Parenteral but Not Enteral Omega‐3 Fatty Acids (Omegaven) Modulate Intestinal Regrowth After Massive Small Bowel Resection in Rats

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141380/1/jpen0503.pd

Dietary L-arginine supplementation reduces Methotrexate-induced intestinal mucosal injury in rat

<p>Abstract</p> <p>Background</p> <p>Arginine (ARG) and nitric oxide maintain the mucosal integrity of the intestine in various intestinal disorders. In the present study, we evaluated the effects of oral ARG supplementation on intestinal structural changes, enterocyte proliferation and apoptosis following methotrexate (MTX)-induced intestinal damage in a rat.</p> <p>Methods</p> <p>Male rats were divided into four experimental groups: Control rats, CONTR-ARG rats, were treated with oral ARG given in drinking water 72 hours before and 72 hours following vehicle injection, MTX rats were treated with a single dose of methotrexate, and MTX-ARG rats were treated with oral ARG following injection of MTX. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 72 hours following MTX injection. RT-PCR was used to determine bax and bcl-2 mRNA expression.</p> <p>Results</p> <p>MTX-ARG rats demonstrated greater jejunal and ileal bowel weight, greater ileal mucosal weight, greater ileal mucosal DNA and protein levels, greater villus height in jejunum and ileum and crypt depth in ileum, compared to MTX animals. A significant decrease in enterocyte apoptosis in the ileum of MTX-ARG rats (vs MTX) was accompanied by decreased bax mRNA and protein expression and increased bcl-2 protein levels.</p> <p>Conclusions</p> <p>Treatment with oral ARG prevents mucosal injury and improves intestinal recovery following MTX- injury in the rat.</p

Effect of dietary fat on fat absorption and concomitant plasma and tissue fat composition in a rat model of short bowel syndrome

The aim of this study was to investigate the effect of dietary fat on the time course of changes in fat absorption and tissue and plasma lipid composition in a rat model of short bowel syndrome (SBS). 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 three groups: Sham rats fed normal chow (Sham-NC), SBS rats fed normal chow (SBS-NC), or SBS rats fed a high-fat diet (SBS-HFD). Rats were sacrificed on day 3 or 14. Body weight, food intake, food clearance (dry fecal mass), and fat clearance (total fecal fat) were measured twice a week. Fat and energy intakes were calculated according to the amount of ingested food. Food and fat absorbability were calculated as intake minus clearance and were expressed as percent of intake. Serum cholesterol, triglyceride, and albumin were measured. Total lipid composition of the liver, epididymal adipose tissue, and the small intestine was determined. Statistical analysis was performed by a Student’s test, with p values <0.05 considered significant. Both food and fat absorbability diminished after bowel resection in rats fed NC. This was accompanied by a decrease in body weight gain, plasma triglyceride and protein levels, and total lipid content of the liver at day 3 and of a decrease in adipose tissue at day 14 following operation. SBS-HFD rats experienced a significant increase ( p <0.05) in food absorbability after 7 days and fat absorbability after 3 days compared with Sham-NC and SBS-NC rats ( p <0.05), as well as increases in serum cholesterol, triglycerides, and glucose compared with SBS-NC rats. On day 14, plasma lipid levels in SBS-HFD rats were not different from SBS-NC or control rats; however, albumin levels were higher. A high-fat diet increased total fat content of the liver early after operation. In conclusion, in a rat model of SBS, an early high-fat diet increased the absorptive capacity of the intestinal remnant as seen by increased food and fat absorbability. These findings suggest a benefit of a high-fat diet on intestinal adaptation in general and on lipid absorption in particular.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47161/1/383_2004_Article_1143.pd

Effect of dietary fat on early morphological intestinal adaptation in a rat with short bowel syndrome

Among factors promoting mucosal hyperplasia after bowel resection, long-chain fatty acids may have a special role. The purpose of the present study was to evaluate the effects of high-fat diet (HFD) on early intestinal adaptation in rats with short bowel syndrome (SBS). 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 three groups: Sham rats fed normal chow (Sham-NC); SBS rats fed NC (SBS-NC); and SBS rats fed HFD (SBS-HFD). Rats were killed on days 3 or 14. Body weight and parameters of intestinal adaptation (overall bowel and mucosal weight, mucosal DNA and protein, villus height, and crypt depth) were determined at time of killing. By day 3, SBS-HFD rats demonstrated higher duodenal and jejunal bowel and mucosal weights and ileal villus height and jejunal crypt depth vs SBS-NC rats. By day 14 SBS-HFD rats continued to demonstrate increased duodenal and jejunal bowel weight and duodenal mucosal weight vs SBS-NC animals. We conclude that early exposure to HFD both augmented and accelerated structural bowel adaptation in a rat model of SBS.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47163/1/383_2004_Article_1168.pd

The time relationship between ipsilateral testicular ischemia and germ cell apoptosis in the contralateral testis in rat

Unilateral testicular ischemia-reperfusion (IR) in the rat is followed by histologic damage in the contralateral testis, which has been previously explained on immunologic grounds. There is evidence to suggest that apoptosis in the contralateral testis is involved in germ cell loss following IR injury to the testis. We examined the time-dependent effect of testicular ischemia on germ cell apoptosis in the contralateral testis in a rat. Adult Sprague–Dawley rats weighing 250–280 g, were subjected to testicular ischemia for 1, 2, 3 or 24 h. Twenty-four hours following onset of the ischemic insult, testes were harvested for immunohistochemical studies. Apoptosis was detected using TUNEL immunohistochemical assay. Testicular ischemia in rats led to histological damage, which was related to the duration of the ischemia. In the contralateral testis, the minimal damage included a decrease in number of germ cell layers, mild disorganization, and single cell apoptosis. Apoptosis in the contralateral testes increased significantly after 2, 3, and 24 h of ischemia and showed direct, time-related correlation with the duration of ischemia. We conclude that testicular ischemia causes an increase in germ cell apoptosis in the contralateral testis. The extent of apoptosis increases with the duration of the ischemia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47174/1/383_2005_Article_1477.pd

Effect of diclofenac on germ cell apoptosis following testicular ischemia-reperfusion injury in a rat

Recent evidence suggests that enhanced cell apoptosis is responsible for germ cell loss following testicular ischemia-reperfusion (IR) injury. A nonsteroidal anti-inflammatory drug diclofenac sodium (Voltaren) is a prostaglandin-synthesis inhibitor, which is widely used in many testicular disorders. The purpose of the present study was to examine the effect of diclofenac (DIC) on germ cell apoptosis in the ischemic and contralateral testes following testicular IR in a rat. Forty rats were divided randomly into four experimental groups of ten rats each: group A (Sham)—Sham operated animals; group B (Sham-DIC)—Sham operated rats that were treated with DIC given subcutaneously at a dose of 10 mg/kg, once daily, 24, 48 and 72 h following operation; group C (IR) underwent 90 min of unilateral testicular IR; group D (IR-DIC)—rats underwent 90 min of unilateral testicular IR and were treated with DIC similarly to group B. Ninety-six hours following operation, the rats were sacrificed and testes were harvested. Johnsen’s criteria and the number of germinal cell layers were used to categorize the spermatogenesis. TUNEL assay was used to determine germ cell apoptosis in both the ischemic and contralateral testes. Statistical analysis was performed using the non-parametric Kruskal–Wallis ANOVA test, with P less than 0.05 considered statistically significant. Testicular ischemia in rats led to histological damage in the ipsilateral testis. In the contralateral testis, minimal damage was observed. Germ cell apoptosis in both the ischemic and the contralateral testes increased significantly after IR. Treatment with DIC did not change histologic parameters of spermatogenesis in both the ischemic and contralateral testes, but decreased germ cell apoptosis in both testes following testicular IR. We conclude that testicular ischemia causes an increase in germ cell apoptosis in the contralateral testis. Diclofenac may be beneficial for spermatogenesis following testicular IR by decreasing germ cell apoptosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47177/1/383_2005_Article_1580.pd

Effect of Elevated Intra-Abdominal Pressure on Portal Vein and Superior Mesenteric Artery Blood Flow in a Rat

Abstract Aim: Recent clinical experience suggests that minimal access portoenterostomy (the Kasai procedure) for biliary atresia leads to transplantation sooner, compared to the traditional open approach. It should be emphasized that elevated intra-abdominal pressure (IAP) may reduce hepatic and portal blood flow and thus may cause histologic liver damage. The aim of the present study was to evaluate the effects of IAP on blood flow in the portal vein (PV), compared to the superior mesenteric artery (SMA), and on the systemic mean arterial blood pressure (MABP). Materials and Methods: Male Sprague-Dawley rats were anesthetized with intraperitoneal ketamine (90 mg per kg) and xylasine (13 mg per kg). Polyethylene catheters (PE-50) were introduced into the right carotid artery for the measurement of MABP. After a midline laparotomy, the SMA and PV were isolated. Ultrasonic blood-flow probes were placed on the vessels for the continuous measurement of regional blood flow. Two large-caliber percutaneous peripheral intravenous catheters were introduced into the peritoneal cavity for inflation of air and for the measurement of IAP. The time course of MABP and SMA and PV flow as well as the relationship between IAP and SMA and PV flow were determined. Results: Although all three hemodynamic parameters decreased with the increase in the IAP, the most significant changes were observed in PV blood flow. IAP at 3 mm Hg resulted in a 26% decrease in PV flow (P < 0.05), a 19% decrease in SMA flow (P < 0.05), and an 11% decrease in MABP (P < 0.05). IAP at 6 mm Hg caused a two-fold decrease in PV flow (P < 0.05), a 30% decrease in SMA flow (P < 0.05), and a 19% decrease in MABP (P < 0.05). There were no changes in the time course of MABP and PV and SMA flow. PV and SMA flow returned to normal values immediately after abdominal deflation. Conclusions: Persistent IAP decreased MABP, SMA, and, especially, PV flow by 50%. We speculate that in biliary atresia patients with already present liver dysfunction, decrease in SMA flow and even a greater decrease in PV flow from increased IAP, which occurs during a laparoscopic Kasai procedure, may further compromise liver function. This may be one of the explanations for the progression to earlier transplantation in infants undergoing a laparoscopic Kasai procedure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78156/1/lap.2008.0145.supp.pd

Advances in short bowel syndrome: an updated review

Short bowel syndrome (SBS) continues to be an important clinical problem due to its high mortality and morbidity as well as its devastating socioeconomic effects. The past 3 years have witnessed many advances in the investigation of this condition, with the aim of elucidating the cellular and molecular mechanisms of intestinal adaptation. Such information may provide opportunities to exploit various factors that act as growth agents for the remaining bowel mucosa and may suggest new therapeutic strategies to maintain gut integrity, eliminate dependence on total parenteral nutrition, and avoid the need for intestinal transplantation. This review summarizes current research on SBS over the last few years.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47168/1/383_2005_Article_1500.pd

Effect of leptin on intestinal re-growth following massive small bowel resection in rat

Recent evidence suggests that the adipose tissue-derived cytokine leptin (LEP) is involved in modulation of growth and differentiation of normal small intestine. The purpose of the present study was to evaluate the effects of parenteral LEP on structural intestinal adaptation, cell proliferation and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection and re-anastomosis, SBS-rats underwent a 75% small bowel resection, and SBS-LEP-rats underwent bowel resection and were treated with LEP given subcutaneously at a dose of 20 μg/kg, once daily, from day 3 through 14. Parameters of intestinal adaptation (bowel and mucosal weights, mucosal DNA and protein, villus height and crypt depth in jejunum and ileum), enterocyte proliferation and enterocyte apoptosis were determined on day 15 following operation. Ileal tissue samples were taken for detection of bax and bcl-2 gene expression using RT-PCR technique. Statistical analysis was performed using the non-parametric Kruskal–Wallis ANOVA test, with P< 0.05 considered statistically significant. Treatment with subcutaneous LEP resulted in a significant increase in jejunal (17%, P< 0.05) and ileal (13%, P< 0.05) bowel weight, jejunal (10%, P< 0.05) and ileal (25%, P< 0.05) mucosal weight, jejunal (26%, P< 0.05) and ileal (38%, P< 0.05) mucosal DNA, ileal (25%, P< 0.05) mucosal protein, jejunal (41%, P< 0.05) and ileal (21%, P< 0.05) villus height, jejunal (37%, P< 0.05) crypt depth, and jejunal (24%, P< 0.05) and ileal (21%, P< 0.05) enterocyte proliferation compared to SBS-animals. Enterocyte apoptosis increased significantly after bowel resection in jejunum and ileum compared to sham animals and was accompanied by an increased bax gene expression and a decreased bcl-2 gene expression in ileal samples. SBS-LEP rats showed a trend toward a decrease in enterocyte apoptosis in ileum and a mild decrease in bax gene expression compared to SBS-untreated animals. In conclusion, in a rat model of SBS parenteral LEP stimulates structural intestinal adaptation. Increased cell proliferation and decreased cell death via apoptosis may be responsible for this increased cell mass.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47175/1/383_2005_Article_1572.pd