Mitochondrial protection by low doses of insulin-like growth factor- I in experimental cirrhosis.
World J Gastroenterol
; 14(17): 2731-9, 2008 May 07.
Article
em En
| MEDLINE
| ID: mdl-18461658
ABSTRACT
AIM:
To characterize the mitochondrial dysfunction in experimental cirrhosis and to study whether insulin-like growth factor-I (IGF- I) therapy (4 wk) is able to induce beneficial effects on damaged mitochondria leading to cellular protection.METHODS:
Wistar rats were divided into three groups Control group, untreated cirrhotic rats and cirrhotic rats treated with IGF- I treatment (2 microg/100 g bw/d). Mitochondrial function was analyzed by flow cytometry in isolated hepatic mitochondria, caspase 3 activation was assessed by Western blot and apoptosis by TUNEL in the three experimental groups.RESULTS:
Untreated cirrhotic rats showed a mitochondrial dysfunction characterized by a significant reduction of mitochondrial membrane potential (in status 4 and 3); an increase of intramitochondrial reactive oxigen species (ROS) generation and a significant reduction of ATPase activity. IGF- I therapy normalized mitochondrial function by increasing the membrane potential and ATPase activity and reducing the intramitochondrial free radical production. Activity of the electron transport complexes I and III was increased in both cirrhotic groups. In addition, untreated cirrhotic rats showed an increase of caspase 3 activation and apoptosis. IGF- I therapy reduced the expression of the active peptide of caspase 3 and resulted in reduced apoptosis.CONCLUSION:
These results show that IGF- I exerts a mitochondrial protection in experimental cirrhosis leading to reduced apoptosis and increased ATP production.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Insulin-Like I
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Mitocôndrias Hepáticas
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Cirrose Hepática Experimental
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
World J Gastroenterol
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Espanha