<i>N</i>-Acetylcysteine Reduced Ischemia and Reperfusion Damage Associated with Steatohepatitis in Mice

<i>N</i>-acetylcysteine (NAC) is a pharmacological alternative with great potential for reducing the deleterious effects of surgical procedures on patients with steatohepatitis. We evaluated the effect of NAC on hepatic ischemia/reperfusion (I/R) injury in C57BL/6J mice, 8 weeks-old, wei...

Full description

Bibliographic Details
Main Authors: Natalie Chaves Cayuela, Marcia Kiyomi Koike, Jacqueline de Fátima Jacysyn, Roberto Rasslan, Anderson Romério Azevedo Cerqueira, Soraia Katia Pereira Costa, José Antônio Picanço Diniz-Júnior, Edivaldo Massazo Utiyama, Edna Frasson de Souza Montero
Format: Article
Language:English
Published: MDPI AG 2020-06-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/11/4106
id doaj-4305b45f2b3b43b68a7c3d5a37a9e69b
record_format Article
spelling doaj-4305b45f2b3b43b68a7c3d5a37a9e69b2020-11-25T03:34:21ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-01214106410610.3390/ijms21114106<i>N</i>-Acetylcysteine Reduced Ischemia and Reperfusion Damage Associated with Steatohepatitis in MiceNatalie Chaves Cayuela0Marcia Kiyomi Koike1Jacqueline de Fátima Jacysyn2Roberto Rasslan3Anderson Romério Azevedo Cerqueira4Soraia Katia Pereira Costa5José Antônio Picanço Diniz-Júnior6Edivaldo Massazo Utiyama7Edna Frasson de Souza Montero8Laboratory of Surgical Physiopathology—LIM-08, Department of Surgery, Faculdade de Medicina da Universidade de São Paulo (FMUSP), 01246-903 São Paulo, SP, BrazilDepartment of Emergency Medicine—LIM-51, FMUSP, 01246-903 São Paulo, SP, BrazilLaboratory of Surgical Physiopathology—LIM-08, Department of Surgery, Faculdade de Medicina da Universidade de São Paulo (FMUSP), 01246-903 São Paulo, SP, BrazilLaboratory of Surgical Physiopathology—LIM-08, Department of Surgery, Faculdade de Medicina da Universidade de São Paulo (FMUSP), 01246-903 São Paulo, SP, BrazilDepartmento de Farmacologia, Instituto de Ciêncas Biomédicas, Universidade de São Paulo (USP), 05508-900 São Paulo, SP, BrazilDepartmento de Farmacologia, Instituto de Ciêncas Biomédicas, Universidade de São Paulo (USP), 05508-900 São Paulo, SP, BrazilElectron Microscopy Laboratory, Section of Hepatology, Instituto Evandro Chagas, 66093-020 Belém, PA, BrazilLaboratory of Surgical Physiopathology—LIM-08, Department of Surgery, Faculdade de Medicina da Universidade de São Paulo (FMUSP), 01246-903 São Paulo, SP, BrazilLaboratory of Surgical Physiopathology—LIM-08, Department of Surgery, Faculdade de Medicina da Universidade de São Paulo (FMUSP), 01246-903 São Paulo, SP, Brazil<i>N</i>-acetylcysteine (NAC) is a pharmacological alternative with great potential for reducing the deleterious effects of surgical procedures on patients with steatohepatitis. We evaluated the effect of NAC on hepatic ischemia/reperfusion (I/R) injury in C57BL/6J mice, 8 weeks-old, weighing 25–30 g, with steatohepatitis induced by a methionine- and choline-deficient (MCD) diet. Groups: MCD group (steatohepatitis), MCD-I/R group (steatohepatitis plus 30 min of 70% liver ischemia and 24 h of reperfusion), MCD-I/R+NAC group (same as MCD-I/R group plus 150 mg/kg NAC 15 min before ischemia), and control group (normal AIN-93M diet). Liver enzymes and histopathology; nitrite and TBARS (thiobarbituric acid reactive substances) levels; pro-inflammatory cytokines; antioxidants enzymes; Nrf2 (nuclear factor erythroid-2-related factor 2) expression; and apoptosis were evaluated. In the group treated with NAC, reductions in inflammatory infiltration; AST (aspartate aminotransferase), nitrite, and TBARS levels; GPx (gutathione peroxidase) activity; cytokines synthesis; and number of apoptotic cells were observed while the GR (glutathione reductase) activity was increased. No differences were observed in Nfr2 expression or in SOD (superoxide dismutase), CAT (catalase), and GST (glutathione S-transferase) activities. Thus, it may be concluded that NAC exerts beneficial effects on mice livers with steatohepatitis submitted to I/R by reducing oxidative stress, inflammatory response, and cell death.https://www.mdpi.com/1422-0067/21/11/4106livermousesteatohepatitiscytokinesoxidative stressantioxidant enzymes
collection DOAJ
language English
format Article
sources DOAJ
author Natalie Chaves Cayuela
Marcia Kiyomi Koike
Jacqueline de Fátima Jacysyn
Roberto Rasslan
Anderson Romério Azevedo Cerqueira
Soraia Katia Pereira Costa
José Antônio Picanço Diniz-Júnior
Edivaldo Massazo Utiyama
Edna Frasson de Souza Montero
spellingShingle Natalie Chaves Cayuela
Marcia Kiyomi Koike
Jacqueline de Fátima Jacysyn
Roberto Rasslan
Anderson Romério Azevedo Cerqueira
Soraia Katia Pereira Costa
José Antônio Picanço Diniz-Júnior
Edivaldo Massazo Utiyama
Edna Frasson de Souza Montero
<i>N</i>-Acetylcysteine Reduced Ischemia and Reperfusion Damage Associated with Steatohepatitis in Mice
International Journal of Molecular Sciences
liver
mouse
steatohepatitis
cytokines
oxidative stress
antioxidant enzymes
author_facet Natalie Chaves Cayuela
Marcia Kiyomi Koike
Jacqueline de Fátima Jacysyn
Roberto Rasslan
Anderson Romério Azevedo Cerqueira
Soraia Katia Pereira Costa
José Antônio Picanço Diniz-Júnior
Edivaldo Massazo Utiyama
Edna Frasson de Souza Montero
author_sort Natalie Chaves Cayuela
title <i>N</i>-Acetylcysteine Reduced Ischemia and Reperfusion Damage Associated with Steatohepatitis in Mice
title_short <i>N</i>-Acetylcysteine Reduced Ischemia and Reperfusion Damage Associated with Steatohepatitis in Mice
title_full <i>N</i>-Acetylcysteine Reduced Ischemia and Reperfusion Damage Associated with Steatohepatitis in Mice
title_fullStr <i>N</i>-Acetylcysteine Reduced Ischemia and Reperfusion Damage Associated with Steatohepatitis in Mice
title_full_unstemmed <i>N</i>-Acetylcysteine Reduced Ischemia and Reperfusion Damage Associated with Steatohepatitis in Mice
title_sort <i>n</i>-acetylcysteine reduced ischemia and reperfusion damage associated with steatohepatitis in mice
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1661-6596
1422-0067
publishDate 2020-06-01
description <i>N</i>-acetylcysteine (NAC) is a pharmacological alternative with great potential for reducing the deleterious effects of surgical procedures on patients with steatohepatitis. We evaluated the effect of NAC on hepatic ischemia/reperfusion (I/R) injury in C57BL/6J mice, 8 weeks-old, weighing 25–30 g, with steatohepatitis induced by a methionine- and choline-deficient (MCD) diet. Groups: MCD group (steatohepatitis), MCD-I/R group (steatohepatitis plus 30 min of 70% liver ischemia and 24 h of reperfusion), MCD-I/R+NAC group (same as MCD-I/R group plus 150 mg/kg NAC 15 min before ischemia), and control group (normal AIN-93M diet). Liver enzymes and histopathology; nitrite and TBARS (thiobarbituric acid reactive substances) levels; pro-inflammatory cytokines; antioxidants enzymes; Nrf2 (nuclear factor erythroid-2-related factor 2) expression; and apoptosis were evaluated. In the group treated with NAC, reductions in inflammatory infiltration; AST (aspartate aminotransferase), nitrite, and TBARS levels; GPx (gutathione peroxidase) activity; cytokines synthesis; and number of apoptotic cells were observed while the GR (glutathione reductase) activity was increased. No differences were observed in Nfr2 expression or in SOD (superoxide dismutase), CAT (catalase), and GST (glutathione S-transferase) activities. Thus, it may be concluded that NAC exerts beneficial effects on mice livers with steatohepatitis submitted to I/R by reducing oxidative stress, inflammatory response, and cell death.
topic liver
mouse
steatohepatitis
cytokines
oxidative stress
antioxidant enzymes
url https://www.mdpi.com/1422-0067/21/11/4106
work_keys_str_mv AT nataliechavescayuela iniacetylcysteinereducedischemiaandreperfusiondamageassociatedwithsteatohepatitisinmice
AT marciakiyomikoike iniacetylcysteinereducedischemiaandreperfusiondamageassociatedwithsteatohepatitisinmice
AT jacquelinedefatimajacysyn iniacetylcysteinereducedischemiaandreperfusiondamageassociatedwithsteatohepatitisinmice
AT robertorasslan iniacetylcysteinereducedischemiaandreperfusiondamageassociatedwithsteatohepatitisinmice
AT andersonromerioazevedocerqueira iniacetylcysteinereducedischemiaandreperfusiondamageassociatedwithsteatohepatitisinmice
AT soraiakatiapereiracosta iniacetylcysteinereducedischemiaandreperfusiondamageassociatedwithsteatohepatitisinmice
AT joseantoniopicancodinizjunior iniacetylcysteinereducedischemiaandreperfusiondamageassociatedwithsteatohepatitisinmice
AT edivaldomassazoutiyama iniacetylcysteinereducedischemiaandreperfusiondamageassociatedwithsteatohepatitisinmice
AT ednafrassondesouzamontero iniacetylcysteinereducedischemiaandreperfusiondamageassociatedwithsteatohepatitisinmice
_version_ 1724559299958538240