<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...
Main Authors: | , , , , , , , , |
---|---|
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 |