Tsuyoshi Nakamura

Medium-chain triglycerides modulate ileitis induced by trinitrobenzene sulfonic acid

Background : It is important to develop an appropriate animal model for further investigation into inflammatory bowel disease (IBD). We therefore investigated a trinitrobenzene sulfonic acid (TNBS) ileitis model. Dietary fat in Crohn’s disease is still a controversial risk factor for IBD. We therefore also studied the effects of medium‐chain triglycerides (MCT) and long‐chain triglycerides (LCT) on TNBS ileitis.

Medium-chain triglyceride-rich enteral nutrition is more effective than low-fat enteral nutrition in rat colitis, but is equal in enteritis

Background. Although enteral nutrition (EN) therapy for Crohns disease has been confirmed to be as effective as steroid therapy, the precise mechanism responsible for the effects of EN remains unclear, although some of the therapeutic effects of EN are believed to be due to a low dietary fat content. In order to elucidate the influence of fat in EN, it is important to investigate not only the quantity of fat, but also the source of the fat. Methods. We compared two enteral nutritional formulae: Elental (Ajinomoto) (elemental diet; ED), which contains only 1.5% fat, provided as long-chain triglycerides (LCT), versus Twinline (Snow Brand Milk Products) (TL), which contains a high percentage of fat (20.4%), provided mainly as medium-chain triglycerides (MCT). These formulae were tested on rat enteritis and rat colitis induced by trinitrobenzene sulfonic acid (TNBS). Results. Both ED and TL reduced the manifestations of enteritis. TL had a stronger anti-inflammatory effect than ED for colitis. TL also had nutritional advantages as compared with ED, as shown by the total serum protein in the TL group being significantly higher than that in the ED group. Conclusion. The results indicate that intraluminal MCT is suitable as a fat energy source during intestinal inflammation in rats. We suggest that Twinline may be more useful to improve nutritional status and to re-duce the mucosal inflammation in rat colitis, but that Twinline is equal in effect to Elental for rat enteritis.

A comparison of the effects of medium- and long-chain triglycerides on neutrophil stimulation in experimental ileitis

Background: In ileitis, the chain length of dietary fats affects inflammation, and medium-chain triglycerides (MCTs), but not long-chain triglycerides (LCTs), reduce intestinal damage. The mechanism of this effect has not been fully elucidated. In this work, we studied the effects of MCTs and LCTs on polymorphonuclear neutrophil (PMN) action in trinitrobenzene sulfonic acid (TNB)-induced ileitis. Methods: Twelve-week-old male Sprague-Dawley (SD) rats received TNB in the ileal lumen and were then fed MCTs or LCTs for 3 days. Results: We detected no significant differences in the morphological damage between the MCT and the LCT groups. The content of interleukin (IL)-8, on the other hand, was significantly lower in the MCT group than in the LCT group, as was myeloperoxidase activity. The CD11b expression by PMNs was higher in the LCT group, but the difference was not of statistical significance. Conclusions: These findings suggested that proinflammatory activity was greater in the LCT group in comparison with the MCT group.

Changes in lymphocyte phenotypes and cytokine production by surgical stress in a rat small intestinal resection model.

Small intestinal resection rats are used widely as a malabsorption model, but the immunological changes are unclear. We examined the changes in systemic and mucosal immune status after a small intestinal resection in rats with a controlled nutritional status. Rats had 60% of their small intestine removed. At 5 days after the surgery, spleen cells and intraepithelial lymphocytes (IEL) were isolated. The phenotypes of spleen cells and IEL, the production patterns of Th1 and Th2 cytokines, and the proinflammatory cytokine levels in the plasma were measured. CD4+ T cells in the blood and spleen were significantly decreased in the Resection group (p<0.05). In contrast, IEL subpopulations were not different between the two groups. Interferon-γ production from the spleen cells was significantly decreased in the Resection group (p<0.05). Interleukin (IL)-4 production was not different between the two groups. Plasma IL-6 concentrations were significantly elevated in the Resection group 6 h after surgery (p<0.05). In conclusions, small intestinal resection in rats suppressed systemic immunity, and this model is useful as a surgical stress model.

Different-sized triglycerides chains do not influence colitis induced by trinitrobenzene sulfonic acid in rats

Abstract An elemental diet (ED) was established as a primary therapy for patients with Crohn’s disease, and one of its therapeutic mechanism might be due to its low fat content. However, it is thought to be important to investigate not only the quantity of dietary fat, but also the quality of the dietary fat. We therefore studied the effects of medium chain triglycerides (MCT) versus long chain triglycerides (LCT) on colitis induced by trinitrobenzene sulfonic acid (TNBS) in rats in order to investigate whether enteral nutrition containing different-sized triglycerides chain influence intestinal inflammation. An elemental diet containing MCT or LCT was administered for 7 days through an intragastric catheter after an intracolonic injection of TNBS. The mucosal damage series in both groups did not differ significantly. The myeloperoxidase activities, leukotriene B4 levels and interleukin-8 levels also did not change between the MCT and LCT groups. These results indicated that 7 days of administration of different-sized triglycerides did not influence the rat colitis induced by TNBS.

Effects of Caloric Intake on Intestinal Mucosal Morphology and Immune Cells in Rats Treated with 5-Fluorouracil

Anticancer drugs have been reported to damage the intestinal mucosa. We evaluated the effects of caloric intake on the mucosal morphology and immune cells in rats treated with 5-fluorouracil (5-FU). Rats were received a liquid diet plus 5-FU treatment for 8 days as follows: Low calorie group (25 kcal/day with 5-FU), Normal calorie group (50 kcal/day with 5-FU), and Control group (50 kcal/day with saline). The mucosal morphology, cell numbers and phenotypes of spleen and intraepithelial lymphocytes (IEL) were assessed. As compared with the control group, the villus heights were significantly lower in the Low calorie group, but not significantly lower in the Normal calorie group. The total cell yield from the spleen, CD4+ and CD8+ T cells decreased in the Low and Normal calorie group, but these changes were less pronounced in Normal calorie group. The total cell yield from the IEL also decreased in the Low calorie group, but not in the Normal calorie group. Our study demonstrated that sufficient caloric intake attenuated the damages in intestinal morphology and in the immune cell numbers. Clinically, nutritional support would be expected to be one approach to reducing the risk of bacterial translocation or infection induced by chemotherapy.