The interaction between high ammonia diet and bile duct ligation in developing rats: assessment by spatial memory and asymmetric dimethylarginine.
Bile duct ligation (BDL) in developing rats causes cholestasis, impaired liver function and cognition. Because both nitric oxide (NO) and ammonia are implicated in hepatic encephalopathy (HE), we hypothesized that asymmetric dimethylarginine (ADMA), an endogenous NO synthase inhibitor, and ammonia affect cognition in young rats with BDL. Four groups of young male Sprague-Dawley rats ages 17 days were used: rat underwent laparotomy (SC group), rat underwent laparotomy plus a 30% ammonium acetate diet (SC+HA group), rat underwent BDL (BDL group), rats underwent BDL plus high ammonia diet (BDL+HA group). Spatial memory was assessed by Morris water maze task. Plasma was collected for biochemical and ADMA analyses. Liver and brain cortex were collected for determination of protein arginine methyltransferase-1 (PRMT1, ADMA-synthesizing enzyme) and dimethylarginine dimethylaminohydrolase (DDAH, ADMA-metabolizing enzyme). We found BDL group had significantly higher plasma direct/total bilirubin, aspartate aminotransferase, alanine aminotransferase, ADMA, liver p22(phox), and worse spatial performance as compared with SC group. High ammonia diet increased plasma ammonia and ADMA concentration, and aggravated spatial deficit in the presence of BDL-induced cholestasis. We conclude plasma ADMA plays a role in BDL-induced spatial deficit. High ammonia aggravated the spatial deficits encountered in cholestatic young rats.
Huang
Li-Tung
LT
Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Chen
Chih-Cheng
CC
Sheen
Jiunn-Ming
JM
Chen
Yi-Ju
YJ
Hsieh
Chih-Sung
CS
Tain
You-Lin
YL
D000284:Administration, Oral; D000641:Ammonia / Q000009:adverse effects* / Q000097:blood*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D001652:Bile Ducts / Q000187:drug effects / Q000601:surgery; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002779:Cholestasis / Q000503:physiopathology*; D008026:Ligation; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
C487735:dimethylarginine; D000641:Ammonia; D001120:Arginine