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

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

doi:10.1016/j.dld.2009.11.002

« Previous Next »Digestive and Liver Disease
Volume 42, Issue 8 , Pages 571-577, August 2010

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

Giuseppe D’Argenio
- Gastroenterology Unit, Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy
- Corresponding author at: Dipartimento di Medicina Clinica e Sperimentale, Gastroenterologia, Facoltà di Medicina, Università Federico II, Via Pansini, 5, 80131, Napoli, Italy. Tel.: +39 081 7462706; fax: +39 081 7462739.
Daniela Caterina Amoruso
- Gastroenterology Unit, Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy
Giovanna Mazzone
- Gastroenterology Unit, Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy
Paola Vitaglione
- Department of Food Science, Federico II University, Naples, Italy
Antonietta Romano
- Gastroenterology Unit, Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy
Maria Teresa Ribecco
- Gastroenterology Unit, Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy
Maria Rosaria D’Armiento
- Department of Biomorphological Science, Federico II University, Naples, Italy
Ernesto Mezza
- Department of Biomorphological Science, Federico II University, Naples, Italy
Filomena Morisco
- Department of Food Science, Federico II University, Naples, Italy
Vincenzo Fogliano
- Department of Food Science, Federico II University, Naples, Italy
Nicola Caporaso
- Gastroenterology Unit, Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy

Received 24 July 2009; accepted 4 November 2009. published online 09 December 2009.

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.

Keywords: Cystamine, Garlic extract, Liver fibrosis, Tissue transglutaminase