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 microg/kg/d) intraperitoneally for 2 wk [melatonin (500 microg/kg/d) (M500) group]; and BDL rats with melatonin (1000 microg/kg/d/intraperitoneally) for 2 wk [melatonin (1000 microg/kg/d) (M1000) 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), MDA 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 dose of melatonin improved spatial performance. Results of this study indicate cholestasis in the developing rats increase oxidative stress and cause spatial memory deficits, which are prevented by melatonin treatment.
Huang
Li-Tung
LT
Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Tiao
Mao-Meng
MM
Tain
You-Lin
YL
Chen
Chih-Cheng
CC
Hsieh
Chih-Sung
CS
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001651:Cholestasis, Extrahepatic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003135:Common Bile Duct / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000031:analogs & derivatives / Q000097:blood; D019803:Glutathione Disulfide / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008026:Ligation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008550:Melatonin / Q000008:administration & dosage*; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D015415:Biomarkers; D008315:Malondialdehyde; C058293:glutathione monoisopropyl ester; D005978:Glutathione; D008550:Melatonin; D019803:Glutathione Disulfide