Liver glutathione depletion after preservation and reperfusion in human liver transplantation

PURPOSE: The oxidative stress is an important mechanism responsible for dysfunction after orthotopic liver transplantation (OLT). Glutathione (GSH) low levels after cold storage render the grafts vulnerable to reperfusion injury. Aim of this study was to evaluate GSH and oxidized glutathione (GSSG) liver concentrations, the hepatocellular injury and function in optimal and suboptimal grafts after human OLT. METHODS: Liver biopsies were taken in 33 patients before the implant and two hours after reperfusion, allowing determination of GSH, GSSG and oxidative stress ratio (GSH/GSSG). Serum transaminases, prothrombin activity (PT) and factor V were measured to evaluate injury and function respectively. Histopathological injury was analyzed by an index of five parameters. RESULTS: There was a decrease in GSH (p<0.01) after reperfusion (0.323 ± 0.062 ìmol/g to 0.095 ± 0.01 ìmol/g and 0.371 ± 0.052 ìmol/g to 0.183 ± 0.046 ìmol/g) in suboptimal and optimal groups, respectively. An increase of GSSG (p<0.05) occurred after reperfusion (0.172 ± 0.038 ìmol/g to 0.278 ± 0.077 ìmol/g and 0.229 ± 0.048 ìmol/g to 0.356 ± 0.105 ìmol/g) in suboptimal and optimal groups, respectively. A decrease (p<0.01) occurred in the GSH/GSSG ratio after reperfusion (2.23 ± 0.31 to 0.482 ± 0.042 and 2.47 ± 0.32 to 0.593 ± 0.068) in suboptimal and optimal groups, respectively. Histopathological injury scores were higher (p<0.05) in the suboptimal group than in optimal (6.46 ± 0.4 vs. 5.39 ± 1.1) and showed correlation with PT and factor V in the optimal group (p<0.05). Multivariate analysis pointed steatosis as an independent risk factor to histopathological injury (p<0.05). CONCLUSION: There was a significant GSH depletion and GSSG formation after cold storage and reperfusion due to a similar oxidative stress in optimal and suboptimal grafts, but these levels were not related to graft viability.

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Main Authors: Grezzana Filho,Tomaz de Jesus Maria, Corso,Carlos Otávio, Zanotelli,Maria Lúcia, Marroni,Cláudio Augusto, Brandão,Ajácio Bandeira Mello, Schlindwein,Eduardo, Leipnitz,Ian, Meine,Mário Henrique Mattos, Fleck Jr.,Alfeu, Hoppen,Ricardo, Kiss,Guillermo, Cantisani,Guido Pio Cracco
Format: Digital revista
Language:English
Published: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia 2006
Online Access:http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0102-86502006000400007
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spelling oai:scielo:S0102-865020060004000072006-09-20Liver glutathione depletion after preservation and reperfusion in human liver transplantationGrezzana Filho,Tomaz de Jesus MariaCorso,Carlos OtávioZanotelli,Maria LúciaMarroni,Cláudio AugustoBrandão,Ajácio Bandeira MelloSchlindwein,EduardoLeipnitz,IanMeine,Mário Henrique MattosFleck Jr.,AlfeuHoppen,RicardoKiss,GuillermoCantisani,Guido Pio Cracco Liver Transplantation Oxidative Stress Glutathione PURPOSE: The oxidative stress is an important mechanism responsible for dysfunction after orthotopic liver transplantation (OLT). Glutathione (GSH) low levels after cold storage render the grafts vulnerable to reperfusion injury. Aim of this study was to evaluate GSH and oxidized glutathione (GSSG) liver concentrations, the hepatocellular injury and function in optimal and suboptimal grafts after human OLT. METHODS: Liver biopsies were taken in 33 patients before the implant and two hours after reperfusion, allowing determination of GSH, GSSG and oxidative stress ratio (GSH/GSSG). Serum transaminases, prothrombin activity (PT) and factor V were measured to evaluate injury and function respectively. Histopathological injury was analyzed by an index of five parameters. RESULTS: There was a decrease in GSH (p<0.01) after reperfusion (0.323 ± 0.062 ìmol/g to 0.095 ± 0.01 ìmol/g and 0.371 ± 0.052 ìmol/g to 0.183 ± 0.046 ìmol/g) in suboptimal and optimal groups, respectively. An increase of GSSG (p<0.05) occurred after reperfusion (0.172 ± 0.038 ìmol/g to 0.278 ± 0.077 ìmol/g and 0.229 ± 0.048 ìmol/g to 0.356 ± 0.105 ìmol/g) in suboptimal and optimal groups, respectively. A decrease (p<0.01) occurred in the GSH/GSSG ratio after reperfusion (2.23 ± 0.31 to 0.482 ± 0.042 and 2.47 ± 0.32 to 0.593 ± 0.068) in suboptimal and optimal groups, respectively. Histopathological injury scores were higher (p<0.05) in the suboptimal group than in optimal (6.46 ± 0.4 vs. 5.39 ± 1.1) and showed correlation with PT and factor V in the optimal group (p<0.05). Multivariate analysis pointed steatosis as an independent risk factor to histopathological injury (p<0.05). CONCLUSION: There was a significant GSH depletion and GSSG formation after cold storage and reperfusion due to a similar oxidative stress in optimal and suboptimal grafts, but these levels were not related to graft viability.info:eu-repo/semantics/openAccessSociedade Brasileira para o Desenvolvimento da Pesquisa em CirurgiaActa Cirúrgica Brasileira v.21 n.4 20062006-08-01info:eu-repo/semantics/articletext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0102-86502006000400007en10.1590/S0102-86502006000400007
institution SCIELO
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country Brasil
countrycode BR
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access En linea
databasecode rev-scielo-br
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region America del Sur
libraryname SciELO
language English
format Digital
author Grezzana Filho,Tomaz de Jesus Maria
Corso,Carlos Otávio
Zanotelli,Maria Lúcia
Marroni,Cláudio Augusto
Brandão,Ajácio Bandeira Mello
Schlindwein,Eduardo
Leipnitz,Ian
Meine,Mário Henrique Mattos
Fleck Jr.,Alfeu
Hoppen,Ricardo
Kiss,Guillermo
Cantisani,Guido Pio Cracco
spellingShingle Grezzana Filho,Tomaz de Jesus Maria
Corso,Carlos Otávio
Zanotelli,Maria Lúcia
Marroni,Cláudio Augusto
Brandão,Ajácio Bandeira Mello
Schlindwein,Eduardo
Leipnitz,Ian
Meine,Mário Henrique Mattos
Fleck Jr.,Alfeu
Hoppen,Ricardo
Kiss,Guillermo
Cantisani,Guido Pio Cracco
Liver glutathione depletion after preservation and reperfusion in human liver transplantation
author_facet Grezzana Filho,Tomaz de Jesus Maria
Corso,Carlos Otávio
Zanotelli,Maria Lúcia
Marroni,Cláudio Augusto
Brandão,Ajácio Bandeira Mello
Schlindwein,Eduardo
Leipnitz,Ian
Meine,Mário Henrique Mattos
Fleck Jr.,Alfeu
Hoppen,Ricardo
Kiss,Guillermo
Cantisani,Guido Pio Cracco
author_sort Grezzana Filho,Tomaz de Jesus Maria
title Liver glutathione depletion after preservation and reperfusion in human liver transplantation
title_short Liver glutathione depletion after preservation and reperfusion in human liver transplantation
title_full Liver glutathione depletion after preservation and reperfusion in human liver transplantation
title_fullStr Liver glutathione depletion after preservation and reperfusion in human liver transplantation
title_full_unstemmed Liver glutathione depletion after preservation and reperfusion in human liver transplantation
title_sort liver glutathione depletion after preservation and reperfusion in human liver transplantation
description PURPOSE: The oxidative stress is an important mechanism responsible for dysfunction after orthotopic liver transplantation (OLT). Glutathione (GSH) low levels after cold storage render the grafts vulnerable to reperfusion injury. Aim of this study was to evaluate GSH and oxidized glutathione (GSSG) liver concentrations, the hepatocellular injury and function in optimal and suboptimal grafts after human OLT. METHODS: Liver biopsies were taken in 33 patients before the implant and two hours after reperfusion, allowing determination of GSH, GSSG and oxidative stress ratio (GSH/GSSG). Serum transaminases, prothrombin activity (PT) and factor V were measured to evaluate injury and function respectively. Histopathological injury was analyzed by an index of five parameters. RESULTS: There was a decrease in GSH (p<0.01) after reperfusion (0.323 ± 0.062 ìmol/g to 0.095 ± 0.01 ìmol/g and 0.371 ± 0.052 ìmol/g to 0.183 ± 0.046 ìmol/g) in suboptimal and optimal groups, respectively. An increase of GSSG (p<0.05) occurred after reperfusion (0.172 ± 0.038 ìmol/g to 0.278 ± 0.077 ìmol/g and 0.229 ± 0.048 ìmol/g to 0.356 ± 0.105 ìmol/g) in suboptimal and optimal groups, respectively. A decrease (p<0.01) occurred in the GSH/GSSG ratio after reperfusion (2.23 ± 0.31 to 0.482 ± 0.042 and 2.47 ± 0.32 to 0.593 ± 0.068) in suboptimal and optimal groups, respectively. Histopathological injury scores were higher (p<0.05) in the suboptimal group than in optimal (6.46 ± 0.4 vs. 5.39 ± 1.1) and showed correlation with PT and factor V in the optimal group (p<0.05). Multivariate analysis pointed steatosis as an independent risk factor to histopathological injury (p<0.05). CONCLUSION: There was a significant GSH depletion and GSSG formation after cold storage and reperfusion due to a similar oxidative stress in optimal and suboptimal grafts, but these levels were not related to graft viability.
publisher Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia
publishDate 2006
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0102-86502006000400007
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