RGD Reference Report - The anti-inflammatory effect of celecoxib does not prevent liver fibrosis in bile duct-ligated rats. - Rat Genome Database

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The anti-inflammatory effect of celecoxib does not prevent liver fibrosis in bile duct-ligated rats.

Authors: Yu, J  Hui, AY  Chu, ES  Go, MY  Cheung, KF  Wu, CW  Chan, HL  Sung, JJ 
Citation: Yu J, etal., Liver Int. 2008 Apr 23.
RGD ID: 2300281
Pubmed: PMID:18435714   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1478-3231.2008.01760.x   (Journal Full-text)

Background/Aims: Celecoxib was used in the treatment of inflammation in patients with cirrhosis. However, data on the progression of liver fibrosis after treatment by celecoxib are not available. This study aims to elucidate the effects of celecoxib on cholestatic liver fibrosis in rats. Methods: Rats underwent bile duct ligation (BDL) for 1 or 2 weeks to induce hepatic fibrosis. Celecoxib was introduced on day 1 after operation. The effects of celecoxib were assessed by comparison of the severity of hepatic fibrosis. Results: Infiltration of inflammatory cells and proliferation of bile ducts was seen after 1 week of BDL and fibrosis was induced after 2 weeks. Reduced alanine aminotransferase (ALT) levels and blunted expression of inflammatory factors [tumour necrosis factor-alpha, interleukin (IL)-1beta and IL-6] were seen in the liver of BDL-treated rats that received celecoxib at week 1. Although celecoxib was sufficient in suppressing the cyclo-oxygenase (COX)-2 expression in the control organ (kidney), it failed to suppress the enhanced hepatic COX-2 expression. At week 2, celecoxib did not alter the ALT level, the severity of fibrosis and hepatic collagen contents. This was associated with unchanged alpha-smooth muscle actin protein expression and tissue inhibitor of metalloproteinase-2 (TIMP-2), matrix metalloproteinase (MMP)-2 and MMP-9 mRNA expressions in the liver. Celecoxib had no effect on the BDL-dependent increase in bilirubin levels at any time point. Conclusions: The present study provides morphological and molecular biological evidences for the role of celecoxib in cholestatic liver fibrosis. Celecoxib protects against hepatic inflammation in the early stage of BDL rats, but does not have an effect on liver fibrosis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Inflammation  ISOPtgs2 (Rattus norvegicus)2300281; 2300281associated with CholestasisRGD 
Inflammation  IMP 2300281associated with CholestasisRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptgs2  (prostaglandin-endoperoxide synthase 2)

Genes (Mus musculus)
Ptgs2  (prostaglandin-endoperoxide synthase 2)

Genes (Homo sapiens)
PTGS2  (prostaglandin-endoperoxide synthase 2)


Additional Information