title: Effect of alpha-naphthylisothiocyanate-induced liver injury on intestinal adaptation in a rat model of short bowel syndrome.
abstract: OBJECTIVE
  Progressive hyperbilirubinemia and end-stage liver failure are among the most serious complications of short bowel syndrome (SBS), representing the principle cause of death in a majority of fatal cases. In the current study, we examined the effects of alpha-naphthylisothiocyanate (ANIT)-induced liver injury on intestinal adaptation in a rat model of SBS.
  
  
  METHODS
  Male rats were divided into four groups: Sham rats underwent bowel transection (n = 8), Sham liver-injury rats underwent bowel transection and IP injection of ANIT (100 mg/kg, n = 8), SBS rats underwent a 75% bowel resection, and SBS-ANIT rats underwent bowel resection and liver injury similar to group sham-ANIT (n = 8). Fourteen days after intervention, liver biopsies and intestinal samples were obtained and evaluated for liver damage and measures of intestinal adaptation. Real time PCR and Western blotting were used to determine the level of bax and bcl-2 mRNA and protein, and p-ERK protein levels. Statistical analysis was performed using the one-way ANOVA test, with p < 0.05 considered statistically significant.
  
  
  RESULTS
  All ANIT-treated animals exhibited histological evidence of liver damage that was associated with the expansion of atypical ductal proliferation near the periportal areas, intense neutrophil infiltration in the liver, increased mitotic activity, Kupfer cells hyperplasia and fatty liver degeneration. ANIT-induced liver damage in bowel resected animals was associated with a significant decrease in all parameters of intestinal adaptation including bowel and mucosal weight in jejunum (twofold decrease) and ileum (twofold decrease), mucosal DNA in jejunum (fourfold decrease), mucosal protein in jejunum (threefold decrease) and ileum (threefold decrease), villus height in jejunum (38%) and ileum (34%), and crypt depth in jejunum (24%) and ileum (30%) compared to SBS animals. Both Sham-ANIT and SBS-ANIT rats demonstrated decreased enterocyte proliferation rates that were accompanied by decreased p-ERK protein levels. Lower apoptotic rates in jejunum (40%) and ileum (52%) in SBS-ANIT rats (vs. SBS) coincided with decreased bax mRNA and protein levels.
  
  
  CONCLUSIONS
  In a rat model of SBS, ANIT-induced liver injury was associated with decreased enterocyte proliferation and inhibited intestinal adaptation.
authors: Laboratory of Intestinal Adaptation and Recovery, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. igor-dr@internet-zahav.net
authors: Igor
authors: I
authors: Sukhotnik
authors: Hila
authors: H
authors: Razon
authors: Yulia
authors: Y
authors: Pollak
authors: Lili
authors: L
authors: Hayari
authors: Jacob
authors: J
authors: Bejar
authors: Jorge G
authors: JG
authors: Mogilner
authors: Karl G
authors: KG
authors: Sylvester
mesh_terms: D015058:1-Naphthylisothiocyanate / Q000633:toxicity; D000222:Adaptation, Physiological / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3 / Q000096:biosynthesis / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012778:Short Bowel Syndrome / Q000150:complications / Q000235:genetics / Q000473:pathology*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: D051028:bcl-2-Associated X Protein; D015058:1-Naphthylisothiocyanate; D004247:DNA; D053148:Caspase 3