Intestinal disaccharidase activity following pancreatic duct occlusion in the rat

The influence of pancreatic secretions on growth and brush-border enzyme activity, throughout the entire small intestine, was examined in the rat. Pancreatic secretions were excluded from the gut lumen by stapling the pancreatic ducts, without interruption of bile flow. The entire small intestine was studied as four segments; the duodenum and three distal segments of equal length. Weight of intestine and mucosa, and mucosal sucrase, isomaltase, lactase, and alkaline phosphatase activity were measured 10-15 days following pancreatic duct occlusion, or sham-operation. The duodenum of pancreatic duct-occluded animals exhibited significant hypertrophy. In general, specific and total disaccharidase activities were greater in duct-occluded animals than in controls throughout the intestine. The increase was more pronounced in distal than in proximal segments. The sucrase/isomaltase ratio was significantly greater in pancreatic duct-occluded animals than in controls in the two distal segments. Alkaline phosphatase activity was not affected by pancreatic duct occlusion. The greater relative increase of disaccharidase activities and sucrase/isomaltase activity ratios in the distal segments of duct-occluded animals, indicates a more important regulatory role of pancreatic enzymes in the distal small intestine. It is concluded that regulation of intestinal brush-border enzyme activity by pancreatic secretion is selective for enzyme and site as follows: disaccharidases, but not alkaline phosphatase, are regulated; the sucrase subunit of the sucrase/isomaltase complex is most sensitive to regulation, while lactase is least sensitive; and the regulatory effect on disaccharidases is greater in distal than in proximal intestine.     

Age related increase of brush border enzyme activities along the small intestine.

Intestinal morphology and brush border hydrolase activities were determined along the small intestine of young adult (three months, n = 10), mature (12 months, n = 10), and senescent (29 months, n = 15) rats. The intestinal segments of the senescent rats contained higher mucosal mass and protein content (p less than 0.05) compared with the young and mature animals. A significant reduction of villus height and crypt depth (p less than 0.05) was found in the proximal intestine during aging. A 35% increase in villus height (p less than 0.05) without changes in crypt depth, was observed in the distal ileum in senescent rats. The activities of sucrase and isomaltase were significantly increased during aging in the duodenum and jejunum (p less than 0.05). Lactase and aminopeptidase activities which showed only minor changes between young and mature animals were significantly enhanced in senescent animals (p less than 0.05) with aminopeptidase exhibiting a three-fold increase in activity in the proximal ileum. The results when combined with those of previous studies suggest that in the aged animal, the increased level of intestinal hydrolase activities may be the consequence of prolonged cellular maturation along the villi in the proximal intestine, and of adaptation to increased concentrations of intraluminal substrates in the distal intestine.     

Glucagon-like Peptide-2 Induces a Specific Pattern of Adaptation in Remnant Jejunum

Glucagon-like peptide-2 (GLP-2) is an enteroendocrine hormone which is uniquely trophic for the intestine; a physiological role in regulating nutrient absorptive capacity is becoming apparent. GLP-2, independent of enteral feeding, stimulates a classical pattern of intestinal adaptation in terminal ileum following resection. Herein we investigate the effects of GLP-2 on the jejunal remant using a rat model of short bowel syndrome (SBS). Juvenile 250- to 275-g SD rats underwent 80% distal small bowel resection, leaving 20 cm of proximal jejunum and venous catheterization. Animals were maintained with total parenteral nutrition (TPN) or TPN+10 μg/kg/hr GLP-2 (n=8 per group). After 7 days, intestinal permeability was assessed by urinary recovery of gavaged carbohydrate probes. Animals were euthanized, and the intestines taken for analysis of morphology, crypt cell proliferation, apoptosis, and expression of SGLT-1 and GLUT-5 transport proteins. GLP-2 treatment reduced intestinal permeability and increased in vivo glucose absorption, small intestinal weight, surface area, villus height, crypt depth, and microvillus height. Intestinal mucosal DNA and protein content per unit length of the small bowel were increased (P < 0.05 for all comparisons). However, in contrast to previous studies examining GLP-2’s effects on remnant ileum, the jejunal crypt apoptotic index was increased in GLP-2-treated animals, with no increase in SGLT-1 or GLUT 5 expression. These results show that exogenous GLP-2 treatment of animals with jejunal remnant reduces intestinal permeability, increases glucose absorption, and stimulates morphological features of intestinal adaptation including increased micovillus height and surface area. However, the pattern of changes seen is different from that in remnant ileum. This suggests that GLP-2’s effects are specific to different regions of the bowel. Nonetheless, remnant jejunum is responsive to GLP-2 in the absence of enteral nutrition. Further studies are warranted to establish the mechanisms of action and therapeutic potential of GLP-2 in modulating nutrient absorptive capacity.     

Effect of interleukin-11 on ameliorating intestinal damage after methotrexate treatment of breast cancer in rats

Gastrointestinal mucositis after cancer chemotherapy is an increasing problem that is essentially untreatable once established, although it gradually remits. The aim of this study was to investigate the time-course and effect of interleukin-11 (IL-11) on apoptosis and intestinal morphometry as measures of mucositis. Female DA rats were implanted subcutaneously with syngeneic breast cancer and treated with methotrexate (MTX). Intestinal morphometry was used to assess villus area, crypt length, and mitotic count per crypt. Apoptosis was assessed by TUNEL assay in the tumor and jejunum. Tumor proliferation was assessed by mitotic count. The time-course study showed that MTX increased apoptosis by 28-fold in the crypts of the small intestine and by 3-fold in the tumor, and peaked at 6 hr after chemotherapy. IL-11 (100 g/kg/ twice daily subcutaneously) maintained intestinal weight, and reduced the severity of mucositis, as measured by villus area, crypt length, and mitotic count per crypt. IL-11 at higher doses (200 g and 400 g/kg/twice daily subcutaneously), did not further improve villus area, crypt length, and mitotic count per crypt. IL-11 did not affect tumor apoptosis or proliferation. We conclude that IL-11 attenuated mucositis by maintaining intestinal weight and morphometry. IL-11 did not prevent apoptosis, but rather induced compensatory crypt cell proliferation.     

Morphological and functional adaptation of the small intestine after colectomy and ileal pouch-anal anastomosis in rats

BACKGROUND AND AIMS: This study investigated morphological and functional changes in the small bowel after colectomy and ileal pouch-anal anastomosis (IPAA). METHODS AND MATERIALS: In 15 rats electrolyte, glucose, and water absorption was determined by in vivo single-pass perfusion of the proximal and distal small intestine 15 weeks after IPAA. Afterwards the small intestine was resected for morphometric evaluation. Controls were 15 identically treated rats without operation. RESULTS: IPAA led to a significant increase in the small intestinal diameter and a significant increase in villus length and density, which was more apparent in ileum than in jejunum. Therefore the mucosal surface per unit serosa increased significantly by 59% in the jejunum and by 76% in the ileum. In the pouch there was a significant increase in goblet cell density, crypt depth, and diameter of the muscularis which was not detectable in the segments proximal from the pouch. Due to the increase in mucosal surface there was a significant increase in total glucose and electrolyte and sorption in the ileum while absorption rates per unit mucosa were unchanged, with the exception of an increase in mucosal sodium absorption. Jejunal absorption and ileal absorption of water remained unchanged. CONCLUSION: Adaptation of the small intestine after IPAA leads to colonic metaplasia in the pouch and intestinal hyperplasia proximal from the pouch. The loss of colonic absorption is compensated by the increase in ileal mucosal surface with subsequently elevated electrolyte and glucose absorption. Changes in intestinal permeability may be responsible for additional water depletion, which is compensated by the upregulation of enteric water and sodium absorption.     

Restoration of colorectal continuity reverses atrophy in human rectal mucosa

Cell kinetic activity and adaptive response of rectal mucosa from patients with Hartmann's procedure were studied before and after restoration of colorectal continuity. Patients without colostomy and with normal rectal mucosa were used as controls. Autoradiography ofin vitro labeled mucosal samples with [³H]thymidine was used. The proliferative activity in the rectal crypts was estimated by measuring labeling and mitotic indices, total DNA of isolated crypts, and total crypt cell numbers. One hundred forty days after creating a proximal end colostomy, labeling index (P<0.05), mitotic index (P<0.01), DNA content per crypt (P<0.05), and number of cells per crypt (P<0.05) decreased significantly compared to control values. Restoration of colorectal continuity resulted in a significant increase of the labeling index (P<0.05), the mitotic index (P<0.07), the DNA content per crypt (P<0.05), and the cell number per crypt (P<0.05). There were no significant differences between the postclosure values and the controls. These data indicated that excluding the human rectal mucosa from fecal stream determined a mucosal atrophy that could be reversed by restoration of colorectal continuity.     

Pancreatic polypeptide release by intraluminal fatty acids

The question of whether the response of pancreatic polypeptide to intestinal fatty acids is influenced by the site of intestinal perfusion or the chain length of the fatty acid was investigated. Six dogs with chronic gastric, pancreatic, and intestinal fistulas were studied. Proximal perfusates were administered at the pylorus and diverted via a Foley catheter in the orad stoma of an intestinal fistula placed 45 cm beyond the pancreatic cannula. Distal perfusates were administered into the caudal stoma of the intestinal cannula. Three experimental protocols were used: proximal fatty acid perfusion (20, 40, or 80 mmol/L) combined with distal saline perfusion; distal fatty acid perfusion (20, 40, or 80 mmol/L) combined with proximal saline perfusion; or distal fatty acid perfusion combined with proximal fatty acid perfusion of 80 mmol/L. Each dose of fatty acid was given in random order and the two fatty acids (dodecanoate and oleate) were tested on different days. Blood samples were drawn for pancreatic polypeptide radioimmunoassay, and pancreatic secretion was collected for determination of bicarbonate and protein outputs. Pancreatic polypeptide responses to perfusion of both proximal and distal segments with oleate exceeded (P < 0.05) those evoked by dodecanoate. The responses of pancreatic polypeptide to dodecanoate administration into either the proximal segment or the distal intestine were not significantly different. In contrast, perfusion of the proximal intestinal segment with oleate released significantly (P < 0.05) less pancreatic polypeptide than did distal intestinal perfusion with oleate. It is concluded that oleate is a more potent stimulus of canine pancreatic polypeptide release than is dodecanoate and that maximal pancreatic polypeptide release in response to intestinal oleate can be achieved even if the proximal 45 cm segment of intestine is excluded.     

Analysis of the effects of food and of digestive secretions on the small intestine of the rat. 1. Mucosal morphology and epithelial replacement.

A modified Roux-en-Y repositioning of rat small intestine was performed so that the proximal segment of bowel (A) received only bile and pancreastic secretions, the second (B) received food direct from the stomach, and these two segments drained into a third (C). Four to five weeks after operation, cell production was assessed by injection of vincristine into operated, sham-operated and unoperated rats, and counts of blocked metaphases were made on isolated microdissected crypts. Villus height, crypt depth, and the number of crypts per villus (crypt/villus ratio) were also measured. Most of segment A showed no significant differences from sham-operated intestine, although the normal proximo-distal gradient of villus height was abolished. At the distal end (near the anastomosis with segments B and C), crypt depth and cell production were increased. The villus height gradient in segment B was also abolished, although crypt depth and cell production were significantly increased, especially at the proximal end. Crypt/villus ratio was also increased. Segment C showed all the characteristics of small bowel promoted to a more proximal position: increased villus height, crypt depth and cell production. Increased crypt/villus ratio was also observed. These results are discussed in terms of the role of food and of digestive secretions in the control of mucosal morphology and epithelial replacement.     

Induction of pancreatic tumours by longterm duodenogastric reflux.

The incidence of pancreatic cancer is increased in patients who have undergone gastric surgery. An animal model is described in which pancreatic hyperplasia and adenoma formation developed within 56 weeks. The effects of a simple gastrojejunostomy were compared with those after a split gastrojejunostomy, in which the jejunum was transected and the two limbs implanted separately into the greater curvature of the glandular stomach 1 cm apart. After 56 weeks no animals in the simple gastrojejunostomy group had pancreatic hyperplasia whereas all 10 animals in the split gastrojejunostomy group had generalised pancreatic hyperplasia with macroscopic nodules. Microscopy of the nodules showed that in nine animals hyperplastic nodules had developed, and four of these also had adenomatous nodules. The remaining animal had enlarged lymph nodes. Pancreatic hyperplasia was associated with jejunal hyperplasia. Jejunal morphometry showed that the villus height was doubled and the villus height:crypt depth ratio was higher in the split gastrojejunostomy group compared with those animals with a simple gastrojejunostomy. This finding represents a new model for the investigation of pancreatic neoplastic change.     

Origin and characterization of migrating myoelectric complex in rabbits

Myoelectric activity patterns of the upper gastrointestinal tract were recorded using chronically implanted electrodes in conscious rabbits. A cyclical pattern of intense spiking activity occurring on almost every slow wave for 10-15 min, corresponding to the regular spiking phase or phase III of the migrating myoelectric complex (MMC), was recorded. This activity was detected by electrodes implanted distal to the ligament of Treitz on the proximal jejunum at a frequency of 9.4-10.6/24 hr. The MMC pattern occurred in both fed and fasted animals, regardless of the presence of cecotrophy. Initiation of phase III activity on the jejunum persisted after transplantation of the pancreatic duct opening to the proximal duodenum 5 cm from the pylorus and when gastric contents emptied directly into the proximal jejunum through a large gastrojejunostomy. It is concluded that the MMC pattern of the rabbit small intestine is persistently initiated in the proximal jejunum distal to the pancreatic and biliary ducts. The jejunal origin of the MMC in the rabbit is reminiscent of that seen transiently 8-10 hr after a meal in dogs during the change from fed to the fasted pattern of gastrointestinal motor activity.     

The effect of bicarbonate and acidification on water and electrolyte absorption by the intestine of normal and infected (Hymenolepis diminuta: Cestoda) rats

The jejunum, proximal, and distal ileum of both uninfected and parasitized rats (Hymenolepis diminuta: Cestoda) were perfusedin vivo with saline solutions differing in hydrogen ion and bicarbonate concentration. In the jejunum and proximal ileum of both the parasitized and uninfected animals the luminal fluid was acidified via a hydrogen-ion secretory mechanism; similarly in the infected distal ileum.Hymenolepis diminuta further acidified the intestinal lumen by secreting hydrogen ions. The presence of bicarbonate stimulated absorption of sodium, bicarbonate, and fluid in the uninfected jejunum, in all the regions of the infected intestine, and also by the parasites. This accelerating effect of bicarbonate was pH-sensitive and it is considered to be of questionable importance in the acidic postprandial proximal intestine. Lowering the pH of the luminal fluid diminished intestinal absorption of salt and water, or caused a net secretion of isotonic fluid; the distal ileum was less sensitive to the pH changes. Water and electrolyte absorption byHymenolepis diminuta was stimulated by low luminal pH, but absorption in all three regions of the infected small intestine was diminished, due either to reduced absorption or enhanced secretion.This work is part of a thesis which will be submitted by the senior author to the University of Toronto in partial fulfillment of the requirements for the degree of Doctor of Philosophy. The award of a National Research Council of Canada Scholarship is gratefully acknowledged. This work was supported by the National Research Council of Canada, through Grant No. A4667 to D.F. Mettrick.     

Morphological study of the small intestine in rats with experimental zinc deficiency

Rats were maintained 4 weeks on a zinc deficient diet from the time of weaning. A control group received the same basic diet supplemented with zinc. Zinc deficiency, was indicated by poor weight gain, diarrhea, exudative vesicular dermatitis around ears, eyes, nose and extremities, and lowering of blood zinc levels. The morphometric study of the small intestine showed: 1) decreased thickness of the intestinal wall and of the mucosa; 2) significant decrease of the mean villies length and of the mean crypt depth; 3) no alterations in the height of the enterocytes from the middle one third of the villis and in the number of Paneth cells; 4) a decreased mitotic index; 5) a diminished number of epithelial cells living the ville, and 6) a decreased population of intraepithelial lymphocytes, both in the proximal jejunum and distal ileum. These findings are compatible with an impairment of cell replication in the small intestine in experimental zinc deficiency in rats, and allow us to speculate that the diarrhea usually seen in states of zinc malnutrition, at least in part, could be dependent on these changes.     

Altered controls of proliferation in proximal small intestine of the senescent rat.

The proximal small intestine responds to starvation by rapidly reducing crypt cell proliferation rate and villus cellularity and to resumption of food intake (refeeding) by abruptly increasing proliferation and the number of villus epithelial cells. We show that villus cellularity responds to starvation and refeeding similarly in young and aging animals. However, as compared to young animals, senescent rats showed increased basal DNA synthetic activity, starvation resulted in a smaller decrease in DNA labeling of crypt cells, and refeeding produced an abrupt broadening of the proliferative zone in older animals without concomitant increased numbers of villus cells. Such altered crypt proliferative responses resemble precancerous changes seen in the colon and the aberrant proliferation found in both small and large intestine after administration of the carcinogen dimethylhydrazine.     

Postoperative morbidity and mortality after pancreatoduodenectomy with pancreatic duct occlusion compared to pancreatic anastomosis: a systematic review and meta-analysis

BackgroundPancreatoduodenectomy is burdened by elevated postoperative morbidity. Pancreatic duct ligation or occlusion have been experimented as an alternative to reduce the insurgence of postoperative pancreatic fistula. The aim of this systematic review and meta-analysis was to compare postoperative mortality and morbidity (pancreatic fistula, postoperative hemorrhage, delayed gastric emptying, pancreatic exocrine insufficiency and diabetes mellitus) between patients undergoing pancreatic anastomosis or pancreatic duct ligation/occlusion after pancreatoduodenectomy.MethodsA systematic review and meta-analysis of 13 studies was conducted following the PRISMA guidelines and the Cochrane protocol (PROSPERO ID: CRD42021249232).ResultsNo difference in postoperative mortality was highlighted. Pancreatic anastomosis was found to be protective considering all-grades pancreatic fistula (RR: 2.38, p = 0.0005), but pancreatic duct occlusion presented a 3-folded reduced risk to develop “grade C” pancreatic fistula (RR: 0.36, p = 0.1186), although not significant. Diabetes mellitus was more often diagnosed after duct occlusion (RR: 1.61, p < 0.0001); no difference was found in terms of pancreatic exocrine insufficiency (RR: 1.19, p = 0.151).ConclusionPostoperative mortality is not influenced by the pancreatic reconstruction technique. Pancreatic anastomosis is associated with a reduction in all-grades pancreatic fistula. More high-quality studies are needed to clarify if duct sealing could reduce the prevalence of “grade C” fistula.     

Transgenic mice that overexpress the human trefoil peptide pS2 have an increased resistance to intestinal damage.

pS2 is a member of the trefoil peptide family, all of which are overexpressed at sites of gastrointestinal injury. We hypothesized that they are important in stimulating mucosal repair. To test this idea, we have produced a transgenic mice strain that expresses human pS2 (hpS2) specifically within the jejunum and examined the effect of this overexpression on proliferation and susceptibility to indomethacin-induced damage. A transgenic mouse was produced by microinjecting fertilized oocytes with a 1.7-kb construct consisting of rat intestinal fatty acid binding protein promoter (positions -1178 to +28) linked to full-length (490 bp) hpS2 cDNA. Screening for positive animals was by Southern blot analysis. Distribution of hpS2 expression was determined by using Northern and Western blot analyses and immunohistochemical staining. Proliferation of the intestinal mucosa was determined by assessing the crypt cell production rate. Differences in susceptibility to intestinal damage were analyzed in animals that had received indomethacin (85 mg/kg s.c.) 0-30 h previously. Expression of hpS2 was limited to the enterocytes of the villi within the jejunum. In the nondamaged intestine, villus height and crypt cell production rate were similar in transgenic and negative (control) litter mates. However, there was a marked difference in the amount of damage caused by indomethacin in control and transgenic animals in the jejunum (30% reduction in villus height in controls vs. 12% reduction in transgenic animals, P < 0.01) but the damage sustained in the non-hpS2-expressing ileal region was similar in control and transgenic animals. These studies support the hypothesis that trefoil peptides are important in stimulating gastrointestinal repair.     

Induction and maintenance of mucosal enterokinase activity in proximal small intestine by a genetically determined response to mediated sodium transport

Mucosal enterokinase activity was established at intervals throughout the small intestine in guinea-pigs; maximum activity was present in the duodenum and proximal jejunum in new born as well as adult animals. Transposition of 5 cm lengths of small gut from the high enterokinase containing proximal region to the distal intestine and vice versa showed that mucosal enterokinase activity in the transposed segments was little changed after several weeks of healthy life. Isolation of proximal jejunal loops from luminal continuity resulted in the fall of mucosal enterokinase activity to minimal levels within 16 hours. Low levels of mucosal enterokinase activity were identified in loops of both proximal and distal jejunum 12 weeks after isolation. Luminal perfusion studies in vivo in proximal jejunal loops 24 hours after isolation showed that mucosal enterokinase activity could be restored to near normal levels within four to six hours by luminal sodium in the presence of active pancreatic endopeptidases, oligopeptides, L-amino acids, or D-glucose but not D-amino acids or D-fructose. Near normal mucosal enterokinase activity persisted in the loops for as long as luminal perfusion with 144 mM sodium and L-lysine or trypsin was maintained (24 hours). The time course of the restoration of mucosal enterokinase activity was compatible with an initial precursor activation as well as biosynthesis. The requirement for luminal sodium appeared to be absolute regardless of the co-substrate and supports the conclusion that mucosal enterokinase activity is dependent on mediated sodium transport. The ability of proximal intestinal enterocytes to respond to sodium flux with an increase in enterokinase activity is a property determined in intrauterine life: distal intestinal enterocytes may have functioning structural genes for enterokinase but appear to be unable to respond.     

Distribution of immunoreactive alkaline phosphatase in the adult rat ileum by immunoperoxidase staining at the light microscopic level

Our prior immunocytochemical studies using monospecific antibody to alkaline phosphatase, Bouin's fixation, and paraffin sections demonstrated a decreasing gradient of villus brush border staining from the proximal to the distal rat small intestine. In addition, we noted an unusual pattern of staining in the terminal centimeter of the adult rat ileum: the villus brush border staining was less intense than crypt brush border staining. To determine whether this pattern of staining was present throughout the entire ileum, we examined alkaline phosphatase staining in two separate jejunal sites and the entire lowest third of the intestine of adult Wistar rats. With Bouin's fixation and paraffin embedding, both conventional and germ-free rats showed the same unusual staining pattern throughout the entire ileum. This pattern suggested that bacterial proteases were not responsible for the diminished ileal brush border alkaline phosphatase. However, when acetone fixation and cryostat sections were used with the avidin-biotin-peroxidase complex system, the previously noted reversed gradient of staining between the ileal villus and crypt areas was no longer present. Rather, ileal crypt brush border staining was less than ileal villus brush border staining. With either methodology, jejunal villus brush border staining was significantly more intense than ileal brush border staining, whereas the deep crypt brush border staining was not significantly different between the two regions. The present study reinforces the need for a combination of methodologies in order to best and most accurately localize certain antigens with immunocytochemistry. It also confirms a decreasing proximal to distal gradient for villus brush border alkaline phosphatase despite similar deep crypt brush border staining throughout the small intestine.     

Effect of phytohemagglutinins on cell proliferation of the small intestine epithelium of rats]

Twenty male rats, were divided into two groups of ten animals each: E group, which received solid diet containing 4% of phytohemagglutinin and P group iso-caloric par-fed control, which received the same diet but the phytohemagglutinin was inactivated by heat. Water was offered ad libitum to all groups. The animals were weighed every day and the consumption of diet and water was registered. In the fourteenth day of experiment, the animals were sacrificed and the fragments of jejunum and ileum were removed to morphokinetic study. The results showed that the hydric ingestion was the same in both groups, the body weight of the E group was significant smaller than P group, the villus cell population from the jejunum of the E group was statistically smaller than P group and the contrary happened with ileum samples, wherein the E group was statistically larger than P. The jejunum villus height from E group was similar with P group, but in the ileum of the E group was larger than P. The depth, the cell population and cell production rate of crypt of E group were larger than P, in the jejunum and in the ileum. In conclusion, these results in the present study supply evidence that the intake of the phytohemagglutinin provokes injury of jejunal mucosa, reducing the villus cell population and stimulating the crypt hyperplasia, developing local adaptation. This adaptative model is similar to the one that occurs in celic disease. This proximal lesion stimulate crypt-villus unit hyperplasia of the ileal epithelium, developing distal adaptation. These adaptations occurred in animals that ingested phytohemagglutinin, even though with multicarencial malnutrition.     

Oral Insulin Up-regulates Toll-like Receptor 4 Expression and Enhances Intestinal Recovery Following Lipopolysaccharide-induced Gut Injury in a Rat

In the present study, we evaluated the protective effect of oral insulin (OI) on intestinal mucosa following lipopolysaccharide-induced intestinal damage in a rat. Male Sprague-Dawley rats were divided into three experimental groups: Sham rats, LPS-rats that were treated with lipopolysaccharide (LPS), and LPS-INS rats that were treated with OI given in drinking water 72 h before and following injection of LPS. Intestinal structural changes, enterocyte proliferation, enterocyte apoptosis, and mucosal expression of Toll-like receptor 4 (TLR4) were determined 24 h after the last LPS injection. LPS-INS animals showed a significantly greater bowel and mucosal weight in jejunum and ileum, mucosal DNA and protein in jejunum and ileum, villus height in ileum, crypt depth in jejunum and ileum, cell proliferation rates in jejunum, and significantly lower apoptotic index in ileum compared to LPS- animals. LPS rats demonstrated 50% increase in TLR4 expression in jejunum compared to sham animals. Treatment with OI resulted in a three-fold increase in TLR4 expression in jejunum, compared to LPS animals. In conclusion, OI improves intestinal recovery after LPS endotoxemia in a rat.