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Background/purpose: 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. [ABSTRACT FROM AUTHOR]

Purpose: Among factors promoting intestinal adaptation after bowel resection, dietary fatty acids have a special role. The purpose of the present study was to evaluate the effects of palmitic acid (PA) on early intestinal adaptation in rats with short bowel syndrome (SBS).Materials: Male Sprague-Dawley rats underwent either a bowel transection with re-anastomosis (sham rats) or 75% small bowel resection (SBS rats). Animals were randomly assigned to one of four groups: sham rats fed normal chow (sham-NC); SBS rats fed NC (SBS-NC), SBS rats fed high palmitic acid diet (SBS-HPA), and SBS rats fed low palmitic acid diet (SBS-LPA). Rats were sacrificed on day 14. Parameters of intestinal adaptation, overall bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, cell proliferation and apoptosis were determined at sacrifice. RT-PCR and Western blotting were used to determine the level of bax and bcl-2 mRNA and protein (parameters of apoptosis), and ERK protein levels (parameter of proliferation). Statistical analysis was performed using Kruskal-Wallis test followed by post hoc test for multiple comparisons with P values of less than 0.05 considered statistically significant.Results: SBS-HFD rats demonstrated higher bowel and mucosal weight, mucosal DNA and protein in ileum, while deprivation of PA (SBS-LPA) inhibited intestinal re-growth both in jejunum and ileum compared to SBS-NC rats. A significant up-regulation of ERK protein coincided with increased cell proliferation in SBS-HFD rats (vs. SBS-NC). Also, the initial decreased levels of apoptosis corresponded with the early decrease in bax and increase in bcl-2 at both mRNA and protein levels.Conclusion: Early exposure to HPA both augments and accelerates structural bowel adaptation in a rat model of SBS. Increased cell proliferation and decreased cell apoptosis may be responsible for this effect. Deprivation of PA in the diet inhibits intestinal re-growth. [ABSTRACT FROM AUTHOR]

Purpose: Elevated intra-abdominal pressure (IAP) has been shown to reduce mesenteric blood flow and cause intestinal damage. The purpose of the present study was to evaluate the effects of IAP and hyperoxia on superior mesenteric artery (SMA) blood flow, enterocyte proliferation and apoptosis in a rat model of abdominal compartment syndrome (ACS).Methods: Male rats underwent midline laparotomy. SMA was isolated and ultrasonic blood flow probes were placed on the vessel for continuous measurement of regional blood flow. Two catheters were introduced into the peritoneal cavity for inflation of air and for measurement of IAP. Rats were divided into three experimental groups: (1) Sham rats were subjected to IAP of 0 mmHg, (2) ACS-air rats were subjected to IAP of 6 mmHg for 2 h and were ventilated with air, and (3) ACS-O(2) rats were subjected to IAP of 6 mmHg and were ventilated with 100% oxygen (O(2)) during the operation and for 6 h after the operation. Intestinal structural changes, enterocyte proliferation and enterocyte apoptosis were evaluated at 24 h after operation. A paired Student's t test and the non-parametric Kruskal-Wallis ANOVA test were used as indicated. P < 0.05 was considered statistically significant.Results: IAP at 6 mmHg caused a moderate decrease in SMA blood flow. Inhalation of 100% oxygen resulted in a trend toward an increase in SMA flow when compared to air-ventilated animals. ACS rats demonstrated a significantly lower index of proliferation in jejunum and ileum as well as a significantly greater apoptotic index in jejunum compared to sham animals. Exposure to 100% oxygen resulted in a significant increase in cell proliferation in jejunum and ileum as well as in a significant decrease in cell apoptosis in jejunum compared to air-breathing animals.Conclusions: In a rat model of ACS, elevated IAP decreases SMA blood flow and inhibits enterocyte turnover. Hyperoxia results in a trend toward an increase in SMA blood flow, increases enterocyte proliferation and inhibits cell death via apoptosis. These findings may have significant implications for ventilation strategies during laparoscopy. [ABSTRACT FROM AUTHOR]