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Advanced glycation end products augment experimental hepatic fibrosis
Author(s) -
Goodwin Michelle,
Herath Chandana,
Jia Zhiyuan,
Leung Chris,
Coughlan Melinda T,
Forbes Josephine,
Angus Peter
Publication year - 2013
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12042
Subject(s) - glycation , medicine , rage (emotion) , hepatic fibrosis , fibrosis , pathogenesis , endocrinology , oxidative stress , liver injury , albumin , advanced glycation end product , chronic liver disease , receptor , biology , cirrhosis , neuroscience
Background and Aims Advanced glycation end products ( AGE s) are nonenzymatic modifications of proteins by reducing sugars. These compounds accumulate in a number of chronic disease states, contributing to tissue injury via several mechanisms, including activation of the receptor for advanced glycation end products ( RAGE ). We aimed to investigate whether AGE s can exacerbate chronic liver injury and contribute to hepatic fibrosis. Methods We initially studied the effects of chronic hepatic exposure to high levels of AGE s given intraperitoneally as AGE ‐rat serum albumin. In a separate experiment, we examined the impact of high AGE exposure in rats following bile duct ligation ( BDL ). Results In normal rats, chronic AGE ‐rat serum albumin administration induced significant increases in α‐smooth muscle actin gene and protein expression but did not induce fibrosis or biochemical evidence of liver injury. However, in BDL animals, AGE ‐bovine serum albumin administration significantly increased hepatic fibrosis as evidenced by increased collagen content and α‐smooth muscle actin expression, compared with BDL alone. Furthermore, AGE s increased hepatic oxidative stress and receptor for advanced glycation end products gene expression. Conclusions These findings suggest that AGE s may contribute to the pathogenesis of chronic liver injury and fibrosis.