title: Effect of selective cyclooxygenase-2 inhibitor meloxicam on liver fibrosis in rats with ligated common bile ducts.
abstract: OBJECTIVE
  Cholestasis triggers fibrogenesis in the liver. Hepatic cyclooxygenase-2 (COX-2) expression increases in various chronic liver diseases caused either by viruses or toxins. We hypothesized that selective COX-2 inhibitor meloxicam could suppress inflammation and fibrogenesis in a rat model of cholestasis induced by bile duct ligation (BDL).
  
  
  METHODS
  Forty-three Sprague-Dawley rats were assigned to one of four treatment groups (sham-operation, BDL, daily meloxicam injections following BDL, and daily meloxicam injection without BDL). Liver histopathology was analyzed with hematoxylin-eosin and Masson's trichrome staining. The expression of alpha-smooth muscle actin (alpha-SMA), transforming growth factor-beta1 (TGF-beta1), and COX-2 were measured with immunohistochemical staining. The levels of COX-2, TGF-beta1, and matrix metalloproteinase-9 (MMP-9) production were measured with the Western blot method and an enzyme immunoassay.
  
  
  RESULTS
  Meloxicam treatment attenuated the expression of alpha-SMA, TGF-beta1, and COX-2 in rats that were treated with BDL for 3 weeks. This was associated with a marked reduction in collagen accumulation and histological improvement. In addition, meloxicam treatment was found to downregulate the levels of hepatic COX-2, TGF-beta1, and MMP-9 production.
  
  
  CONCLUSIONS
  Cholestasis in BDL rats induces hepatic COX-2 expression. Selective COX-2 inhibitor meloxicam reduces BDL-induced hepatic fibrosis, and this is associated with reduced hepatic TGF-beta1 expression as well as decreased cyclooxygenase activity in the liver.
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Seong Min
authors.initials: SM
authors.lastname: Kim
authors.forename: Ki Chung
authors.initials: KC
authors.lastname: Park
authors.forename: Ho Guen
authors.initials: HG
authors.lastname: Kim
authors.forename: Seok Joo
authors.initials: SJ
authors.lastname: Han