الفهرس 
Liver CirrhosisOnly 14 pages are availabe for public view
 |  | from | 276 |  |  |
| | | from | 276 | | |
Abstract
In Egypt, hepatic fibrosis and subsequently cirrhosis are believed to be a national problem. The Egyptian liver has been struggling with many causative agents leading to its damage; of which, both hepatitis C-infection and bilharzial-infection are believed to be the two most outstanding causes of liver fibrosis/cirrhosis. The liver has metabolic, excretory and synthetic functions. A fibrotic/cirrhotic liver fails to perform such important physiological functions essential for human body. Up to date, patients suffering from hepatic fibrosis/cirrhosis are treated in such a way to compensate such impaired hepatic functions; treatment of complications; without receiving actual antifibrotic agents.
Search for new, effective and safe antifibrotic agents is still in progress. The current study was carried out to evaluate the potential antifibrotic activity of five selected therapeutic agents; Sildenafil citrate (Viagra®) (10 mg/kg/rat and 14 mg/kg/ mice), Halofuginone hydrobromide (Tempostatin®) (2 mg/kg/rat and 2 μg/kg/ mice), Tranilast (Tranilast®) (300 mg/kg/rat and 400 mg/kg/ mice), Imatinib mesylate (Gleevec®) and Nilotinib hydrochloride (Tasinga®) (20 mg/kg/rat and 50 mg/kg/ mice). Hypothetically, antifibrotic therapies would target different areas in the fibrogenic cascade preventing fibrosis/cirrhosis progression.
This study was undertaken to evaluate the activities of these potential antifibrotic drugs on both the prevention and the treatment of thioacetamide-induced liver cirrhosis in rats and S.mansoni-induced liver fibrosis in mice. In the current study, the research protocol focused on evaluating the feasibility of reversibility of liver fibrosis/cirrhosis. The patterns of progressive and regressive fibrogenesis process were used to evaluate the potential antifibrotic activity of the drugs under investigation. Drugs were administrated orally to mimic clinical practice and once daily for the indicated time intervals.
The following parameters were estimated: Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), both as indicators for hepatocyte integrity, serum total and direct bilirubin and alkaline phosphatase (ALP), both as indicators for the efficacy of hepatic excretory functions, serum albumin, as an indicator for the efficacy of hepatic synthetic functions, serum γ-glutamyl transferase (γ-GT), as a marker for biliary cirrhosis, hepatic hydroxyproline and collagen content as an indicator for the extent of hepatic fibrosis/cirrhosis, serum transforming growth factorβ1 (TGFβ1) as an indicator for the expression of profibrogenic mediators, and fibrosis grade, inflammation score and histopathological changes in hematoxylin eosin and Masson’s trichrome stained specimens.