Antifibrotic effect of AT-1 blocker and statin in rats with hepatic fibrosis

Hepatic fibrosis is an outcome of chronic liver injury. Angiotensin II (ANG II) may play a role in the pathogenesis of hepatic fibrosis. Certain drugs such as ACE inhibitors, ANG II antagonists, and even statins could interfere with the renin angiotensin system and modulate its deleterious effects. This study was carried out to investigate the possible role of losartan and atorvastatin in liver fibrosis. Liver fibrosis was induced in rats by i.p. injection of 50% CCl₄ twice per week for 8 weeks. The rats intoxicated with CCl₄ were divided into four groups: fibrosis control; losartan group; atorvastatin group; and co-treated group. A fifth group of normal healthy rats served as a control group. The results showed that losartan and atorvastatin, either alone or in combination, significantly decreased ALT, AST, hyaluronic acid and hydroxyproline levels in their groups compared to those of the fibrosis control group. A significant decrease in TGF-β was found in the losartan and co-treated groups but not in the atorvastatin group. These biochemical data were supported by liver histopathology and α-SMA. The results indicate that the combined treatment with both losartan and atorvastatin produced a greater effect than either drug alone and proved a beneficial role in inhibiting or reversing liver fibrosis.