Parenteral omega-3 fatty acids (Omegaven) modulate intestinal recovery after intestinal ischemia-reperfusion in a rat model.

BACKGROUND/PURPOSE: Fatty acids from fish oil (omega-3 polyunsaturated fatty acids, 3PUFAs) are emerging as powerful yet safe disease-modifying nutrients and are protective in severe critical care conditions including ischemia-reperfusion (IR) injury. The purpose of the present study was to examine the effects of 3PUFAs on intestinal structural changes, enterocyte proliferation, and apoptosis after intestinal IR in a rat. METHODS: Male rats were divided into three experimental groups: sham rats underwent laparotomy, IR rats underwent occlusion of both superior mesenteric artery and portal vein for 30 minutes followed by 48 hours of reperfusion, and 3PUFA-treated IR (IR-3PUFA) rats underwent IR and were treated with Omegaven (Fresenius Kabi, Bad Homburg, Germany) given intraperitoneally at a dose of 1 mL twice a day. Intestinal structural changes (Park injury score, overall bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, cell proliferation, and apoptosis) were determined 48 hours after IR. Real-time polymerase chain reaction (PCR) was used to determine the level of bax and bcl-2 messenger RNA. RESULTS: A significant decrease in bowel and mucosal weight was observed in the ileum of untreated IR rats compared with sham animals. Forty-eight hours after IR, cell apoptosis remained increased in the jejunum and ileum, which coincided with increased bax/bcl-2 ratio. Cell proliferation was increased 48 hours after IR, suggesting tissue repair. Treatment with Omegaven resulted in a significant increase in bowel and mucosal weight in the jejunum and ileum, villus height in the jejunum and ileum, and crypt depth in the jejunum compared with untreated IR animals. IR-3PUFA rats also demonstrated a significantly lower Park injury score in the jejunum and ileum as well as a lower apoptotic index in the ileum compared with untreated IR animals. CONCLUSIONS: Parenteral Omegaven administration decreases the intestinal mucosal injury and inhibits enterocyte apoptosis after intestinal IR in a rat.

Effect of oral insulin on diabetes-induced intestinal mucosal growth in rats.

BACKGROUND: To evaluate the intestinal response to the induction of diabetes and to oral insulin (OI) administration in a rat. METHODS: Male Sprague-Dawley rats were divided into four experimental groups: control rats, CONTR-INS rats that were treated with OI given in drinking water for 7 days, diabetic rats that were injected with one dose of streptozotocin, and diabetic rats treated with OI. Intestinal structural changes, enterocyte proliferation and enterocyte apoptosis, bax and bcl-2 mRNA and protein levels, insulin receptor expression and ERK protein levels were determined at sacrifice. A one-way ANOVA for comparison, followed by Tukey's test for pair-wise comparison, were used for statistical analysis. RESULTS: Induction of diabetes resulted in a significant increase in bowel and mucosal weight (P < 0.05), mucosal protein (P < 0.05), villus height and crypt depth in jejunum and ileum (P < 0.05), and mucosal DNA in ileum (P < 0.05) (vs. control animals). Diabetes also enhances ERK-induced cell proliferation (P < 0.05) and concomitant bax/bcl-2 induced cell apoptosis (P < 0.05). Treatment of diabetic rats with OI resulted in a significant decrease in jejunal protein content (P < 0.05), jejunal and ileal villus height (P < 0.05), and jejunal crypt depth (P < 0.05), as well as an inhibition of ERK-related cell proliferation in ileum (P < 0.05). Expression of insulin receptor was down-regulated following OI administration in both control and diabetic animals. CONCLUSIONS: Experimental STZ-induced diabetes causes intestinal mucosal growth and enhances enterocyte turnover in a rat model. OI administration diminishes diabetes-accelerated cell turnover and diabetes-induced mucosal hyperplasia.

Nutritional supplementation with transforming growth factor-beta inhibits intestinal adaptation after massive small bowel resection in a rat.

INTRODUCTION: Transforming growth factor beta (TGF-ß) has been shown to affect epithelial cell differentiation and proliferation through epithelial-mesenchymal and epithelial-immune cell interaction. In the present study, we evaluated the effect of TGF-ß2-enriched polymeric diet (Modulen) on enterocyte turnover in a rat model of short bowel syndrome (SBS). METHODS: Male rats were divided into four groups: Sham rats and Sham-TGF-ß rats underwent bowel transection, and were treated with TGF-ß from the 4th postoperative day, SBS rats underwent a 75% bowel resection, and SBS-TGF-ß rats underwent bowel resection and were treated with TGF-ß-enriched diet similar to Group B. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined on day 15. Real-time PCR was used to determine Bax and Bcl-2 mRNA expression. RESULTS: Treatment of SBS animals with TGF-ß2 supplemented diet led to a significant decrease (vs. SBS rats) in bowel weight in ileum (18%, P < 0.05), mucosal DNA content in jejunum (threefold decrease, P < 0.05) and ileum (2.5-fold decrease, P < 0.05), and mucosal protein in jejunum (twofold decrease, P < 0.05) compared to SBS-untreated animals (Group B). Treatment with TGF-ß resulted in a mild decrease in enterocyte proliferation in jejunum (25%, P < 0.05) and ileum (18%, P < 0.05). A decreased cell apoptosis in the SBS-TGF-ß group was accompanied by a decreased Bax and increased Bcl-2 mRNA expression. CONCLUSIONS: In a rat model of SBS, dietary TGF-ß inhibits intestinal adaptation. Decreased enterocyte proliferation is responsible for this effect.

Parenteral but not enteral omega-3 fatty acids (Omegaven) modulate intestinal regrowth after massive small bowel resection in rats.

BACKGROUND: The purpose of the present study was to evaluate the effects of ω-3 fatty acids (Omegaven) on early intestinal adaptation in rats with short bowel syndrome (SBS). METHODS: Male Sprague-Dawley rats were randomly assigned to 1 of 4 groups: sham rats underwent bowel transection; SBS rats underwent 75% bowel resection; SBS-O ω-3 rats underwent bowel resection and were treated with oral Omegaven given by gavage; and SBS-I ω-3 rats underwent bowel resection and were treated with Omegaven given intraperitoneally. Rats were killed on day 14. Parameters of intestinal adaptation (bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depths, cell proliferation and apoptosis) were determined at time of death. Real-time polymerase chain reaction was used to determine the level of Bax and Bcl-2 messenger RNA (mRNA). Statistical analysis was performed using Kruskal-Wallis test followed by post hoc test, with P < .05 considered statistically significant. RESULTS: Oral ω-3 supplementation did not significantly change intestinal regrowth. In contrast, parenteral ω-3 in rats that underwent resection resulted in higher bowel and mucosal weights, mucosal DNA and protein in ileum, villus height in ileum, crypt depth in jejunum and ileum, and greater rates of cell proliferation in jejunum and ileum compared with SBS animals. The initial decreased levels of apoptosis corresponded with the early decrease in Bax and increase in Bcl-2 mRNA levels. CONCLUSIONS: Parenteral but not enteral Omegaven augments and accelerates structural bowel adaptation in a rat model of SBS. Increased cell proliferation and decreased apoptosis reflect increased cell turnover in Omegaven-treated animals.

The yield of a continuously patent gastroesophageal junction during upper endoscopy as a predictor of esophagitis in children.

BACKGROUND AND AIMS: Over the last years we have noted an association between the endoscopic finding of a continuously patent gastroesophageal junction (GEJ) throughout the procedure and macroscopic or microscopic esophagitis. We could not find documentation for these endoscopic findings as a predictor of esophagitis in the literature. We aimed to find an association between these findings and microscopic and macroscopic esophagitis. METHODS: During upper endoscopy, we routinely observe the GEJ for about 60 s and note the behavior of the GEJ and esophageal contractions. Patients with a persistently patent GEJ were recorded. A group of patients referred for upper endoscopy for reasons other than suspected reflux, whose esophagus was normal, and patients with reflux symptoms served as a control groups. RESULTS: We found 21 patients (3.0%) in whom a patent GEJ had been noted. No significant age differences were noted between study and control groups. Eighteen out of 21 patients (86%) in the study group had varying degrees of microscopic esophagitis ranging from mild to severe (ten with mild esophagitis, three with moderate esophagitis, and five with severe esophagitis). Interestingly, ten out of 18 (55%) study patients with esophagitis on biopsies had no evidence of additional esophageal abnormality. Although all control patients had a normally appearing esophagus on upper endoscopy, 8/26 (31%) had mild esophagitis on biopsies. Differences were statistically significant (p < 0.001). CONCLUSIONS: A continuously patent GEJ predicts quite accurately the presence of esophagitis in biopsies and may serve an additional endoscopic finding for the diagnosis of esophagitis especially non-erosive GER.

Effect of simvastatin on intestinal recovery following gut ischemia-reperfusion injury in a rat.

BACKGROUND: Pleiotropic (lipid lowering-independent) effects of statins are attributed to their antiinflammatory, antioxidant, and/or vascular actions. Extensive studies in various experimental models have established that pretreatment with simvastatin significantly protects heart and kidney injured by ischemia-reperfusion (IR). The purpose of the present study was to examine the effect of simvastatin on intestinal recovery and enterocyte turnover after intestinal IR injury in rats. METHODS: Male Sprague-Dawley rats were divided into three experimental groups: (1) sham rats underwent laparotomy, (2) IR-rats underwent occlusion of both superior mesenteric artery and portal vein for 30 min followed by 48 h of reperfusion, and (3) IR-SIM rats underwent IR and were treated with oral simvastatin (10 mg/kg) given by gavage immediately before and 24 h after operation. Intestinal structural changes, Park's injury score, enterocyte proliferation and enterocyte apoptosis were determined 24 h following IR. A non-parametric Kruskal-Wallis ANOVA test was used for statistical analysis with P less than 0.05 considered statistically significant. RESULTS: Treatment with simvastatin resulted in a significant increase in bowel and mucosal weight in ileum, villus height and crypt depth in jejunum and ileum compared to IR animals. IR-SIM rats had also a significantly lower intestinal injury score as well as lower apoptotic index in jejunum and ileum compared to IR animals. CONCLUSIONS: Treatment with simvastatin prevents gut mucosal damage and inhibits programmed cell death following intestinal IR in a rat.

Dietary palmitic acid modulates intestinal re-growth after massive small bowel resection in a rat.

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.