Therapeutic effect of melatonin on cholestatic liver injury in rats with bile duct ligation.

We examined the therapeutic effect of melatonin (MT) on cholestatic liver injury in rats with bile duct ligation (BDL). Cholestatic liver injury occurred 5 days after BDL and proceeded at 13 days, judging from the levels of serum hepatobiliary injury markers. Increases in the hepatic levels of thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, and reduced glutathione (GSH) and the hepatic activity of myeloperoxidase (MPO), an index of tissue neutrophil infiltration, were observed 5 and 13 days after BDL. When MT at a dose of 10 or 100 mg/kg body weight was orally administered to rats with BDL everyday for one week, starting 6 days after BDL, a high dose of the indoleamine significantly attenuated cholestatic liver injury at 13 days after BDL. The daily administration of a high dose of MT significantly attenuated the increases in hepatic TBARS and GSH levels and MPO activity observed 13 days after BDL. These results indicate that MT administered orally at pharmacological doses exerts a therapeutic effect on cholestatic liver injury in rats with BDL possibly through its antioxidant and anti-inflammatory actions.