| Summary: | Chronic liver disease is characterized by inflammation and fibrosis. Angiogenesis which leading to new vascu-lature may have prognostic value in disease progression. This study examined the implication of 5-lipoxy-genase pathway and angiogenic factors in hepatic fi-brosis progression and whether, the inhibition of arachidonic acid cascade product (cysteinyl leukot-rienes) can represent a potential target for therapy. Cholestasis and subsequent fibrosis was induced by common bile duct ligation and resection (BDL) for 5 weeks in rats. After surgery, Cysteinyl leukotrienes antagonist (montelukast) was orally and daily administrated (10 mg/kg) for 34 days. Sham operated and drug control groups received either saline or montelukast immediately after operation. BDL significantly increased liver hydroxyproline (Hp), nuclear factor kappa B (NF-Kβ), transforming growth factor beta (TGF-β), tissue inhibitor metalloproteinase (TIMP-1), vascular endothelial growth factor (VEGF), and reduced the level of matrix metalloproteinase 9 (MMP-9). On the other hand, montelukast treatment reversed all these biochemical parameters and ameliorated histopatho-logical changes which previously induced by BDL. Findings of the present study suggest that montelukast treatment may favor collagenolytic activity through modulating hepatic expression of TGF-β, NF-κβ, and MMP-9/TIMP-1 ratio. Amelioration of necroinflam-matory liver injury and fibrogenesis may support such assumption.
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