Carvedilol Improves Inflammatory Response, Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cells

dc.contributor.authorAraújo, Aurigena Antunes de
dc.contributor.authorAraújo Júnior, Raimundo Fernandes de
dc.contributor.authorGarcia, Vinícius Barreto
dc.contributor.authorLeitão, Renata Ferreira de Carvalho
dc.contributor.authorBrito, Gerly Anne de Castro
dc.contributor.authorMiguel, Emilio de Castro
dc.contributor.authorGuedes, Paulo Marcos Matta
dc.date.accessioned2018-06-16T15:33:59Z
dc.date.available2018-06-16T15:33:59Z
dc.date.issued2016-02-18
dc.description.resumoAim To evaluate the anti-inflammatory, anti-oxidant and antifibrotic effects of carvedilol (CARV) in rats with ethanol-induced liver injury. Methods Liver injury was induced by gavage administration of alcohol (7 g/kg) for 28 consecutive days. Eighty Wistar rats were pretreated with oral CARV at 1, 3, or 5 mg/kg or with saline 1 h before exposure to alcohol. Liver homogenates were assayed for interleukin (IL)-1β, IL-10, and tumor necrosis factor (TNF)-α level as well as for myeloperoxidase (MPO) activity and malonyldialdehyde (MDA) and glutathione (GSH) levels. Serum aspartate aminotransferase (AST) activity and liver triglyceride (TG) levels were also assayed. Immunohistochemical analyses of cyclooxygenase 2 (COX-2), receptor activator of nuclear factor kappa-B/ligand (RANK/RANKL), suppressor of cytokine signalling (SOCS1), the Kupffer cell marker IBA-1 (ionized calcium-binding adaptor molecule 1), intercellular adhesion molecule 1 (ICAM-1), superoxide dismutase (SOD-1), and glutathione peroxidase (GPx-1) expression were performed. Confocal microscopy analysis of IL-1β and NF-κB expression and real-time quantitative PCR analysis for TNFα, PCI, PCIII, and NF-κB were performed. Results CARV treatment (5 mg/kg) during the alcohol exposure protocol was associated with reduced steatosis, hepatic cord degeneration, fibrosis and necrosis, as well as reduced levels of AST (p < 0.01), ALT (p < 0.01), TG (p < 0.001), MPO (p < 0.001), MDA (p < 0.05), and proinflammatory cytokines (IL-1β and TNF-α, both p < 0.05), and increased levels of the anti-inflammatory cytokine IL-10 (p < 0.001) and GSH (p < 0.05), compared to the alcohol-only group. Treatment with CARV 5 mg/kg also reduced expression levels of COX-2, RANK, RANKL, IBA-1, and ICAM-1 (all p < 0.05), while increasing expression of SOCS1, SOD-1, and GPx-1 (all p < 0.05) and decreasing expression of IL-1β and NF-κB (both, p < 0.05). Real-time quantitative PCR analysis showed that mRNA production of TNF-α, procollagen type I (PCI), procollagen type III (PCIII), and NF-κB were decreased in the alcohol-CARV 5 mg/kg group relative to the alcohol-only group. Conclusions CARV can reduce the stress oxidative, inflammatory response and fibrosis in ethanol-induced liver injury in a rat model by downregulating signalling of Kuppfer cells and hepatic stellate cells (HSCs) through suppression of inflammatory cytokines.pt_BR
dc.identifier.citationARAÚJO, Aurigena Antunes de et al. Carvedilol Improves Inflammatory Response, Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cells. Plos One, v. 11, p. e0148868, 2016. Disponível em: <http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0148868>. Acesso em: 20 mar. 2018.pt_BR
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0148868
dc.identifier.issn1932-6203
dc.identifier.urihttps://repositorio.ufrn.br/jspui/handle/123456789/25434
dc.languageengpt_BR
dc.publisherUniversity of Navarra School of Medicine and Center for Applied Medical Research (CIMA), SPAINpt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectHepatic Stellate Cellspt_BR
dc.subjectCarvedilolpt_BR
dc.subjectRegulating Kuppfer Cellspt_BR
dc.titleCarvedilol Improves Inflammatory Response, Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cellspt_BR
dc.typearticlept_BR

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