Rating of CCl(4)-induced rat liver fibrosis by blood serum glycomics.
BACKGROUND
Non-invasive staging of human liver fibrosis is a desirable objective that remains under extensive evaluation. Animal model systems are often used for studying human liver disease and screening antifibrotic compounds. The aim of the present study was to investigate the potential use of serum N-glycan profiles to evaluate liver fibrosis in a rat model.


METHODS
Liver fibrosis and cirrhosis were induced in rats by oral administration of CCl(4). Liver injury was assessed biochemically (alanine aminotransferase [ALT] activity, aspartate aminotransferase [AST] activity and total bilirubin) and histologically. The N-glycan profile (GlycoTest) was performed using DNA sequencer-assisted-fluorophore-assisted carbohydrate electrophoresis technology. In parallel, the effect of cotreatment with antifibrotic interferon-gamma (IFN-gamma) was studied.


RESULTS
The biopsy scoring system showed that CCl(4) induced early fibrosis (F < 1-2) in rats after 3 weeks of treatment, and cirrhosis (F4) after 12 weeks. Significant increases in ALT activity, AST activity and total bilirubin levels were detected only after 12 weeks of CCl(4) treatment. GlycoTest showed three glycans were significantly altered in the CCl(4)-goup. Peak 3 started at week 6, at an early stage in fibrosis development (F < 1-2), whereas peaks 4 and 5 occurred at week 9, at which time mild liver fibrosis (F = 1-2) had developed. The changes in the CCl(4)-IFN-gamma group were intermediate between the CCl(4)- and the control groups.


CONCLUSIONS
The GlycoTest is much more sensitive than biochemical tests for evaluating liver fibrosis/cirrhosis in the rat model. The test can also be used as a non-invasive marker for screening and monitoring the antifibrotic activity of potential therapeutic compounds.
Desmyter
Liesbeth
L
Fundamental and Applied Molecular Biology, Department for Molecular Biomedical Research, Ghent University and Flanders Interuniversity Institute for Biotechnology (VIB), Ghent, Belgium.
Fan
Ye-Dong
YD
Praet
Marleen
M
Jaworski
Tomasz
T
Vervecken
Wouter
W
De Hemptinne
Bernard
B
Contreras
Roland
R
Chen
Cuiying
C
D000818:Animals; D002251:Carbon Tetrachloride / Q000008:administration & dosage; D008103:Liver Cirrhosis / Q000097:blood* / Q000139:chemically induced; D008297:Male; D011134:Polysaccharides / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar
D011134:Polysaccharides; D002251:Carbon Tetrachloride