Melatonin Ameliorates Bile Duct Ligation-Induced Systemic Oxidative Stress and Spatial Memory Deficits in Developing Rats

Bile duct ligation (BDL) induces primary biliary cirrhosis characterized by cholestasis. impaired liver function, and cognition. Young male Sprague-Dawley rats were used: rats underwent laparotomy Without BDL [sham-control (SC) group] rats had restricted diets supply [diet-control (DC) group] rats underwent BDL for 2 wk (BDL group): BDL rats with melatonin (500 mu g/kg/d) intraperitoneally for 2 wk [melatonin (500 mu g/kg/d) (M500) group]: and BDL rats with melatonin (1000 mu g/kg/d/intraperitoneally) for 2 wk [melatonin (1000 mu g/kg/d) (M 1000) group]. All the surviving rats were assessed For spatial memory and blood was tested for biochemical Study. Liver, brain cortex, and hippocampus were collected for determination of malondialdehyde (MDA) and glutathione (GSH)/oxidized glutathione (GSSG) ratios. BDL group rats had significantly higher plasma direct/total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), NIDA values and higher liver MDA values and lower GSH/GSSG ratios when compared With SC group. In addition. BDL group rats had impaired spatial performance. After melatonin treatment, cholestatic rats' plasma MDA levels. liver MDA levels. and liver GSH/GSSG ratios approached to the values of SC group. Only high close of melatonin improved spatial performance. Results of this study indicate cholestasis in the developing rats increase oxidative stress and Cause spatial memory deficits, which Lire prevented by melatonin treatment. (Pediatr Res 65: 176-180, 2009)