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

Aim 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...

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Principais autores: Araújo, Aurigena Antunes de, Araújo Júnior, Raimundo Fernandes de, Garcia, Vinícius Barreto, Leitão, Renata Ferreira de Carvalho, Brito, Gerly Anne de Castro, Miguel, Emilio de Castro, Guedes, Paulo Marcos Matta
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Idioma:eng
Publicado em: University of Navarra School of Medicine and Center for Applied Medical Research (CIMA), SPAIN
Assuntos:
Hepatic Stellate Cells
Carvedilol
Regulating Kuppfer Cells
Endereço do item:https://repositorio.ufrn.br/jspui/handle/123456789/25434
https://doi.org/10.1371/journal.pone.0148868
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spelling ri-123456789-254342021-11-11T18:17:52Z Carvedilol Improves Inflammatory Response, Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cells Araújo, Aurigena Antunes de Araújo Júnior, Raimundo Fernandes de Garcia, Vinícius Barreto Leitão, Renata Ferreira de Carvalho Brito, Gerly Anne de Castro Miguel, Emilio de Castro Guedes, Paulo Marcos Matta Hepatic Stellate Cells Carvedilol Regulating Kuppfer Cells Aim 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. 2018-06-16T15:33:59Z 2018-06-16T15:33:59Z 2016-02-18 article ARAÚJO, 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. 1932-6203 https://repositorio.ufrn.br/jspui/handle/123456789/25434 https://doi.org/10.1371/journal.pone.0148868 eng Acesso Aberto application/pdf University of Navarra School of Medicine and Center for Applied Medical Research (CIMA), SPAIN
institution Repositório Institucional
collection RI - UFRN
language eng
topic Hepatic Stellate Cells
Carvedilol
Regulating Kuppfer Cells
spellingShingle Hepatic Stellate Cells
Carvedilol
Regulating Kuppfer Cells
Araújo, Aurigena Antunes de
Araújo Júnior, Raimundo Fernandes de
Garcia, Vinícius Barreto
Leitão, Renata Ferreira de Carvalho
Brito, Gerly Anne de Castro
Miguel, Emilio de Castro
Guedes, Paulo Marcos Matta
Carvedilol Improves Inflammatory Response, Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cells
description Aim 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.
format article
author Araújo, Aurigena Antunes de
Araújo Júnior, Raimundo Fernandes de
Garcia, Vinícius Barreto
Leitão, Renata Ferreira de Carvalho
Brito, Gerly Anne de Castro
Miguel, Emilio de Castro
Guedes, Paulo Marcos Matta
author_facet Araújo, Aurigena Antunes de
Araújo Júnior, Raimundo Fernandes de
Garcia, Vinícius Barreto
Leitão, Renata Ferreira de Carvalho
Brito, Gerly Anne de Castro
Miguel, Emilio de Castro
Guedes, Paulo Marcos Matta
author_sort Araújo, Aurigena Antunes de
title Carvedilol Improves Inflammatory Response, Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cells
title_short Carvedilol Improves Inflammatory Response, Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cells
title_full Carvedilol Improves Inflammatory Response, Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cells
title_fullStr Carvedilol Improves Inflammatory Response, Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cells
title_full_unstemmed Carvedilol Improves Inflammatory Response, Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cells
title_sort carvedilol improves inflammatory response, oxidative stress and fibrosis in the alcohol-induced liver injury in rats by regulating kuppfer cells and hepatic stellate cells
publisher University of Navarra School of Medicine and Center for Applied Medical Research (CIMA), SPAIN
publishDate 2018
url https://repositorio.ufrn.br/jspui/handle/123456789/25434
https://doi.org/10.1371/journal.pone.0148868
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