Garlic extract prevents CCl4-induced liver fibrosis in rats: The role of tissue transglutaminase

Giuseppe D'Argenio*, Daniela Caterina Amoruso, Giovanna Mazzone, Paola Vitaglione, Antonietta Romano, Maria Teresa Ribecco, Maria Rosaria D'Armiento, Ernesto Mezza, Filomena Morisco, Vincenzo Fogliano, Nicola Caporaso

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

26 Citations (Scopus)

Abstract

Background and aim: Tissue transglutaminase contributes to liver damage in the development of hepatic fibrosis. In a model of neurodegeneration, the therapeutic benefit of cystamine has been partly attributed to its inhibition of transglutaminase activity. Garlic extract contains many compounds structurally related to cystamine. We investigated the anti-fibrotic effect of garlic extract and cystamine as specific tissue transglutaminase inhibitors. Methods: Rat liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride (CCl4) for 7 weeks. Cystamine or garlic extract was administrated by daily intraperitoneal injection, starting from the day after the first administration of CCl4. Hepatic function, histology, tissue transglutaminase immunostaining and image analysis to quantify Red Sirius stained collagen deposition were examined. Reverse transcription-polymerase chain reaction to detect alpha-SMA, IL-1β and tissue transglutaminase expression and Western blot for tissue transglutaminase protein amount were performed. Transglutaminase activity was assayed on liver homogenates by a radio-enzymatic method. Results: Transglutaminase activity was increased in CCl4 group and reduced by cystamine and garlic extract (p<0.05). Treatment with cystamine and garlic extract reduced the liver fibrosis and collagen deposition, particularly in the garlic extract group (p<0.01). Moreover, the liver damage improved and serum alanine aminotransferase was decreased (p<0.05). Tissue transglutaminase immunolocalised with collagen fibres and is mainly found in the ECM of damaged liver. Alpha-SMA, IL-1β, tissue transglutaminase mRNA and tissue transglutaminase protein were down-regulated in the cystamine and garlic extract groups compared to controls. Conclusion: These findings concurrently suggest that transglutaminase may play a pivotal role in the pathogenesis of liver fibrosis and may identify garlic cystamine-like molecules as a potential therapeutic strategy in the treatment of liver injury.

Original languageEnglish
Pages (from-to)571-577
Number of pages7
JournalDigestive and Liver Disease
Volume42
Issue number8
DOIs
Publication statusPublished - 1 Aug 2010
Externally publishedYes

Keywords

  • Cystamine
  • Garlic extract
  • Liver fibrosis
  • Tissue transglutaminase

Fingerprint Dive into the research topics of 'Garlic extract prevents CCl4-induced liver fibrosis in rats: The role of tissue transglutaminase'. Together they form a unique fingerprint.

Cite this