Avaliação da atividade gastroprotetora do farnesol em modelos animais
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFPB |
Texto Completo: | https://repositorio.ufpb.br/jspui/handle/123456789/29897 |
Resumo: | Farnesol is a product of natural origin, belonging to the class of sesquiterpenes, found in the essential oils of lemongrass (Cymbopogon citratus) and chamomile (Matricaria camomila), in citrus fruits and vegetables. Farnesol has antioxidant, anti-inflammatory, anxiolytic, antinociceptive, anti-obesity, antimicrobial, antitumor and antidiarrheal activities. However, there are no studies in the literature about its gastroprotective activity, which motivated the choice of this substance for this study. Thus, this work aimed to evaluate the non-clinical acute toxicity and the gastroprotective effect of farnesol in animal models. For this, a behavioral assessment was carried out, estimation of the 50% lethal dose (LD50), analysis of the gastroprotective effect with different models of acute induction by harmful agents (ethanol, stress, NSAIDs and pylorus ligation) at different doses and determination of the mechanisms of actions involved in this effect (antisecretory, cytoprotective, antioxidant and immunoregulatory). The results obtained suggest that farnesol has low toxicity, with an LD50 equal to or greater than 2,500 mg/kg according to OECD Guide No. 423. In the ethanol-induced ulcer protocol, farnesol (25, 50, 100 and 200 mg/kg, p.o.) showed a gastroprotective effect in 73%, 92%, 97% and 98%, respectively, reduced the ulcerative lesion index (ILU) (p < 0.001) compared to the control group (tween 80 5%). In injuries induced by strain and cold stress, farnesol at the same doses reduced the ILU (p < 0.001) by 29%, 38%, 54% and 54%, respectively, compared to the negative control. When inducing lesions with NSAIDs (piroxicam), farnesol (25, 50, 100 and 200 mg/kg, p.o.) reduced ILU by 10% (p < 0.05), 23%, 46% and 51% (p < 0.001) respectively, compared to the negative control. In the experimental protocol of pylorus ligation (gastric juice containment), farnesol (100 mg/kg, v.o. and i.d.) reduced ILU (p < 0.001) by oral and intraduodenal routes, did not change pH in both routes and on H+ concentration and volume of gastric juice orally. However, it reduced the concentration of H+, the volume of gastric juice in the intraduodenal route. Previous administration of NEM blockers (blocker of sulfhydryl groups), L-NAME (NO synthesis inhibitor) and glibenclamide (KATP channel blocker) and indomethacin (cyclooxygenase inhibitor) reduced the gastroprotection exerted by farnesol (p < 0.001), suggesting the participation of these pathways in their gastroprotective activity. Farnesol increased gastric mucus in stomach tissue, suggesting the participation of this pathway in its gastroprotective activity. Farnesol also showed antioxidant effects by increasing the concentration of GSH and SOD activity and reducing MDA levels and MPO activity, as well as demonstrating an immunomodulatory effect by reducing the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α and increase the anti-inflammatory cytokine IL-10. |
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Avaliação da atividade gastroprotetora do farnesol em modelos animaisFarnesolSesquiterpenosÚlcera pépticaToxicidadeGastroproteçãoSesquiterpenePeptic ulcerToxicityGastroprotectionCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAFarnesol is a product of natural origin, belonging to the class of sesquiterpenes, found in the essential oils of lemongrass (Cymbopogon citratus) and chamomile (Matricaria camomila), in citrus fruits and vegetables. Farnesol has antioxidant, anti-inflammatory, anxiolytic, antinociceptive, anti-obesity, antimicrobial, antitumor and antidiarrheal activities. However, there are no studies in the literature about its gastroprotective activity, which motivated the choice of this substance for this study. Thus, this work aimed to evaluate the non-clinical acute toxicity and the gastroprotective effect of farnesol in animal models. For this, a behavioral assessment was carried out, estimation of the 50% lethal dose (LD50), analysis of the gastroprotective effect with different models of acute induction by harmful agents (ethanol, stress, NSAIDs and pylorus ligation) at different doses and determination of the mechanisms of actions involved in this effect (antisecretory, cytoprotective, antioxidant and immunoregulatory). The results obtained suggest that farnesol has low toxicity, with an LD50 equal to or greater than 2,500 mg/kg according to OECD Guide No. 423. In the ethanol-induced ulcer protocol, farnesol (25, 50, 100 and 200 mg/kg, p.o.) showed a gastroprotective effect in 73%, 92%, 97% and 98%, respectively, reduced the ulcerative lesion index (ILU) (p < 0.001) compared to the control group (tween 80 5%). In injuries induced by strain and cold stress, farnesol at the same doses reduced the ILU (p < 0.001) by 29%, 38%, 54% and 54%, respectively, compared to the negative control. When inducing lesions with NSAIDs (piroxicam), farnesol (25, 50, 100 and 200 mg/kg, p.o.) reduced ILU by 10% (p < 0.05), 23%, 46% and 51% (p < 0.001) respectively, compared to the negative control. In the experimental protocol of pylorus ligation (gastric juice containment), farnesol (100 mg/kg, v.o. and i.d.) reduced ILU (p < 0.001) by oral and intraduodenal routes, did not change pH in both routes and on H+ concentration and volume of gastric juice orally. However, it reduced the concentration of H+, the volume of gastric juice in the intraduodenal route. Previous administration of NEM blockers (blocker of sulfhydryl groups), L-NAME (NO synthesis inhibitor) and glibenclamide (KATP channel blocker) and indomethacin (cyclooxygenase inhibitor) reduced the gastroprotection exerted by farnesol (p < 0.001), suggesting the participation of these pathways in their gastroprotective activity. Farnesol increased gastric mucus in stomach tissue, suggesting the participation of this pathway in its gastroprotective activity. Farnesol also showed antioxidant effects by increasing the concentration of GSH and SOD activity and reducing MDA levels and MPO activity, as well as demonstrating an immunomodulatory effect by reducing the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α and increase the anti-inflammatory cytokine IL-10.Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqCoordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESO farnesol é um produto de origem natural, pertencente à classe dos sesquiterpenos, sendo encontrado nos óleos essenciais do capim-limão (Cymbopogon citratus) e camomila (Matricharia camomila), em frutas cítricas e vegetais. O farnesol apresenta atividades antioxidante, anti-inflamatória, ansiolítica, antinociceptiva, anti-obesidade, antimicrobiana, antitumoral e antidiarreica. Entretanto, não existem estudos na literatura sobre sua atividade gastroprotetora, o que motivou a escolha dessa substância para esse estudo. Dessa forma, este trabalho teve como objetivo avaliar a toxicidade aguda não clínica e o efeito gastroprotetor do farnesol em modelos animais. Para isso foi realizada a avaliação comportamental, estimativa da dose letal 50% (DL50), análise do efeito gastroprotetor com diferentes modelos de indução aguda pelos agentes lesivos (etanol, estresse, AINEs e ligadura do piloro) em diferentes doses e determinação dos mecanismos de ação envolvidos nesse efeito (antisecretórios, citoprotetores, antioxidantes e imunorregulatórios). Os resultados obtidos sugerem que o farnesol possui baixa toxicidade, com DL50 igual ou superior a 2.500 mg/kg conforme o guia nº 423 da OECD. No protocolo de úlcera induzida com etanol, o farnesol (25, 50, 100 e 200 mg/kg, v.o.) apresentou efeito gastroprotetor em 73%, 92%, 97% e 98%, respectivamente, reduziu o índice de lesão ulcerativa (ILU) (p < 0,001) em comparação ao grupo controle (tween 80 5%). Nas lesões induzidas pelo estresse por contensão e frio, o farnesol nas mesmas doses, reduziu o ILU (p < 0,001) em 29%, 38%, 54% e 54%, respectivamente, em comparação com o controle negativo. Na indução das lesões com AINEs (piroxicam), o farnesol (25, 50, 100 e 200 mg/kg, v.o.) reduziu o ILU em 10% (p < 0,05), 23%, 46% e 51% (p < 0,001) respectivamente, em comparação ao controle negativo. No protocolo experimental de ligadura do piloro (contensão do suco gástrico), o farnesol (100 mg/kg, v.o. e i.d.) reduziu o ILU (p < 0,001) pela via oral e intraduodenal, não exerceu alterações no pH em ambas as vias e na concentração de H+ e volume do suco gástrico por via oral. Entretanto, reduziu a concentração de H+, o volume do suco gástrico na via intraduodenal. A administração prévia dos bloqueadores NEM (bloqueador dos grupamentos sulfidrílicos), L-NAME (inibidor da síntese de NO) e glibenclamida (bloqueador do canal KATP) e indometacina (inibidor da ciclo-oxigenase), reduziu a gastroproteção exercida pelo farnesol (p < 0,001), sugerindo a participação dessas vias na sua atividade gastroprotetora. O farnesol aumentou o muco gástrico no tecido estomacal sugerindo a participação dessa via na sua atividade gastroprotetora. O farnesol também apresentou efeitos antioxidantes ao aumentar a concentração de GSH e a atividade da SOD e reduzir os níveis de MDA e a atividade da MPO, como também, demonstrou efeito imunomodulador ao reduzir as citocinas pró-inflamatórias IL-1β, IL-6 e TNF-α e aumentar a citocina anti-inflamatória IL-10.Universidade Federal da ParaíbaBrasilFarmacologiaPrograma de Pós-Graduação em Produtos Naturais e Sintéticos BioativosUFPBBatista, Leônia Mariahttp://lattes.cnpq.br/0601720493634706Pessôa, Michelle Liz de Souza2024-03-22T10:55:25Z2023-08-162024-03-22T10:55:25Z2023-06-07info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesishttps://repositorio.ufpb.br/jspui/handle/123456789/29897porAttribution-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nd/3.0/br/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2024-03-23T06:03:24Zoai:repositorio.ufpb.br:123456789/29897Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2024-03-23T06:03:24Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false |
dc.title.none.fl_str_mv |
Avaliação da atividade gastroprotetora do farnesol em modelos animais |
title |
Avaliação da atividade gastroprotetora do farnesol em modelos animais |
spellingShingle |
Avaliação da atividade gastroprotetora do farnesol em modelos animais Pessôa, Michelle Liz de Souza Farnesol Sesquiterpenos Úlcera péptica Toxicidade Gastroproteção Sesquiterpene Peptic ulcer Toxicity Gastroprotection CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Avaliação da atividade gastroprotetora do farnesol em modelos animais |
title_full |
Avaliação da atividade gastroprotetora do farnesol em modelos animais |
title_fullStr |
Avaliação da atividade gastroprotetora do farnesol em modelos animais |
title_full_unstemmed |
Avaliação da atividade gastroprotetora do farnesol em modelos animais |
title_sort |
Avaliação da atividade gastroprotetora do farnesol em modelos animais |
author |
Pessôa, Michelle Liz de Souza |
author_facet |
Pessôa, Michelle Liz de Souza |
author_role |
author |
dc.contributor.none.fl_str_mv |
Batista, Leônia Maria http://lattes.cnpq.br/0601720493634706 |
dc.contributor.author.fl_str_mv |
Pessôa, Michelle Liz de Souza |
dc.subject.por.fl_str_mv |
Farnesol Sesquiterpenos Úlcera péptica Toxicidade Gastroproteção Sesquiterpene Peptic ulcer Toxicity Gastroprotection CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
topic |
Farnesol Sesquiterpenos Úlcera péptica Toxicidade Gastroproteção Sesquiterpene Peptic ulcer Toxicity Gastroprotection CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Farnesol is a product of natural origin, belonging to the class of sesquiterpenes, found in the essential oils of lemongrass (Cymbopogon citratus) and chamomile (Matricaria camomila), in citrus fruits and vegetables. Farnesol has antioxidant, anti-inflammatory, anxiolytic, antinociceptive, anti-obesity, antimicrobial, antitumor and antidiarrheal activities. However, there are no studies in the literature about its gastroprotective activity, which motivated the choice of this substance for this study. Thus, this work aimed to evaluate the non-clinical acute toxicity and the gastroprotective effect of farnesol in animal models. For this, a behavioral assessment was carried out, estimation of the 50% lethal dose (LD50), analysis of the gastroprotective effect with different models of acute induction by harmful agents (ethanol, stress, NSAIDs and pylorus ligation) at different doses and determination of the mechanisms of actions involved in this effect (antisecretory, cytoprotective, antioxidant and immunoregulatory). The results obtained suggest that farnesol has low toxicity, with an LD50 equal to or greater than 2,500 mg/kg according to OECD Guide No. 423. In the ethanol-induced ulcer protocol, farnesol (25, 50, 100 and 200 mg/kg, p.o.) showed a gastroprotective effect in 73%, 92%, 97% and 98%, respectively, reduced the ulcerative lesion index (ILU) (p < 0.001) compared to the control group (tween 80 5%). In injuries induced by strain and cold stress, farnesol at the same doses reduced the ILU (p < 0.001) by 29%, 38%, 54% and 54%, respectively, compared to the negative control. When inducing lesions with NSAIDs (piroxicam), farnesol (25, 50, 100 and 200 mg/kg, p.o.) reduced ILU by 10% (p < 0.05), 23%, 46% and 51% (p < 0.001) respectively, compared to the negative control. In the experimental protocol of pylorus ligation (gastric juice containment), farnesol (100 mg/kg, v.o. and i.d.) reduced ILU (p < 0.001) by oral and intraduodenal routes, did not change pH in both routes and on H+ concentration and volume of gastric juice orally. However, it reduced the concentration of H+, the volume of gastric juice in the intraduodenal route. Previous administration of NEM blockers (blocker of sulfhydryl groups), L-NAME (NO synthesis inhibitor) and glibenclamide (KATP channel blocker) and indomethacin (cyclooxygenase inhibitor) reduced the gastroprotection exerted by farnesol (p < 0.001), suggesting the participation of these pathways in their gastroprotective activity. Farnesol increased gastric mucus in stomach tissue, suggesting the participation of this pathway in its gastroprotective activity. Farnesol also showed antioxidant effects by increasing the concentration of GSH and SOD activity and reducing MDA levels and MPO activity, as well as demonstrating an immunomodulatory effect by reducing the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α and increase the anti-inflammatory cytokine IL-10. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-08-16 2023-06-07 2024-03-22T10:55:25Z 2024-03-22T10:55:25Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufpb.br/jspui/handle/123456789/29897 |
url |
https://repositorio.ufpb.br/jspui/handle/123456789/29897 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nd/3.0/br/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nd/3.0/br/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal da Paraíba Brasil Farmacologia Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos UFPB |
publisher.none.fl_str_mv |
Universidade Federal da Paraíba Brasil Farmacologia Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos UFPB |
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reponame:Biblioteca Digital de Teses e Dissertações da UFPB instname:Universidade Federal da Paraíba (UFPB) instacron:UFPB |
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Universidade Federal da Paraíba (UFPB) |
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UFPB |
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UFPB |
reponame_str |
Biblioteca Digital de Teses e Dissertações da UFPB |
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Biblioteca Digital de Teses e Dissertações da UFPB |
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Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB) |
repository.mail.fl_str_mv |
diretoria@ufpb.br|| diretoria@ufpb.br |
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