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Garlic extract prevents CCl4-induced liver fibrosis in rats: The role of tissue transglutaminase
- Source :
- Digestive and Liver Disease, 42(8), 571-577, Digestive and Liver Disease 42 (2010) 8
- Publication Year :
- 2010
-
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-1 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-1, 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.
- Subjects :
- Liver Cirrhosis
Tissue transglutaminase
medicine.medical_treatment
Interleukin-1beta
Pharmacology
chemistry.chemical_compound
Liver Function Tests
Fibrosis
Enzyme Inhibitors
Carbon Tetrachloride
Liver injury
medicine.diagnostic_test
biology
Reverse Transcriptase Polymerase Chain Reaction
Gastroenterology
food and beverages
Biochemistry
Collagen
Injections, Intraperitoneal
hepatic fibrosi
Intraperitoneal injection
Liver fibrosis
Cystamine
Down-Regulation
Injections
transglutaminase
Western blot
medicine
Animals
Intraperitoneal
Garlic
Transglutaminases
Hepatology
business.industry
Animal
Plant Extracts
Garlic extract
Actins
Disease Models, Animal
Rats
medicine.disease
chemistry
Disease Models
biology.protein
Liver function tests
Hepatic fibrosis
business
Subjects
Details
- Language :
- English
- ISSN :
- 15908658
- Database :
- OpenAIRE
- Journal :
- Digestive and Liver Disease, 42(8), 571-577, Digestive and Liver Disease 42 (2010) 8
- Accession number :
- edsair.doi.dedup.....8f55bddef193d2c253f0846107c38580