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Acute Liver Failure Induces Glial Reactivity, Oxidative Stress and Impairs Brain Energy Metabolism in Rats

Acute liver failure (ALF) implies a severe and rapid liver dysfunction that leads to impaired liver metabolism and hepatic encephalopathy (HE). Recent studies have suggested that several brain alterations such as astrocytic dysfunction and energy metabolism impairment may synergistically interact, p...

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Autores principales: Guazzelli, Pedro Arend, Cittolin-Santos, Giordano Fabricio, Meira-Martins, Leo Anderson, Grings, Mateus, Nonose, Yasmine, Lazzarotto, Gabriel S., Nogara, Daniela, da Silva, Jussemara S., Fontella, Fernanda U., Wajner, Moacir, Leipnitz, Guilhian, Souza, Diogo O., de Assis, Adriano Martimbianco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968792/
https://www.ncbi.nlm.nih.gov/pubmed/31998076
http://dx.doi.org/10.3389/fnmol.2019.00327
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author Guazzelli, Pedro Arend
Cittolin-Santos, Giordano Fabricio
Meira-Martins, Leo Anderson
Grings, Mateus
Nonose, Yasmine
Lazzarotto, Gabriel S.
Nogara, Daniela
da Silva, Jussemara S.
Fontella, Fernanda U.
Wajner, Moacir
Leipnitz, Guilhian
Souza, Diogo O.
de Assis, Adriano Martimbianco
author_facet Guazzelli, Pedro Arend
Cittolin-Santos, Giordano Fabricio
Meira-Martins, Leo Anderson
Grings, Mateus
Nonose, Yasmine
Lazzarotto, Gabriel S.
Nogara, Daniela
da Silva, Jussemara S.
Fontella, Fernanda U.
Wajner, Moacir
Leipnitz, Guilhian
Souza, Diogo O.
de Assis, Adriano Martimbianco
author_sort Guazzelli, Pedro Arend
collection PubMed
description Acute liver failure (ALF) implies a severe and rapid liver dysfunction that leads to impaired liver metabolism and hepatic encephalopathy (HE). Recent studies have suggested that several brain alterations such as astrocytic dysfunction and energy metabolism impairment may synergistically interact, playing a role in the development of HE. The purpose of the present study is to investigate early alterations in redox status, energy metabolism and astrocytic reactivity of rats submitted to ALF. Adult male Wistar rats were submitted either to subtotal hepatectomy (92% of liver mass) or sham operation to induce ALF. Twenty-four hours after the surgery, animals with ALF presented higher plasmatic levels of ammonia, lactate, ALT and AST and lower levels of glucose than the animals in the sham group. Animals with ALF presented several astrocytic morphological alterations indicating astrocytic reactivity. The ALF group also presented higher mitochondrial oxygen consumption, higher enzymatic activity and higher ATP levels in the brain (frontoparietal cortex). Moreover, ALF induced an increase in glutamate oxidation concomitant with a decrease in glucose and lactate oxidation. The increase in brain energy metabolism caused by astrocytic reactivity resulted in augmented levels of reactive oxygen species (ROS) and Poly [ADP-ribose] polymerase 1 (PARP1) and a decreased activity of the enzymes superoxide dismutase and glutathione peroxidase (GSH-Px). These findings suggest that in the early stages of ALF the brain presents a hypermetabolic state, oxidative stress and astrocytic reactivity, which could be in part sustained by an increase in mitochondrial oxidation of glutamate.
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spelling pubmed-69687922020-01-29 Acute Liver Failure Induces Glial Reactivity, Oxidative Stress and Impairs Brain Energy Metabolism in Rats Guazzelli, Pedro Arend Cittolin-Santos, Giordano Fabricio Meira-Martins, Leo Anderson Grings, Mateus Nonose, Yasmine Lazzarotto, Gabriel S. Nogara, Daniela da Silva, Jussemara S. Fontella, Fernanda U. Wajner, Moacir Leipnitz, Guilhian Souza, Diogo O. de Assis, Adriano Martimbianco Front Mol Neurosci Neuroscience Acute liver failure (ALF) implies a severe and rapid liver dysfunction that leads to impaired liver metabolism and hepatic encephalopathy (HE). Recent studies have suggested that several brain alterations such as astrocytic dysfunction and energy metabolism impairment may synergistically interact, playing a role in the development of HE. The purpose of the present study is to investigate early alterations in redox status, energy metabolism and astrocytic reactivity of rats submitted to ALF. Adult male Wistar rats were submitted either to subtotal hepatectomy (92% of liver mass) or sham operation to induce ALF. Twenty-four hours after the surgery, animals with ALF presented higher plasmatic levels of ammonia, lactate, ALT and AST and lower levels of glucose than the animals in the sham group. Animals with ALF presented several astrocytic morphological alterations indicating astrocytic reactivity. The ALF group also presented higher mitochondrial oxygen consumption, higher enzymatic activity and higher ATP levels in the brain (frontoparietal cortex). Moreover, ALF induced an increase in glutamate oxidation concomitant with a decrease in glucose and lactate oxidation. The increase in brain energy metabolism caused by astrocytic reactivity resulted in augmented levels of reactive oxygen species (ROS) and Poly [ADP-ribose] polymerase 1 (PARP1) and a decreased activity of the enzymes superoxide dismutase and glutathione peroxidase (GSH-Px). These findings suggest that in the early stages of ALF the brain presents a hypermetabolic state, oxidative stress and astrocytic reactivity, which could be in part sustained by an increase in mitochondrial oxidation of glutamate. Frontiers Media S.A. 2020-01-10 /pmc/articles/PMC6968792/ /pubmed/31998076 http://dx.doi.org/10.3389/fnmol.2019.00327 Text en Copyright © 2020 Guazzeli, Cittolin-Santos, Meira-Martins, Grings, Nonose, Lazzarotto, Nogara, da Silva, Fontella, Wajner, Leipnitz, Souza and de Assis. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Guazzelli, Pedro Arend
Cittolin-Santos, Giordano Fabricio
Meira-Martins, Leo Anderson
Grings, Mateus
Nonose, Yasmine
Lazzarotto, Gabriel S.
Nogara, Daniela
da Silva, Jussemara S.
Fontella, Fernanda U.
Wajner, Moacir
Leipnitz, Guilhian
Souza, Diogo O.
de Assis, Adriano Martimbianco
Acute Liver Failure Induces Glial Reactivity, Oxidative Stress and Impairs Brain Energy Metabolism in Rats
title Acute Liver Failure Induces Glial Reactivity, Oxidative Stress and Impairs Brain Energy Metabolism in Rats
title_full Acute Liver Failure Induces Glial Reactivity, Oxidative Stress and Impairs Brain Energy Metabolism in Rats
title_fullStr Acute Liver Failure Induces Glial Reactivity, Oxidative Stress and Impairs Brain Energy Metabolism in Rats
title_full_unstemmed Acute Liver Failure Induces Glial Reactivity, Oxidative Stress and Impairs Brain Energy Metabolism in Rats
title_short Acute Liver Failure Induces Glial Reactivity, Oxidative Stress and Impairs Brain Energy Metabolism in Rats
title_sort acute liver failure induces glial reactivity, oxidative stress and impairs brain energy metabolism in rats
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968792/
https://www.ncbi.nlm.nih.gov/pubmed/31998076
http://dx.doi.org/10.3389/fnmol.2019.00327
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