title: Advanced glycation end products augment experimental hepatic fibrosis.
abstract: OBJECTIVE
  Advanced glycation end products (AGEs) 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 AGEs can exacerbate chronic liver injury and contribute to hepatic fibrosis.
  
  
  METHODS
  We initially studied the effects of chronic hepatic exposure to high levels of AGEs 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, AGEs increased hepatic oxidative stress and receptor for advanced glycation end products gene expression.
  
  
  CONCLUSIONS
  These findings suggest that AGEs may contribute to the pathogenesis of chronic liver injury and fibrosis.
authors.affiliation: Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia. michelle.clonan@austin.org.au
authors.forename: Michelle
authors.initials: M
authors.lastname: Goodwin
authors.forename: Chandana
authors.initials: C
authors.lastname: Herath
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Jia
authors.forename: Chris
authors.initials: C
authors.lastname: Leung
authors.forename: Melinda T
authors.initials: MT
authors.lastname: Coughlan
authors.forename: Josephine
authors.initials: J
authors.lastname: Forbes
authors.forename: Peter
authors.initials: P
authors.lastname: Angus
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D003135:Common Bile Duct / Q000601:surgery; D017127:Glycation End Products, Advanced / Q000008:administration & dosage / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D008026:Ligation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012709:Serum Albumin / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000199:Actins; D015415:Biomarkers; D003094:Collagen; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D012709:Serum Albumin; C498862:Acta2 protein, rat