Effects of silymarin and vitamins E and C on liver damage induced by prolonged biliary obstruction in the rat.

Oxidative stress, in particular lipid peroxidation, induces collagen synthesis. Thus, we administered various antioxidants to bile duct-ligated rats for 28 days and lipid peroxidation, glutathione content, fibrosis, necrosis and cholestasis were evaluated. Extrahepatic cholestasis was induced by double ligation and section of the common bile duct. The study included eight groups (n=6), four groups were bile duct-ligated and received either vitamin C (50 mg/kg/day, orally), vitamin E (400 IU/rat/day, orally), silymarin (50 mg/kg/12 hr, orally) or vehicles; four groups were sham-operated controls. Collagen content was determined by measuring hydroxyproline in liver samples; malondialdehyde was used to estimate lipid peroxidation levels; reduced and oxidized glutathione were determined fluorometrically; alanine aminotransferase and bilirubins colorimetrically. Bilirubins increased several times, alanine aminotransferase once, reduced/oxidized glutathione ratio decreased three times, lipid peroxidation and collagen increased about three-times by biliary obstruction (p<0.05). Silymarin, vitamin E or C failed to prevent these effects significantly. It is not possible to clarify the role of oxidative stress in the fibrotic process induced by chronic biliary obstruction with the present results. Therefore, it seems reasonable to propose that a wide mixture of antioxidants, administered by the parenteral route (because cholestasis decreased the absorption of lipophilic compounds), is needed to counteract the oxidant stress produced by cholestasis.