.ufc.br/handle/riufc/5691
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