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Previous issue date: 2015-05-15 / Liver fibrosis is a complex disease that is caused by inappropriate tissue repair due to the deposition of connective tissue. When a chronic lesion affects the liver, regenerative response fails and hepatocytes are replaced with abundant extracellular matrix (ECM). The imbalance between production and degradation of ECM will result in the accumulation of proteins that change normal liver architecture, and thus its functionality. The main source of ECM is the activated hepatic stellate cell (HSC). In order, to clarify possible therapeutic approaches to the disease, the this work aimed to evaluate the possible antifibrotic action of Pluchea sagitallis (Lam.) Cabrera on an activated HSC immortalized lineage (GRX). Our results demonstrated that the P. sagittalis aqueous extract at 0.039 and 0.078 mg/mL concentrations was able to reduce cell growth and proliferation. Regarding to oxidative stress evaluation, there was no statistically significant difference between the treated group and the control. Staining with OilRed-O (ORO) showed a statistically significant increase in intracellular lipid content after 5 days of treatment, exerting in vitro effect on the GRX phenotypic change of activated towards the quiescent state. These results were confirmed by colorimetric quantification of lipid content. Regarding the TGF-?1 and collagen production, there were no statistically significant differences observed between the groups. In conclusion, the P. sagittalis aqueous extract reduces the growth and proliferation of GRX cells and induces the reversal of activated towards a quiescent phenotype. There was no decrease in cell proliferation either by necrosis or by apoptosis via activation of the senescence. Thus, our data suggest that the extract showed an antifibrotic effect, possibly by activating phenotype reversal. / A fibrose hep?tica apresenta uma patog?nese complexa causada por reparo tecidual inadequado devido ? deposi??o de tecido conectivo. Quando um dano cr?nico acomete o f?gado, a resposta regenerativa falha e os hepat?citos s?o substitu?dos por matriz extracelular (ECM) excedente. Assim, o desequil?brio entre a degrada??o e a produ??o de ECM acarretar? no ac?mulo dessas prote?nas que alteram a arquitetura normal do f?gado e, consequentemente, sua funcionalidade. A principal fonte de ECM ? a c?lula estrelada hep?tica (HSC) ativada. Sendo assim, na tentativa de elucidar poss?veis abordagens terap?uticas para a doen?a, o objetivo desse trabalho foi avaliar a poss?vel a??o antifibr?tica do extrato aquoso de Pluchea sagitallis (Lam.) Cabrera sobre uma linhagem imortalizada de HSC ativadas (GRX). Nossos resultados demonstraram que as concentra??es de 0,039 e 0,078 mg/mL do extrato aquoso de P. sagitallis foram capazes de diminuir o crescimento e a prolifera??o celular. Quanto ? avalia??o do estresse oxidativo, n?o foi observada diferen?a estatisticamente significativa entre o grupo tratado e controle. A colora??o com oil red (ORO) mostrou aumento significativo do conte?do lip?dico intracelular ap?s 5 dias de tratamento, indicando efeito in vitro sobre a mudan?a fenot?pica em linhagem GRX, do estado ativado para o estado quiescente. Esses resultados foram confirmados pela quantifica??o colorim?trica de lip?dios. Em rela??o ? produ??o de TGF-?1 e col?geno total, n?o foram observadas diferen?as estatisticamente significativas entre os grupos. Concluindo, o extrato aquoso da P. sagittalis diminuiu o crescimento e a prolifera??o das c?lulas GRX e induziu a revers?o do fen?tipo ativado para quiescente. A diminui??o na prolifera??o celular n?o ocorreu nem por necrose nem por ativa??o da apoptose e senesc?ncia. Sendo assim, nossos resultados sugerem que o extrato apresenta um efeito antifibr?tico, possivelmente pela via que ativa a revers?o do fen?tipo.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/6349 |
| Date | 15 May 2015 |
| Creators | Ouriques, Fabiana Garbachi de Oliveira Mendes |
| Contributors | Oliveira, Jarbas Rodrigues de |
| Publisher | Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Programa de P?s-Gradua??o em Biotecnologia Farmac?utica, PUCRS, Brasil, Faculdade de Farm?cia |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS, instname:Pontifícia Universidade Católica do Rio Grande do Sul, instacron:PUC_RS |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2304961219518893267, 600, 600, 600, -8380654636843378116, 6997636413449754996 |
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