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

被引：34

作者：

D'Argenio, Giuseppe ^{[1
]}

Amoruso, Daniela Caterina ^{[1
]}

Mazzone, Giovanna ^{[1
]}

Vitaglione, Paola ^{[2
]}

Romano, Antonietta ^{[1
]}

Ribecco, Maria Teresa ^{[1
]}

D'Armiento, Maria Rosaria ^{[3
]}

Mezza, Ernesto ^{[3
]}

Morisco, Filomena ^{[2
]}

Fogliano, Vincenzo ^{[2
]}

Caporaso, Nicola ^{[1
]}

机构：

[1] Univ Naples Federico II, Dept Clin & Expt Med, Gastroenterol Unit, Naples, Italy

[2] Univ Naples Federico II, Dept Food Sci, Naples, Italy

[3] Univ Naples Federico II, Dept Biomorphol Sci, Naples, Italy

来源：

DIGESTIVE AND LIVER DISEASE | 2010年 / 42卷 / 08期

关键词：

Cystamine; Garlic extract; Liver fibrosis; Tissue transglutaminase; NEURODEGENERATIVE DISEASES; ORGANOSULFUR COMPOUNDS; HUNTINGTONS-DISEASE; CROSS-LINKING; CYSTAMINE; RESOLUTION; MODEL;

D O I：

10.1016/j.dld.2009.11.002

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

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 beta 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 beta, 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. (C) 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

引用

页码：571 / 577

页数：7

共 31 条

[1]

Garlic shows promise for improving some cardiovascular risk factors [J].