Bile duct ligation in developing rats: temporal progression of liver, kidney, and brain damage.
OBJECTIVE
Cholestatic liver disease may result in progressive end-stage liver disease and other extrahepatic complications. We explored the temporal progression of bile duct ligation (BDL)-induced cholestasis in developing rats, focusing on brain cognition and liver and kidney pathology, to elucidate whether these findings were associated with asymmetric dimethylarginine and oxidative stress alterations.


METHODS
Three groups of young male Sprague-Dawley rats were studied: one group underwent laparotomy (sham), another group underwent laparotomy and BDL for 2 weeks (BDL2), and a third group underwent laparotomy and BDL for 4 weeks (BDL4).


RESULTS
The effect of BDL on liver was represented by transforming growth factor beta1 levels and histology activity index scores, which were worse in the BDL4 rats than in the BDL2 rats. BDL4 rats also exhibited more severe spatial memory deficits than BDL2 rats. In addition, renal injury was more progressive in BDL4 rats than in BDL2 rats because BDL4 rats displayed higher Cr levels, elevated tubulointerstitial injury scores, neutrophil gelatinase-associated lipocalin, and symmetric dimethylarginine levels.


CONCLUSIONS
Our findings highlight the fact that young BDL rats exhibit similar trends of progression of liver, kidney, and brain damage. Further studies are needed to better delineate the nature of progression of organ damage in young cholestatic rats.
Sheen
Jiunn-Ming
JM
Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University, College of Medicine, Kaohsiung 833, Taiwan.
Huang
Li-Tung
LT
Hsieh
Chih-Sung
CS
Chen
Chih-Cheng
CC
Wang
Jia-Yi
JY
Tain
You-Lin
YL
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D001652:Bile Ducts / Q000601:surgery*; D001921:Brain / Q000473:pathology*; D001927:Brain Diseases / Q000097:blood / Q000209:etiology / Q000473:pathology; D002779:Cholestasis / Q000097:blood / Q000150:complications* / Q000473:pathology*; D018450:Disease Progression; D058625:End Stage Liver Disease / Q000097:blood / Q000209:etiology / Q000473:pathology; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000097:blood / Q000209:etiology / Q000473:pathology; D007813:Laparotomy; D008026:Ligation; D054834:Lipocalins; D008099:Liver / Q000473:pathology*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D054834:Lipocalins; C018524:N,N-dimethylarginine; D001120:Arginine