Toshiyuki Sugiura

Effects of Soybean Oil Emulsion and Eicosapentaenoic Acid on Stress Response and Immune Function After a Severely Stressful Operation

OBJECTIVE To investigate the effects of soybean oil emulsion and oral or enteral administration of eicosapentaenoic acid (EPA) on stress response, cytokine production, protein metabolism, and immune function after surgery for esophageal cancer. SUMMARY BACKGROUND DATA It has been reported that safflower oil, rich in n-6 polyunsaturated fatty acid (n-6 PUFA), affects the survival rate of septic animals and decreases the immune function. It has also been reported that the administration of fish oil, in contrast, reduces these stress responses and stress-induced immunosuppression. In humans, the effects of soybean oil emulsion and the administration of EPA on stress response and immune function after surgery have not been established. METHODS Patients who underwent esophagectomy with thoracotomy were divided into three groups. Seven patients were fed by total parenteral nutrition (TPN) with soybean oil emulsion, which accounted for 20% of total calories. Seven patients were given oral or enteral administration of 1.8 g/day EPA, in addition to TPN with soybean oil emulsion. Nine patients served as the control group; these patients received fat-free TPN. Serum interleukin-6 (IL-6), C-reactive protein, concanavalin A (con A)- or phytohemagglutinin (PHA)-stimulated lymphocyte proliferation, natural killer cell activity, and stress hormones were measured. RESULTS The postoperative level of serum IL-6 was significantly higher in the group receiving soybean oil emulsion than in the fat-free group. Oral or enteral supplementation of EPA with soybean oil emulsion significantly reduced the level of serum IL-6 compared with the patients receiving soybean oil emulsion. Con A- or PHA-stimulated lymphocyte proliferation decreased significantly on postoperative day 7 in all groups of patients. The supplementation of EPA with soybean oil emulsion significantly improved the lymphocyte proliferation and natural killer cell activity on postoperative day 21 compared with the group receiving soybean oil emulsion. CONCLUSIONS Soybean oil emulsion amplifies, and the supplementation of EPA reduces, the stress response and stress-induced immunosuppression.

Effect of intravenous ω-6 and ω-3 fat emulsions on nitrogen retention and protein kinetics in burned rats

Abstract The effect of ω-3 fat emulsion on nitrogen retention and kinetics in relation to fatty acid profile were investigated in burned rats receiving total parenteral nutrition (TPN). A fat emulsion of a structured symmetrical triacylglycerol containing only eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (2:1) was prepared. Sprague-Dawley rats were fed by fat-free chow for 2 wk. Then rats were fed exclusively with one of three types of TPN for 7 d. Animals in group C received fat-free TPN ( n = 11). Group ω6 received safflower oil fat emulsion, which accounted for 20% of total caloric intake ( n = 11). Group ω3 received fat emulsion containing only EPA and DHA (1% of total calories, n = 11), in addition to safflower oil emulsion (19% of total calories). On day 5, each rat was subjected to 20% full-thickness scald burns. Rats were sacrificed under ether anesthesia 48 h after burning. The rats in group C became deficient in ω-6 essential fatty acids. Cumulative nitrogen balance was decreased significantly in group ω6. The rates of whole-body protein synthesis were increased significantly in both groups ω6 and ω3. In ω6, however, the rates of whole-body protein breakdown were increased significantly. In conclusion, the rates of whole-body protein breakdown increased and nitrogen retention was aggravated significantly in animals administered the safflower oil emulsion. Significant increases of urinary excretion of total catecholamine were also observed. Prostaglandin E 2 and thromboxane B 2 concentrations were not significantly different among three groups. Supplementation with the new ω-3 fat emulsion, however, improved protein metabolism in burned rats receiving TPN.

Effects of total parenteral nutrition on endotoxin translocation and extent of the stress response in burned rats

Postburn endotoxin translocation has been well documented. However, the relationship between the secretion of catabolic hormones, degree of endotoxin translocation, and intestinal atrophy has not been previously demonstrated. In this experiment, modulation of the secretion of catabolic hormones according to the route of nutrient administration was examined in burned animals. A total of 55 rats, with and without a burn injury, were orally or parenterally fed. Urinary excretion of epinephrine and norepinephrine (U-EN) of each rat was measured for 48 h after burn injury as an indicator of the stress response. Evaluations of intestinal atrophy and endotoxin contents in the liver and spleen were also done 48 h after burn injury. U-EN after burn injury in rats administered total parenteral nutrition (TPN) was higher than in those fed orally. Endotoxin translocation and intestinal atrophy after thermal injury were also augmented by TPN. A significant positive correlation between U-EN and endotoxin content of the liver, and a negative correlation between U-EN and weight of the intestine, were observed. TPN enhances the stress response after burn injury. An increase in endotoxin translocation and intestinal atrophy by TPN are closely related to enhancement of the stress response.

Effects of a Newly Developed Fat Emulsion Containing Eicosapentaenoic Acid and Docosahexaenoic Acid on Fatty Acid Profiles in Rats

A new fat emulsion of symmetrical triacylglycerols, containing only eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was developed. The effects of this preparation on serum and liver fatty acid composition were investigated. Male Sprague-Dawley rats were fed a fat-free oral diet for 2 wk and were then divided into two groups. Seven rats were infused for 7 d with 1 mL of the new fat emulsion, which accounted for 1% of total caloric intake. The other 7 rats received saline. Both groups of rats received a fat-free diet during the infusion. EPA and DHA decreased to one third to one fifth of normal value after 2 wk on a fat-free diet. EPA and DHA of serum and liver remained at a low level in the control group throughout the study. But in the rats administered with the new fat emulsion, EPA and DHA increased rapidly and exceeded normal values in both serum and liver after 7 d of infusion. Decreased arachidonic acid with increased 20:3n-9 resulted in the rise of the triene/tetraene (T/T) ratio to greater than 0.4, indicating an n-6 essential fatty acid deficiency in the control rats. In the group administered the new fat emulsion, however, 20:3n-9 and total content of monounsaturated fatty acids decreased significantly, and the T/T ratio was less than than 0.4 in both serum and liver. In conclusion, the intravenous use of a newly developed fat emulsion containing EPA and DHA is useful in improving the EPA and DHA status of serum and liver without any harmful effects. Beneficial effects are expected in the modulation of inflammatory and stress response.

Effects of insulin-like growth factor-1 on endotoxin translocation in burned rats receiving total parenteral nutrition.

The purpose of this study was to investigate the effect of insulin-like growth factor-1 (IGF-1) on the translocation of endotoxin from the gut of burned rats. Twenty-eight male Sprague-Dawley rats (7-wk-old) were subjected to 20% full-thickness scald burns and were divided into two groups. One group received 4 mg.kg-1.d-1 of IGF-1 (IGF-1 group, n = 14), and the other received saline (control group, n = 13). All rats were fed exclusively by total parenteral nutrition (TPN). On the second postburn day, rats were killed. The amount of endotoxin in the liver and spleen were measured. RNA from the terminal ileum was extracted, and Northern blot analyses of alpha-tubulin, beta-actin, cell division cycle-2 (cdc2), and immunoglobulin-A (IgA) were performed. Nitrogen balance was improved (p < 0.001), and the wet weight of intestine and its mucosa were increased significantly in the burned rats that received IGF-1. Gene expression of alpha-tubulin and beta-actin were not changed. Cdc2 was elevated (P < 0.05), but IgA was decreased (P < 0.05) in the IGF-1 group. Levels of endotoxin in the liver and spleen were significantly reduced (P<0.05) by the administration of IGF-1. A negative correlation between the levels of endotoxin in the liver and the weight of the intestinal mucosa was observed. In conclusion, IGF-1 improved nitrogen balance, promoted the proliferation of intestinal mucosa and reduced the translocation of endotoxin.

Effect of IGF-1 on Protein Metabolism in Burned Rats

The effects of insulin-like growth factor-1 (IGF-1) on the catabolic and immune response induced by thermal injury were studied in burned rats fed by TPN. An increase of synthesis greater than the increase of breakdown resulted in improved nitrogen retention in the IGF-1 group. There was no effect on the mRNA in the structural proteins of the skeletal muscle and liver. However, the gene expression of albumin and the structural proteins of the diaphragm increased significantly in the rats receiving IGF-1. The proliferation of the gut mucosa and the fractional protein synthesis rate of the small intestine increased, and the endotoxin content of the liver and spleen were smaller in the burned rats that received IGF-1. Delayed type hypersensitivity increased significantly (p < .01) in the IGF-1 group. In conclusion, IGF-1 improved the whole-body protein metabolism, and albumin and respiratory muscle protein synthesis in the burned rats. It significantly promoted the proliferation of the intestinal mucosa, and reduced the intestinal translocation of endotoxin. Cellular immunity was also enhanced.