الفهرس 
Introduction and Aim of the WorkOnly 14 pages are availabe for public view
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Abstract
Type IV phosphodiesterase is (PDE4s) are high-affinity enzymes found in many tissues that are specific for the hydrolysis of cyclic AMP (cAMP). Elevations of cAMP are associated with broad anti-inflammatory effects. Because inflammation precedes and promotes the progression of liver fibrosis, the use of anti-inflammatory drugs has been proposed.
Aim: The present study was undertaken to explore the therapeutic potential of administration of low dose rolipram (2mg/Kg/day, i.p.) a PDE4 inhibitor on a model of obstructive cholestasis induced by bile duct ligation as regard changes in hepatic biochemical markers and histopathological changes.
Methods: Male Wistar rats were randomly divided into 4 groups (20.rats/each group); normal control group, sham control group, bile duct ligated (BDL) group and BDL+ rolipram treated group. Half of the animals in each group were sacrificed at the end of 1st week and the rest half were sacrificed at the end of the 3rd week of the experiment. Liver function tests were performed by measuring serum; aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), bilirubin and alkaline phosphatase (ALP). Hepatic tissues were removed for measuring; hepatic hydroxyproline, hepatic vascular endothelium growth factor (VEGF) and for histopathological examination.
Results: Bile duct ligated rats exhibited a significant increase in the serum AST, ALT, GGT, bilirubin, ALP, hepatic hydroxyproline and hepatic VEGF levels compared to their corresponding sham control group. Rolipram treatment of BDL rats produced a significant decrease in serum AST, ALT, bilirubin and hepatic hydroxyproline at the end of both first and third weeks. With significant decrease of GGT, ALP and hepatic VEGF at the end of the third week only compared to BDL group. Along with improvement of hepatic histopathological changes that followed bile duct ligation in the form of restoration of normal hepatic architecture, apparent decrease in inflammatory cellular infiltration, bile duct proliferation, periportal fibrosis and statically significant decrease of hepatic percentage area of collagen fibers deposition.
Conclusion: Low dose rolipram has antifibrotic effects in a model of obstructive cholestasis induced by bile duct ligation in Wistar rats, and may represent a new therapeutic strategy for liver fibrosis that needs further clinical studies.