Small Bowel Resection In Rat Research Articles

Regulation of glutathione redox status in adapting ileal mucosa after massive small bowel resection in rats

Regulation of glutathione redox status in adapting ileal mucosa after massive small bowel resection in rats

Regulation of glutathione redox status in adapting ileal mucosa after massive small bowel resection in rats

Regulation of glutathione redox status in adapting ileal mucosa after massive small bowel resection in rats

Zinc, Copper, and Metallothionein Metabolism after Jejunoileal Bypass Surgery or Small Bowel Resection in Rats

Liver dysfunction is a frequent complication of jejunoileal bypass (JIB) surgery, a procedure commonly used until recently to treat morbid obesity. It has been suggested that liver failure in JIB patients is due to bacterial overgrowth and translocation from the bypassed intestine. Because invading microorganisms cause hepatic inflammation these experiments evaluated zinc, copper, and metallothionein (MT) in two experimental rat models of intestinal surgery to determine whether their distribution in plasma and tissues was similar to the highly characteristic pattern observed during an inflammatory response. In the JIB rat model 90 per cent of the small intestine was isolated from the flow of digesta but remained viable in the abdominal cavity. In the small bowel resection (SBR) model 90 per cent of the small intestine was removed and the remaining intestine was resected. Data collected 21 days after surgery showed decreased growth rate and plasma zinc in the SBR and JIB rats that was significantly improved by supplemental zinc. All other measures of zinc, copper, and MT metabolism in the SBR rats were similar to those of controls. In JIB rats, however, liver copper, MT protein, and MT mRNA were significantly elevated, and a high proportion of the intracellular zinc and copper was associated with MT. The pattern of zinc, copper, and MT distribution in systemic circulation and liver of JIB rats suggests hepatic inflammation superimposed on low zinc and copper status. Lack of a similar response in the SBR rats confirms the involvement of the bypassed intestinal segment and supports the hypothesis that bacterial overgrowth and translocation are responsible for liver inflammation and dysfunction in JIB patients.

GH decreases hepatic amino acid degradation after small bowel resection in rats without enhancing bowel adaptation.

Growth hormone (GH) treatment in short bowel syndrome is controversial, and the mechanisms of a possible positive effect remain to be elucidated. Rats were randomly subjected to either an 80% jejunoileal resection or sham operation and were given either placebo (NaCl) or biosynthetic rat GH (brGH). The in vivo capacity of urea nitrogen synthesis (CUNS) and the expression of urea cycle enzymes were measured and related to changes in body weight and adaptive growth in ileal segments on days 7 and 14. Ileal segments were examined by unbiased stereological techniques. brGH treatment decreased CUNS among the resected rats by 19% (P<0.05) and 36% (P<0.05) on days 7 and 14, respectively. The mRNA levels of urea cycle enzyme genes were not influenced by brGH treatment. brGH treatment did not increase the adaptive growth in the ileal segments. In conclusion, we found that GH treatment decreased the accelerated postoperative hepatic amino acid degradation in experimental short bowel syndrome without enhancing the morphological intestinal adaptation.

Non-effect of hexamethonium, a ganglionic blocker, on the response of ileal apolipoprotein A-IV mRNA following a massive small bowel resection in rats.

An intravenous infusion of hexamethonium, a ganglionic blocker, did not affect the increase in the apolipoprotein A-IV mRNA level in the residual ileum following a massive small bowel resection in unrestrained conscious rats. The result suggests that upregulation of the apolipoprotein A-IV gene in the residual ileum is not mediated by a neural pathway, including the nicotinic synapse route.

Effects of Oral Saccharomyces boulardii on Bacterial Overgrowth, Translocation, and Intestinal Adaptation after Small-Bowel Resection in Rats

Small-bowel resection in animals results in alterations of the morphology and functional adaptation in the remaining intestine. The aim of our study was to study the effect of Saccharomyces boulardii versus placebo in rats after 50% small-bowel resection. Sixty-three rats were assigned to one of three groups: small-bowel resection (n = 31), transected surgery controls (n = 16), or non-surgical controls (n = 16). Of the 31 rats with small-bowel resection, 15 were given S. boulardii (140 mg/dl), and 16 were given placebo. Intestinal markers measured included bacterial overgrowth (BO) on days 4 and 8 and translocation into mesenteric lymph nodes, liver, and spleen. Markers of small-bowel adaptation included histomorphology of the mucosa, protein content, and various brush-border enzymes (sucrase, glucoamylase, n-aminopeptidase). In the jejunal mucosal samples on day 8, S. boulardii-treated rats showed a significant increase in protein content (58.3 +/- 12 mg/10 cm) compared with placebo-treated rats (29.2 +/- 1.8) or non-surgery controls (18.3 +/- 1.2; P < 0.001). S. boulardii-treated rats also had significantly higher levels of all three brush-border enzymes. A significant increase of enzyme-specific activities was observed in the ileum of S. boulardii resected rats compared with the placebo resected group on day 4, and no significant differences were seen in the remnant ileum except an increase in protein content in S. boulardii-treated rats on day 8. Histomorphometric studies showed no differences in ileal villus height or translocation frequencies by day 8 in S. boulardii or placebo resected rats. These data indicate that, after resection, S. boulardii does not modify bacterial overgrowth or translocation frequency but does significantly enhance the functional adaptation of the remaining intestinal segments.

Renal arginine metabolism in fasted rats with subacute short bowel syndrome

1. Arginine can be produced in the kidney from citrulline. An important source of circulating citrulline is the intestinal breakdown of glutamine. Consequently, partial enterectomy leads to decreased plasma citrulline levels. The aim of the present study was to investigate the effect of diminished arterial citrulline levels on renal arginine production and total-body free arginine pools.2. Renal amino acid metabolism was studied 24 h after 75% small bowel resection in rats fasted overnight (16 h) (n=12; total fast 40 h). Sham-operated (n=9) and non-operated 16-h and 40-h fasted controls were studied in parallel (n=8/n=7). During anaesthesia, L-(2, 3-3H)-arginine and para-aminohippuric acid were infused until steady state. Subsequently, arterial and renal venous blood samples were taken. Concentrations of para-aminohippurate and amino acids and specific activity of arginine and citrulline were measured to calculate renal plasma flow, net renal uptake or release, and unidirectional influx or efflux of arginine and citrulline, as well as whole-body arginine turnover.3. Arterial citrulline was decreased in enterectomized rats compared with sham-operated rats (23+/-3 versus 44+/-6 microM). Net renal citrulline uptake and arginine release were almost stoichiometric (-36+/-7 and 38+/-6 nmol.min-1. 100 g-1 body weight respectively in sham-operated rats) and were both diminished by 50% in enterectomized versus sham-operated rats. In all groups, net renal arginine production accounted for less than 10% of whole-body rate of arginine appearance (488 nmol.min-1.100 g-1 body weight in the sham group). Despite decreased net renal citrulline consumption and renal arginine production in enterectomized rats, whole-body rate of arginine appearance and arterial arginine did not change significantly.4. In conclusion, net renal arginine production is reduced 24 h after 75% enterectomy in fasted rats. However, this does not have important effects on whole-body arginine production.

Renal arginine metabolism in fasted rats with subacute short bowel syndrome

1.Arginine can be produced in the kidney from citrulline. An important source of circulating citrulline is the intestinal breakdown of glutamine. Consequently, partial enterectomy leads to decreased plasma citrulline levels. The aim of the present study was to investigate the effect of diminished arterial citrulline levels on renal arginine production and total-body free arginine pools. 2.Renal amino acid metabolism was studied 24 ;h after 75% small bowel resection in rats fasted overnight (16 ;h) (n = 12; total fast 40 ;h). Sham-operated (n = 9) and non-operated 16-h and 40-h fasted controls were studied in parallel (n = 8/n = 7). During anaesthesia, l-(2,3-3H)-arginine and para-aminohippuric acid were infused until steady state. Subsequently, arterial and renal venous blood samples were taken. Concentrations of para-aminohippurate and amino acids and specific activity of arginine and citrulline were measured to calculate renal plasma flow, net renal uptake or release, and unidirectional influx or efflux of arginine and citrulline, as well as whole-body arginine turnover. 3.Arterial citrulline was decreased in enterectomized rats compared with sham-operated rats (23±3 versus 44±6 ;μM). Net renal citrulline uptake and arginine release were almost stoichiometric (-36±7 and 38±6 ;nmol·min-1·100 ;g-1 body weight respectively in sham-operated rats) and were both diminished by 50% in enterectomized versus sham-operated rats. In all groups, net renal arginine production accounted for less than 10% of whole-body rate of arginine appearance (488 ;nmol·min-1·100 ;g-1 body weight in the sham group). Despite decreased net renal citrulline consumption and renal arginine production in enterectomized rats, whole-body rate of arginine appearance and arterial arginine did not change significantly. 4.In conclusion, net renal arginine production is reduced 24 ;h after 75% enterectomy in fasted rats. However, this does not have important effects on whole-body arginine production.

R19 Effect of oral glutamine supplementation ongrowth, nitrogen balance and hepatic steatosis after 60% small bowel resection in rats

R19 Effect of oral glutamine supplementation ongrowth, nitrogen balance and hepatic steatosis after 60% small bowel resection in rats

Effect of 50% Small Bowel Resection on Gastric Prostaglandin E 2 Levels in Rats

The mechanism for the production of increased gastric secretion following massive intestinal resection is not clearly defined. The loss of an intestinal inhibitor has been most frequently suggested to explain this hypersecretion. The role of endogenous prostaglandins which can inhibit gastric secretion is not established. The present study was undertaken to determine the effect of 50% proximal small bowel resection on Prostaglandin E 2 (PGE 2) levels in rat gastric mucosa. This study was performed in 30 rats divided into three groups. The first group of rats served as unoperated controls, the second group was sham operated and the third group underwent 50% resection of proximal small intestine. The PGE 2 levels in rat gastric mucosa was decreased significantly (p < 0.001) in the resection group (422.85 ± 7.66 pg/gm) as compared with the sham group (478.77 ± 7.25 pg/gm) and the control group (493.38 ± 4.61 pg/gm). Total gastric acidity was increased significantly (p llt 0.001) in the resection group (63.05 ± 2.64 mEq/L) as compared with the sham group (15.21 ± 0.99 mEq/L) and the control group (17.19 ± 0.80 mEq/L). The PGE 2 levels and total gastric acidity were not significantly changed in either the control or sham operation groups (p > 0.05). The results suggest that endogenous prostaglandin synthesis has a regulatory role in gastric hyperacidity after 50% proximal small bowel resection in rats.

Fecal polyamine concentration in children with and without nutrient malabsorption.

Fermentation products of malabsorbed nutrients are thought to be responsible for intestinal adaptation following small bowel resection in rats. It has been suggested that either short-chain fatty acids or polyamines (mainly putrescine and cadaverine) could be the fermentation products involved. There are no data available on fecal polyamine content in humans. The present study compared the fecal polyamine concentrations in children with and without malabsorption. Sixteen (8 girls, 8 boys) malabsorption patients (cystic fibrosis: 13, short bowel syndrome: 2, biliary atresia: 1) with a mean age of 8 years were compared to 17 (9 girls, 8 boys) sick children without malabsorption (mean age 5.7 years). Three-day fecal collections were performed and analyzed for fat and polyamine concentrations. High-performance liquid chromatography (HPLC) was used for the measurement of polyamine concentrations. Mean and SEM for fecal fat excretion was 13.4 +/- 2.5 g/day and 1.5 +/- 0.3 g/day in the malabsorption and control group respectively. Median fecal cadaverine and putrescine concentrations were 3723 mumol.kg-1 feces and 4737 mumol.kg-1 feces for the malabsorption group and 114 mumol.kg-1 feces and 306 mumol.kg-1 feces for the control group (p < 0.007 and < 0.00001 respectively). No significant differences were found for fecal spermine and spermidine concentrations between the two groups. Children with malabsorption show very high fecal putrescine and cadaverine concentrations. Our results support the hypothesis that fecal polyamines could be important.

Different Responses of Apolipoprotein A-I, A-IV, and B Gene Expression during Intestinal Adaptation to a Massive Small Bowel Resection in Rats

Gene expression of apolipoproteins (apo) A-I, A-IV, and B, the predominant protein components of chylomicrons, was investigated in the residual ileum after a massive small bowel resection in rats. A Northern blot analysis showed that the apo A-IV mRNA level, but not the apo A-I and B mRNA levels, in the ileum was significantly higher in the resected rats than in the sham-operated rats 24 h and 2 wk post-surgery. RT-PCR coupled with a primer extension assay revealed that the apo B-48 mRNA/apo B-100 mRNA ratio, i.e., apo B mRNA editing, in the ileum was unchanged by the resection. It is thus concluded that, among the major intestinal apolipoproteins, apo A-IV is the only one whose gene expression is influenced by loss of the proximal intestine.

Gut adaptation and the insulin-like growth factor system: regulation by glutamine and IGF-I administration.

Intestinal adaptation after extensive small bowel resection in rats is augmented by the provision of diets supplemented with the amino acid glutamine (Gln) or by administration of insulin-like growth factor-I (IGF-I). The goal of this study was to investigate potential synergistic effects of Gln and IGF-I on postresection ileal hyperplasia. Rats underwent 80% small bowel resection (SBR) and then were fed low-Gln or L-Gln-enriched diets and subcutaneously given recombinant human IGF-I or vehicle for 7 days. Gln and IGF-I each significantly enhanced adaptive ileal hyperplasia (DNA content) compared with rats receiving vehicle and low-Gln diet. Ileal DNA content was highest when IGF-I was administered together with Gln supplementation. Combined IGF-I plus Gln synergistically increased ileal weight and protein content. This was associated with higher plasma concentrations of IGF-I and Gln than observed when IGF-I or Gln was given individually. Ileal IGF-I mRNA expression rose nearly twofold during gut adaptation after SBR; this response was augmented with IGF-I administration but was unaltered by Gln feeding. In contrast, dietary Gln, but not IGF-I therapy, prevented a decrease in hepatic IGF-I mRNA induced by SBR. We conclude that parenteral IGF-I and enteral Gln have both individual and synergistic effects on ileal adaptation after massive small intestinal resection. These findings support the concept that specific gut-trophic nutrients and growth factors may be combined to enhance intestinal adaptation and possibly reduce the severity of short bowel syndrome after intestinal resection.

P.17 Enteral administration of ornithine α-ketoglutarate after small bowel resection in rats: changes in intestinal mucosa

P.17 Enteral administration of ornithine α-ketoglutarate after small bowel resection in rats: changes in intestinal mucosa

Altered polyamine biosynthesis with aging after massive proximal small bowel resection in rat.

We examined the effect of aging on polyamine biosynthesis in the small intestine. Two groups of male Wistar rats (young; 10-week-old, n = 40; old; 24-month-old, n = 40) underwent either a jejunal transection and reanastomosis or 90% proximal small bowel resection. The rats were sacrificed on the 1st, 2nd, 4th, and 7th postoperative day (POD). The mucosa was submitted for histological examination, weighed, and assayed for protein, DNA, RNA, and polyamine content. Ornithine decarboxylase (ODC) activity was measured and ODC mRNA in the mucosa was determined by Northern blot analysis. Compared with the values for wet weight and protein content in old rats, young rats showed significantly higher values for wet weight on the 1st and 2nd POD, and for protein content on the 1st POD, but there were no differences between young and old rats after the 4th POD. The values for ODC activity and ODC mRNA were significantly lower in old rats than in young rats on the 1st POD, but there were no differences between young and old rats after the 2nd POD. The value for putrescine in old rats was significantly lower on the 2nd POD, but was significantly higher on the 4th POD than that in young rats. The present study showed that, in old rats, the residual intestine after small bowel resection preserved sufficient adaptive capacity, but that the adaptive response was decreased. The findings in this study also suggest that a decrease in ODC mRNA expression is involved in the decreased adaptive response that occurs with aging.

Effects of dietary menhaden oil on mucosal adaptation after small bowel resection in rats

Adaptive hyperplasia of the small intestine is important in the outcome of short bowel syndrome. Previous studies have shown that long-chain fats stimulate this process. In the present study, the trophic effects of dietary menhaden oil, a highly unsaturated fat source, on mucosal adaptation following small bowel resection in rats was evaluated. Thirty weanling Sprague-Dawley rats and their controls were fed diets containing fats provided primarily as menhaden oil, safflower oil, or beef tallow. After 4 weeks, animals underwent a 70% jejunoileal resection. Mucosal mass, DNA, protein, and sucrase levels were assessed 14 days after a 70% jejunoileal resection or control feeding. Serum fatty acid composition and several gastrointestinal hormone levels were measured. Resected animals fed menhaden oil showed a marked increase in mucosal weight, DNA, and protein levels compared with rats fed the other fat sources. Enteroglucagon level was increased in all resected groups, but least increased in the menhaden-fed animals. In contrast, peptide YY concentrations were most increased in animals fed menhaden oil. Menhaden oil appears more effective in inducing intestinal adaptation than less highly unsaturated fats. Analysis of gastrointestinal hormones revealed no clear-cut explanation for this finding, other than a modest but associated increase in peptide YY levels.

Treatment with IGF-I peptides improves function of the remnant gut following small bowel resection in rats.

The effects of 7 days' s.c. infusion of 111-700 micrograms/day IGF-I on gut growth and absorptive function were examined in growing rats following removal of 70 or 80% of the jejuno-ileum, and compared with the responses to the analogues, LR3IGF-I and des(1-3)IGF-I, which bind poorly to IGF binding proteins. Administration of 278 micrograms/day IGF-I, LR3IGF-I or des(1-3)IGF-I following 70% jejuno-ileal resection significantly attenuated malabsorption of fat and nitrogen. Responses in rats with 80% resection were less substantial, but a dose-responsive reduction in malabsorption was apparent with LR3IGF-I. Both IGF-I and LR3IGF-I were shown to increase body weight gain and food conversion efficiency in a dose-dependent manner following 80% jejuno-ileal resection. Total gut weight was increased by up to 21%, due predominantly to increased weight of the stomach and proximal small bowel, with the latter effect attributable at least in part to an increased bowel length. LR3IGF-I was more potent than IGF-I at stimulating body weight gain and food conversion efficiency, but its potency advantage on gut absorptive function and small intestinal re-growth was less marked. We conclude that administration of IGF-I peptides improves gastro-intestinal absorptive function following partial gut resection, most likely reflecting, at least in part, an increase in gut absorptive surface area.

Age-related changes in duodenal adaptation after distal small bowel resection in rat.

Two groups of male Fisher 344 rats (young: 4 months old; aged: 25 months old) underwent either 70% distal small bowel resection or sham operation (small bowel transection). Rats from each treatment group of each age were sacrificed on the 10th (N = 15: young rats; N = 13: aged rats) or 20th (N = 15: young; N = 13: aged) postoperative day (POD), and the duodenal mucosa was weighed and assayed for DNA, RNA, and protein contents, as well as for specific activities of the disaccharidase, sucrase, maltase, and lactase. Compared to the sham operation, distal small bowel resection significantly increased DNA by 48%, RNA by 122%, and protein by 75% in young rats and DNA by 40%, RNA by 92%, and protein by 71% in aged rats on the 20th POD. Both young and aged rats showed similar adaptive hyperplasia on the 10th POD. On the 20th POD after distal small bowel resection, specific activities of all tested enzymes were significantly increased in young rats (sucrase +86%, maltase +110% and lactase +64%), but showed no significant changes in aged rats. These findings suggest that the duodenum of aged rats may have sufficient proliferative potential to respond to distal small bowel resection, but that the mechanisms governing return of function in response to distal small bowel resection are inhibited in aged rats, compared to those mechanisms in the young.

Total celectomy and massive small bowel resection in rats : S. Goto and J.L. Grosfeld. Eur J Pediatr Surg 1:24–26, (February), 1991

Total celectomy and massive small bowel resection in rats : S. Goto and J.L. Grosfeld. Eur J Pediatr Surg 1:24–26, (February), 1991

Total Colectomy and Massive Small Bowel Resection in Rats

Ileo- or jejuno-endorectal pull-through following total colectomy (TC) and massive small bowel resection (SBR) was performed in the rat to investigate the natural course of its condition. Animals were assigned to five experimental groups: TC only (n = 6), TC + 25% SBR (n = 6), TC + 50% SBR (n = 6), TC + 75% SBR (n = 6), and sham operation (SH) (n = 6). Survival at 28 days was 100% in groups TC and SH, while all rats receiving both TC and massive SBR eventually died within 14 days. Their number of survival days were 10.5 +/- 0.76 in group TC + 25% SBR*, 9.5 +/- 0.56 in group TC + 50% SBR*, and 5.8 +/- 0.48 in group TC + 75% SBR (*p less than 0.001 vs. group TC + 75% SBR). Changes in % of initial body weight revealed that the rats who received both TC and massive SBR showed a tremendous decrease of weight in the ensuing postoperative days and its degree was attributable to the extent of SBR. Our data support the clinical trials to preserve the aganglionic terminal ileum for the surgical treatment of extensive aganglionosis.