Protein glutathionylation increases in the liver of patients with non-alcoholic fatty liver disease

Fiorella Piemonte, Stefania Petrini, Laura Maria Gaeta, Giulia Tozzi, Enrico Bertini, Rita Devito, Renata Boldrini, Matilde Marcellini, Enzo Ciacco, Valerio Nobili

Research output: Contribution to journalArticlepeer-review


Background and Aim: Oxidative stress is an important pathophysiological mechanism in non-alcoholic steatohepatitis, where hepatocyte apoptosis is significantly increased correlating with disease severity. Protein glutathionylation occurs as a response to oxidative stress, where an increased concentration of oxidized glutathione modifies post-translational proteins by thiol disulfide exchange. In this study, we analyzed the protein glutathionylation in non-alcoholic fatty liver disease (NAFLD) and evaluated a potential association between glutathionylation, fibrosis, and vitamin E treatment. Methods: Protein glutathionylation was studied in the livers of 36 children (mean age 12.5 years, range 4-16 years) subdivided into three groups according to their NAFLD activity score (NAS) by Western blot analysis and immunohistochemistry, using a specific monoclonal antibody. In addition, we identified the hepatocyte ultrastructures involved in glutathionylation by immunogold electron microscopy. Results: Our findings showed that protein glutathionylation increases in the livers of patients with NAFLD and it is correlated with steatohepatitis and liver fibrosis. Its increase appears mainly in nuclei and cytosol of hepatocytes, and it is reversed by antioxidant therapy with reduced fibrosis. Conclusion: Protein glutathionylation significantly increases in livers with NAFLD, strongly suggesting that oxidative injury plays a crucial role in this disease. Furthermore, the marked increase of protein glutathionylation, in correlation with collagen VI immunoreactivity, suggests a link between the redox status of hepatic protein thiols and fibrosis.

Original languageEnglish
JournalJournal of Gastroenterology and Hepatology
Issue number8 PART2
Publication statusPublished - 2008


  • Glutathione
  • Glutathionylated proteins
  • Non-alcoholic fatty liver disease
  • Non-alcoholic steatohepatitis
  • Oxidative stress

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology


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