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Recovery from Liver Failure and Fibrosis in a Rat Portacaval Anastomosis Model after Neurointermediate Pituitary Lobectomy

Liver diseases, including cirrhosis, viral hepatitis, and hepatocellular carcinoma, account for approximately two million annual deaths worldwide. They place a huge burden on the global healthcare systems, compelling researchers to find effective treatment for liver fibrosis-cirrhosis. Portacaval an...

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Autores principales: Muñoz-Ortega, Martín, Macías-Segura, Noé, Ventura-Juárez, Javier, Ávila-Blanco, Manuel Enrique, Ponce-Damian, Leonardo D., González-Blas, Daniel, Sánchez-Alemán, Esperanza, Quintanar-Stephano, Andrés
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677405/
https://www.ncbi.nlm.nih.gov/pubmed/34926704
http://dx.doi.org/10.1155/2021/5529784
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author Muñoz-Ortega, Martín
Macías-Segura, Noé
Ventura-Juárez, Javier
Ávila-Blanco, Manuel Enrique
Ponce-Damian, Leonardo D.
González-Blas, Daniel
Sánchez-Alemán, Esperanza
Quintanar-Stephano, Andrés
author_facet Muñoz-Ortega, Martín
Macías-Segura, Noé
Ventura-Juárez, Javier
Ávila-Blanco, Manuel Enrique
Ponce-Damian, Leonardo D.
González-Blas, Daniel
Sánchez-Alemán, Esperanza
Quintanar-Stephano, Andrés
author_sort Muñoz-Ortega, Martín
collection PubMed
description Liver diseases, including cirrhosis, viral hepatitis, and hepatocellular carcinoma, account for approximately two million annual deaths worldwide. They place a huge burden on the global healthcare systems, compelling researchers to find effective treatment for liver fibrosis-cirrhosis. Portacaval anastomosis (PCA) is a model of liver damage and fibrosis. Arginine vasopressin (AVP) has been implicated as a proinflammatory-profibrotic hormone. In rats, neurointermediate pituitary lobectomy (NIL) induces a permanent drop (80%) in AVP serum levels. We hypothesized that AVP deficiency (NIL-induced) may decrease liver damage and fibrosis in a rat PCA model. Male Wistar rats were divided into intact control (IC), NIL, PCA, and PCA+NIL groups. Liver function tests, liver gene relative expressions (IL-1, IL-10, TGF-β, COLL-I, MMP-9, and MMP-13), and histopathological assessments were performed. In comparison with those in the IC and PCA groups, bilirubin, protein serum, and liver glycogen levels were restored in the PCA+NIL group. NIL in the PCA animals also decreased the gene expression levels of IL-1 and COLL-I, while increasing those of IL-10, TGF-β, and MMP-13. Histopathology of this group also showed significantly decreased signs of liver damage with lower extent of collagen deposition and fibrosis. Low AVP serum levels were not enough to fully activate the AVP receptors resulting in the decreased activation of cell signaling pathways associated with proinflammatory-profibrotic responses, while activating cell molecular signaling pathways associated with an anti-inflammatory-fibrotic state. Thus, partial reversion of liver damage and fibrosis was observed. The study supports the crucial role of AVP in the inflammatory-fibrotic processes and maintenance of immune competence. The success of the AVP deficiency strategy suggests that blocking AVP receptors may be therapeutically useful to treat inflammatory-fibrotic liver diseases.
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spelling pubmed-86774052021-12-17 Recovery from Liver Failure and Fibrosis in a Rat Portacaval Anastomosis Model after Neurointermediate Pituitary Lobectomy Muñoz-Ortega, Martín Macías-Segura, Noé Ventura-Juárez, Javier Ávila-Blanco, Manuel Enrique Ponce-Damian, Leonardo D. González-Blas, Daniel Sánchez-Alemán, Esperanza Quintanar-Stephano, Andrés J Immunol Res Research Article Liver diseases, including cirrhosis, viral hepatitis, and hepatocellular carcinoma, account for approximately two million annual deaths worldwide. They place a huge burden on the global healthcare systems, compelling researchers to find effective treatment for liver fibrosis-cirrhosis. Portacaval anastomosis (PCA) is a model of liver damage and fibrosis. Arginine vasopressin (AVP) has been implicated as a proinflammatory-profibrotic hormone. In rats, neurointermediate pituitary lobectomy (NIL) induces a permanent drop (80%) in AVP serum levels. We hypothesized that AVP deficiency (NIL-induced) may decrease liver damage and fibrosis in a rat PCA model. Male Wistar rats were divided into intact control (IC), NIL, PCA, and PCA+NIL groups. Liver function tests, liver gene relative expressions (IL-1, IL-10, TGF-β, COLL-I, MMP-9, and MMP-13), and histopathological assessments were performed. In comparison with those in the IC and PCA groups, bilirubin, protein serum, and liver glycogen levels were restored in the PCA+NIL group. NIL in the PCA animals also decreased the gene expression levels of IL-1 and COLL-I, while increasing those of IL-10, TGF-β, and MMP-13. Histopathology of this group also showed significantly decreased signs of liver damage with lower extent of collagen deposition and fibrosis. Low AVP serum levels were not enough to fully activate the AVP receptors resulting in the decreased activation of cell signaling pathways associated with proinflammatory-profibrotic responses, while activating cell molecular signaling pathways associated with an anti-inflammatory-fibrotic state. Thus, partial reversion of liver damage and fibrosis was observed. The study supports the crucial role of AVP in the inflammatory-fibrotic processes and maintenance of immune competence. The success of the AVP deficiency strategy suggests that blocking AVP receptors may be therapeutically useful to treat inflammatory-fibrotic liver diseases. Hindawi 2021-12-09 /pmc/articles/PMC8677405/ /pubmed/34926704 http://dx.doi.org/10.1155/2021/5529784 Text en Copyright © 2021 Martín Muñoz-Ortega et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Muñoz-Ortega, Martín
Macías-Segura, Noé
Ventura-Juárez, Javier
Ávila-Blanco, Manuel Enrique
Ponce-Damian, Leonardo D.
González-Blas, Daniel
Sánchez-Alemán, Esperanza
Quintanar-Stephano, Andrés
Recovery from Liver Failure and Fibrosis in a Rat Portacaval Anastomosis Model after Neurointermediate Pituitary Lobectomy
title Recovery from Liver Failure and Fibrosis in a Rat Portacaval Anastomosis Model after Neurointermediate Pituitary Lobectomy
title_full Recovery from Liver Failure and Fibrosis in a Rat Portacaval Anastomosis Model after Neurointermediate Pituitary Lobectomy
title_fullStr Recovery from Liver Failure and Fibrosis in a Rat Portacaval Anastomosis Model after Neurointermediate Pituitary Lobectomy
title_full_unstemmed Recovery from Liver Failure and Fibrosis in a Rat Portacaval Anastomosis Model after Neurointermediate Pituitary Lobectomy
title_short Recovery from Liver Failure and Fibrosis in a Rat Portacaval Anastomosis Model after Neurointermediate Pituitary Lobectomy
title_sort recovery from liver failure and fibrosis in a rat portacaval anastomosis model after neurointermediate pituitary lobectomy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677405/
https://www.ncbi.nlm.nih.gov/pubmed/34926704
http://dx.doi.org/10.1155/2021/5529784
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