Attenuation of warm ischemia-reperfusion injury in the liver by bucillamine through decreased neutrophil activation and Bax/Bcl-2 modulation.
J Gastroenterol Hepatol
; 25(12): 1891-9, 2010 Dec.
Article
em En
| MEDLINE
| ID: mdl-21092002
ABSTRACT
BACKGROUND AND AIM:
Liver transplantation and resection surgery involve a period of ischemia and reperfusion to the liver, which initiates an inflammatory cascade resulting in liver and remote organ injury. Bucillamine is a low molecular weight thiol antioxidant that is capable of rapidly entering cells. We hypothesized that bucillamine acts by replenishing glutathione levels, thus reducing neutrophil activation, modulating Bax/Bcl-2 expression, and subsequently, attenuating the effects of warm ischemia-reperfusion injury (IRI) in the liver.METHODS:
The effect of bucillamine was studied in a rat model of liver IRI with 45 min of partial (70%) liver ischemia and 3 h of reperfusion. Liver injury was assessed by measuring serum transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and liver histology. Oxidative stress was quantified by measuring F(2) isoprostane and glutathione levels. Leukocyte adhesion was assessed by intravital microscopy, and inflammatory cytokine response was assessed by measuring serum cytokine-induced neutrophil chemoattractant-1 (CINC-1) levels. Bax and Bcl-2 expression was measured by reverse transcription-polymerase chain reaction.RESULTS:
The model produced significant liver injury with elevated transaminases and an acute inflammatory response. Bucillamine reduced the liver injury, as indicated by reduced AST (932 ± 200.8 vs 2072.5 ± 511.79, P < 0.05). Bucillamine reduced Bax expression, serum CINC-1 levels, and neutrophil adhesion, and upregulated Bcl-2. However, bucillamine did not affect tissue glutathione levels nor the levels of oxidative stress, as measured by plasma and hepatic F(2) isoprostane levels.CONCLUSIONS:
Bucillamine reduces warm ischemia-reperfusion in the liver by inhibiting neutrophil activation and modulating Bax/Bcl-2 expression.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão
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Ativação de Neutrófilo
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Proteínas Proto-Oncogênicas c-bcl-2
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Cisteína
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Proteína X Associada a bcl-2
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Isquemia Quente
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Fígado
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Gastroenterol Hepatol
Ano de publicação:
2010
Tipo de documento:
Article