Alterations in NADPH oxidase expression and blood-brain barrier in bile duct ligation-treated young rats: effects of melatonin.
Bile duct ligation (BDL)-treated rats exhibit cholestasis and increased systemic and brain oxidative stress. Activation of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase and disruption of the blood-brain barrier (BBB) are implicated as the pathogenetic mechanisms of brain dysfunction in BDL-treated adult rats. Young rats underwent sham ligation or BDL at day 17 for 2 or 4weeks. Treatment group rats were administered melatonin between day 17 and 45. We found a progressive increase in prefrontal cortex NADPH-dependent superoxide anion (O(2)(-)) production and increased expression of NADPH oxidase subunits in either the prefrontal cortex or the hippocampus in BDL-treated young rats. In addition, expression of intercellular adhesion molecule-1 (ICAM) and tissue plasminogen activator (t-PA) genes were increased in either the prefrontal cortex or the hippocampus. Prefrontal cortex capillary junctional complex proteins expressions including occludin, claudin-5, platelet endothelial cell adhesion molecule-1 and vascular endothelial cadherin were not altered. Melatonin lowered the prefrontal cortex NADPH-dependent O(2)(-) production and t-PA gene expression. We conclude that alterations in NADPH oxidase expression and BBB are involved in brain dysfunction in BDL-treated young rats. In addition, melatonin regulates NADPH oxidase activity and t-PA gene expression.
Department of Pediatrics, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Yu-Chieh
YC
Chen
Jiunn-Ming
JM
Sheen
You-Lin
YL
Tain
Chih-Cheng
CC
Chen
Miao-Meng
MM
Tiao
Ying-Hsien
YH
Huang
Chih-Sung
CS
Hsieh
Li-Tung
LT
Huang
D000818:Animals; D001652:Bile Ducts / Q000601:surgery*; D001812:Blood-Brain Barrier; D015153:Blotting, Western; D008550:Melatonin / Q000494:pharmacology*; D019255:NADPH Oxidases / Q000378:metabolism*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D019255:NADPH Oxidases; D008550:Melatonin