Acute liver failure induces glial reactivity, oxidative stress and impairs brain energy metabolism in rats
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/215278 |
Resumo: | 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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Guazzelli, Pedro ArendSantos, Giordano Fabricio CittolinMartins, Leo Anderson MeiraGrings, MateusNonose, YasmineLazzarotto, GabrielaNogara, Daniela AlbugeriSilva, Jussemara Souza daFontella, Fernanda UrruthWajner, MoacirLeipnitz, GuilhianSouza, Diogo Onofre Gomes deAssis, Adriano Martimbianco de2020-11-20T04:15:05Z20201662-5099http://hdl.handle.net/10183/215278001116745Acute 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.application/pdfengFrontiers in molecular neuroscience. Lausanne. Vol. 12 (Jan. 2020), 327, 14 p.Falência hepática agudaEncefalopatia hepáticaEspécies reativas de oxigênioAstrócitosEstresse oxidativoAmôniaAcute liver failureBrain energy metabolismHepatic encephalopathyRedox homeostasisMitochondriaGlial reactivityAcute liver failure induces glial reactivity, oxidative stress and impairs brain energy metabolism in ratsEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001116745.pdf.txt001116745.pdf.txtExtracted Texttext/plain72405http://www.lume.ufrgs.br/bitstream/10183/215278/2/001116745.pdf.txtc9601bb6ae0a6f4db14997a036d76ad5MD52ORIGINAL001116745.pdfTexto completo (inglês)application/pdf2134644http://www.lume.ufrgs.br/bitstream/10183/215278/1/001116745.pdffeb2116c23ebb5fe20ee13646ce3751dMD5110183/2152782020-11-21 05:25:28.521679oai:www.lume.ufrgs.br:10183/215278Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2020-11-21T07:25:28Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
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 |
spellingShingle |
Acute liver failure induces glial reactivity, oxidative stress and impairs brain energy metabolism in rats Guazzelli, Pedro Arend Falência hepática aguda Encefalopatia hepática Espécies reativas de oxigênio Astrócitos Estresse oxidativo Amônia Acute liver failure Brain energy metabolism Hepatic encephalopathy Redox homeostasis Mitochondria Glial reactivity |
title_short |
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_sort |
Acute liver failure induces glial reactivity, oxidative stress and impairs brain energy metabolism in rats |
author |
Guazzelli, Pedro Arend |
author_facet |
Guazzelli, Pedro Arend Santos, Giordano Fabricio Cittolin Martins, Leo Anderson Meira Grings, Mateus Nonose, Yasmine Lazzarotto, Gabriela Nogara, Daniela Albugeri Silva, Jussemara Souza da Fontella, Fernanda Urruth Wajner, Moacir Leipnitz, Guilhian Souza, Diogo Onofre Gomes de Assis, Adriano Martimbianco de |
author_role |
author |
author2 |
Santos, Giordano Fabricio Cittolin Martins, Leo Anderson Meira Grings, Mateus Nonose, Yasmine Lazzarotto, Gabriela Nogara, Daniela Albugeri Silva, Jussemara Souza da Fontella, Fernanda Urruth Wajner, Moacir Leipnitz, Guilhian Souza, Diogo Onofre Gomes de Assis, Adriano Martimbianco de |
author2_role |
author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Guazzelli, Pedro Arend Santos, Giordano Fabricio Cittolin Martins, Leo Anderson Meira Grings, Mateus Nonose, Yasmine Lazzarotto, Gabriela Nogara, Daniela Albugeri Silva, Jussemara Souza da Fontella, Fernanda Urruth Wajner, Moacir Leipnitz, Guilhian Souza, Diogo Onofre Gomes de Assis, Adriano Martimbianco de |
dc.subject.por.fl_str_mv |
Falência hepática aguda Encefalopatia hepática Espécies reativas de oxigênio Astrócitos Estresse oxidativo Amônia |
topic |
Falência hepática aguda Encefalopatia hepática Espécies reativas de oxigênio Astrócitos Estresse oxidativo Amônia Acute liver failure Brain energy metabolism Hepatic encephalopathy Redox homeostasis Mitochondria Glial reactivity |
dc.subject.eng.fl_str_mv |
Acute liver failure Brain energy metabolism Hepatic encephalopathy Redox homeostasis Mitochondria Glial reactivity |
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. |
publishDate |
2020 |
dc.date.accessioned.fl_str_mv |
2020-11-20T04:15:05Z |
dc.date.issued.fl_str_mv |
2020 |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/215278 |
dc.identifier.issn.pt_BR.fl_str_mv |
1662-5099 |
dc.identifier.nrb.pt_BR.fl_str_mv |
001116745 |
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1662-5099 001116745 |
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http://hdl.handle.net/10183/215278 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Frontiers in molecular neuroscience. Lausanne. Vol. 12 (Jan. 2020), 327, 14 p. |
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info:eu-repo/semantics/openAccess |
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openAccess |
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