Fat-free Total Parenteral Nutrition Research Articles

Soybean fat supplementation controls insulin resistance caused by fat-free total parenteral nutrition

Conscious young adult male rats were given total parenteral nutrition (TPN) with or without soybean fat for 4 days. Those given fat-free TPN developed severe fatty liver, with hyperglycaemia, hyperinsulinaemia, and hypotriglyceridaemia. These disorders were clearly improved by supplementing TPN with soybean fat, in an amount equivalent to 20% of total calories, and correspondingly reducing glucose. Insulin resistance also developed over a 4-day infusion of fat-free TPN in mature rats. Even after over-night fasting after stopping the TPN infusion, the levels of serum glucose and insulin were higher in the fat-free TPN group than in the control group, and intravenous glucose tolerance test results indicated insulin resistance in the fat-free TPN group. The HOMA-IR index of insulin resistance was significantly improved by supplementation with soybean fat. In conclusion, fat-free TPN infusion induced hyperglycaemia and hyperinsulinaemia, leading to fatty liver and insulin resistance. TPN with glucose should be supplemented with soybean fat emulsion as replacement for part of the glucose calories.

Effects of glucose or fat calories in total parenteral nutrition on fat metabolism and systemic inflammation in rats

This study compared the effects of total parenteral nutrition (TPN) by central vein with or without fat provided at maintenance energy requirement on fatty acid metabolism, de novo lipogenesis, and the risk of hepatic and systemic inflammation in rats. Study 1 was conducted in 2 groups: high glucose (HG), where fat-free TPN was given at maintenance levels of 180 kcal/(kg d), and low glucose (LG), where fat-free TPN containing 30% fewer calories at 126 kcal/(kg d) was provided by reducing 54 kcal/(kg d) from parenteral glucose. Study 2 contained 3 TPN groups: 1 LG group at 126 kcal/(kg d) and 2 groups at 180 kcal/(kg d) with 30% of total calories (54 kcal/[kg d]) either from soybean or fish oil emulsion. In both studies, animals fed a chow diet ad libitum were included. Plasma and hepatic triglyceride and phospholipid fatty acid profiles, enzymes indicating hepatic injury, and C-reactive protein levels (CRP) reflecting systemic injury were measured. In study 1, evidence of de novo lipogenesis was noted in LG and was more prominent in HG with elevation of CRP in HG. In study 2, de novo lipogenesis was reduced by adding either fat to LG to achieve maintenance energy levels. Moreover, adding fat as soybean oil but not fish oil significantly increased plasma and hepatic triglyceride and also elevated aspartate aminotransferase and CRP levels, reflecting inflammation. Thus, in rats, either hypocaloric feeding as glucose-based TPN or TPN provided at maintenance energy levels with the addition of fish oil limits hepatic lipid accumulation and prevents the evidence of hepatic and systemic injury found with maintenance level TPN as glucose only or glucose plus soybean oil.

Supplementation of Fat Emulsion Improves Fatty Liver due to Total-Parenteral Nutrition in Young Adult Rats

Conscious young adult male rats were given total-parenteral nutrition (TPN) with or without a soybean fat emulsion for 4 days and those that did not receive the emulsion (fat-free TPN group) developed severe fatty liver with hyperglycemia,hyperinsulinemia,and hypotriglyceridemia.These disorders were improved by administering TPN supplemented with soybean fat,equivalent to 20% of total calories,with glucose correspondingly reduced.In the fat-free TPN group,the expression of sterol regulatory element binding protein 1c (SREBP1c),acetyl-CoA carboxylase (ACC),and fatty acid synthase (FAS) mRNAs in the liver were coordinately up-regulated,resulting in an increase in non-essential fatty acids and a decrease in essential fatty acids in the liver,due to the fat supply drying up.In contrast,expression of carnitine-palmitoyltransferase (CPT) 1a mRNA decreased.However,in the group given the fat emulsion in their TPN,the expressions of all of the above types of mRNA remained similar to those in an oral diet control group.It appeared that the hyperinsulinemia following infusion of excess glucose had induced lipogenesis and a decrease in fatty acid β-oxidation in the liver and that these changes were prevented by supplementation of soybean fat equivalent to 20% of total calories (with a corresponding reduction in glucose).Therefore,it may be appropriate to routinely supplement fat-free TPN with soybean fat in the clinical situation,substituting it for part of the glucose.In addition,serum glucose and insulin levels should be monitored during TPN infusions.

Soybean Oil Fat Emulsion to Prevent TPN-Induced Liver Damage: Possible Molecular Mechanisms and Clinical Implications

Long-term total parenteral nutrition (TPN) is known to be associated with cholestasis and hepatic steatosis, which can be lethal in infants who cannot be fed orally. The present review focuses on the metabolic complications in the liver that may occur due to the excessive administration of fat-free TPN. We have recently developed an infant rat model of hepatic dysfunction and steatosis induced by overdose of fat-free TPN. In this model, plasma levels of liver enzymes in the fat-free TPN group were found to be significantly higher than in the other groups (i.e., the oral diet and fat-containing TPN groups). Pathological examination showed hepatomegaly and severe fatty changes without cholestasis in the liver of infant rats that received fat-free TPN. We clearly demonstrated that the addition of soybean oil emulsion to the TPN regimen prevented hepatic dysfunction and fatty changes. In the present review, we discuss the molecular mechanism of the hepatic dysfunction induced by fat-free TPN and the role of soybean oil fat emulsion in the TPN regimen. We also discuss the clinical implications of soybean oil-containing TPN solutions and point out the importance of including fat in the TPN regimen in order to prevent the hepatic abnormalities associated with the excessive administration of fat-free TPN.

Role of Soybean Oil Pat Emulsion in the Prevention of Hepatic Xenobiotic Transporter mRNA Up- and Down-Regulation Induced by Overdose of Pat-free Total Parenteral Nutrition in Infant Rats

Total parenteral nutrition (TPN) is associated with cholestasis and hepatic steatosis in human infants. The present study focused on the changes in hepatic xenobiotic transporters associated with overdose of fat-free or fat-containing TPN in infant rats. Three-week-old male Sprague-Dawley rats were divided into three groups: group 1 received an oral diet, group 2 received TPN without fat, and group 3 received TPN with 20% of its calories from fat (soybean oil emulsion). After TPN administration for 4 days, both serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, which are indicators of hepatic dysfunction, in group 2 were significantly higher (p<0.001) than those in the other groups, whereas there were no differences between groups 1 and 3 in either serum AST or ALT levels. The serum bilirubin concentration in group 2 was also markedly higher than that in the other groups. Mdr2, Bsep, Mrp2, Mrp6, Oct1, and Oat2 mRNA levels were decreased in group 2 (fat-free TPN) compared with those in group 1 (oral diet), whereas Mdr1b, Mrp1, and Mrp5 mRNA levels were increased. Specifically, the level of Mdr1b mRNA in group 2 was 16 times higher (p<0.001) than that in group 1. On the other hand, the changes in these mRNA expression levels in group 3 (fat-containing TPN) were smaller than those in group 2, and specifically, the expression levels of Mdr1b, Mrp1, Mrp5, Mrp6, and Oat2 mRNA in group 3 were not significantly different from those in group 1. The results of the present study indicate that including fat in the TPN regimen is very important in preventing the mRNA up- and down-regulation of xenobiotic transporters, which is considered to be the main factor responsible for the abnormal hepatic changes such as cholestasis associated with the excessive administration of fat-free TPN.

Major Role of Soybean Oil in Preventing Decrease in CYP4A1 mRNA Content Relative to PPAR.ALPHA. mRNA Down-Regulation in Infant Rats

Changes in the levels of CYP4A1, PPARalpha, and RXRalpha mRNA expression in the liver following overdose of fat-free or fat-containing total parenteral nutrition (TPN) were studied in 3-week-old male Sprague-Dawley rats. The rats were divided into three groups: group 1, oral diet; group 2, fat-free TPN; and group 3, TPN with 20% of calories from soybean oil emulsion. Levels of CYP4A1, PPARalpha, and RXRalpha mRNA in the fat-free TPN group were significantly lower than those in the other groups. Levels of CYP4A1 and PPARalpha mRNA were strongly correlated (r=0.849), and levels of CYP4A1 and RXRalpha mRNA were weakly correlated (r=0.618). This is the first report of a strong correlation between the levels of CYP4A1 and PPARalpha mRNA following overdose of fat-free or fat-containing TPN in infant rats. Our results also indicate that it is important to include fat in TPN regimens in order to prevent CYP4A1 mRNA down-regulation, which may be related to changes in PPARalpha mRNA levels in the liver.

Significance of administration of fat emulsion: hepatic changes in infant rats receiving total parenteral nutrition with and without fat

Total parenteral nutrition (TPN) is associated with cholestasis and hepatic steatosis, which can be lethal in infants who cannot be fed orally. The present animal study focused on the metabolic complications in the liver that may occur due to the excessive administration of fat-free TPN. Thirty infant (3-week-old) male SD rats weighing 60−70 g were randomly allocated to five groups ( n=6): the OD group received an oral diet, the FT group received an oral diet and was fasted overnight on the last day of experiment before sacrifice, the 0% fat group received TPN without fat, the 20% fat group received TPN with 20% of calories from fat emulsion, and the 40% fat group received TPN with 40% of calories from fat emulsion. All TPN regimens were isocaloric, isonitrogenic, and administered for 4 days. In the 0% fat group, plasma levels of liver enzymes were significantly higher than in the other groups. Pathological examination showed hepatomegaly and severe fatty changes without cholestasis in the 0% fat group. The results of this study in infant rats indicate the importance of including fat in the TPN regimen in order to prevent the abnormal hepatic changes associated with the excessive administration of fat-free TPN.

Abnormal regulation of serum lipid fatty acid profiles in short gut rats fed parenteral nutrition with lipid

Despite absence of essential fatty acid deficiency (EFAD), increases in arachidonic acid to linoleic acid ratios occur in serum phospholipid of patients treated with chronic total parenteral nutrition (TPN). The parenteral lipid component of TPN contains abundant linoleate; thus low phospholipid linoleate may reflect increased conversion to arachidonate. Arachidonic acid excess has been associated with a proinflammatory milieu through increased eicosanoid production and might contribute to the increases in inflammatory markers seen in home TPN patients. We investigated fatty acid metabolism in a rodent model of malabsorption. We hypothesized that short gut rats would metabolize parenteral lipid differently from intact rats. We performed laparotomy and 80% small bowel resection (or sham surgery) in rats. Sixteen sham and 16 short gut rats were randomly assigned to TPN with lipid or fat-free TPN. After 5 days, weight loss was similar in all groups. Analysis of serum phospholipids demonstrated that 20:3ω9 (eicosatrienoic acid) was relatively increased in fat-free TPN groups, irrespective of surgery type, as were distal very long chain ω3 class fatty acids, as anticipated. Uniquely, both nutrition (TPN/lipid v fat-free TPN) and surgery type (sham v short gut) were significant in determining arachidonic acid levels. Relatively elevated arachidonate occurred in both groups of fat-free rats, suggesting increased Δ6 and/or Δ5 desaturase activity, as expected. In contrast, giving TPN/lipid lowered arachidonate (suggesting appropriately downregulated desaturases) in sham animals, but not in short gut animals. Ratios of arachidonic and di-homo-γ-linolenic to linoleic acids further suggested increased turnover of precursor ω6 to arachidonic acid in short gut rats given lipid compared with the other groups. These preliminary data show that intravenous (IV) lipid gave rise to serum lipid fatty acid profiles that differed in short gut and sham rats. The short gut rat may have a heightened hepatic desaturase activity, inappropriate for the quantity of linoleic acid provided parenterally. Therefore, the short gut rat is an appropriate model to study further arachidonic acid excess in home TPN patients.

Intestinal Adaptation Occurs Independently of Parenteral Long-Chain Triacylglycerol and with No Change in Intestinal Eicosanoids after Mid-Small Bowel Resection in Rats

The role of enteral or parenteral long-chain triacylglycerol (LCT) in the complex process of intestinal adaptation is poorly defined and may involve alterations in eicosanoid synthesis. Our objective was to determine whether provision of parenteral LCT stimulates eicosanoid synthesis and resection-induced intestinal adaptation. We assessed small bowel structural adaptation, the fatty acid profiles of liver, plasma and jejunal mucosa, and the profile of 11 eicosanoids derived from (n-6) PUFA of the jejunal mucosa in rats maintained with total parenteral nutrition (TPN) with 0 or 32% of nonprotein energy from Intralipid for 7 d after mid-small bowel resection or transection control surgery. There was no evidence of biochemical essential fatty acid (EFA) deficiency in the absence of parenteral fat. Resection-induced gut growth occurred independently of parenteral LCT based on significant mucosal hyperplasia in the jejunum and ileum. The mucosal profile of linoleic acid in the total lipid extract of jejunum increased with the presence of parenteral LCT, but decreased with resection without differences in arachidonic acid. There were no differences in the jejunal profile of 11 (n-6)-derived eicosanoids among the four TPN groups as determined by tandem MS. In summary, small bowel resection-induced adaptation occurs independently of parenteral LCT, and fat-free TPN without EFA deficiency does not alter the profile of jejunal (n-6)-derived eicosanoids. Thus, parenteral administration of LCT does not appear to alter jejunal eicosanoid synthesis nor is it beneficial in stimulating intestinal adaptation.

Influences of soybean oil emulsion on stress response and cell-mediated immune function in moderately or severely stressed patients

OBJECTIVES: We previously reported that ω-6 fat emulsion increases cytokine production in burned rats. Effects of soybean oil emulsion on surgical stress responses and lymphocyte function according to the surgical severity have not been studied in detail. We investigated the effects of soybean oil emulsion, which contains 50% ω-6 fatty acid, on postoperative stress responses and cell-mediated immune function according to the severity of surgical stress. METHODS: Eight patients who underwent gastric or colorectal surgery and nine who underwent esophagectomy were fed fat-free total parenteral nutrition. Ten patients who underwent gastric or colorectal surgery and seven who underwent esophagectomy were fed total parenteral nutrition with soybean oil emulsion. Total parenteral nutrition provided 1.5 g of protein and 40 kcal per kilogram every day from 7 d before surgery to postoperative day 14. Soybean oil emulsion (Intralipid) accounted for 20% of the total calories. Serum interleukin-6, C-reactive protein, glucagon, and concanavalin A-N or phytohemagglutinin-stimulated lymphocyte proliferation were determined. RESULTS: In the group of moderately stressed patients, soybean oil emulsion did not amplify the measured levels. In the group of severely stressed patients, soybean oil emulsion amplified the level of serum interleukin-6 and decreased concanavalin A- or phytohemagglutinin-stimulated lymphocyte proliferation. CONCLUSIONS: Soybean oil emulsion amplifies the stress responses and possibly suppresses cell-mediated immune function induced by surgical stress in severely stressed patients, but not in moderately stressed patients.

A summary of our work: effects of intravenous ω-6 and ω-3 fat emulsions on nitrogen retention and protein kinetics in burned rats

The effect of w-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.

Increased urinary peroxides in newborn infants receiving parenteral nutrition exposed to light

To determine whether peroxide loads infused with total parenteral nutrition (TPN) are fully quenched by premature infants. After baseline urine peroxide levels were established, the effect of various parenteral regimens was correlated with urinary peroxide levels in 64 newborn infants </=32 weeks' gestation. This correlation was achieved with the properties of light and of various parenteral nutrient admixtures on the generation of peroxides. Peroxides were measured by the ferrous oxidation of xylenol orange. The level of urinary peroxides measured for infants given a fat-free TPN regimen unprotected from light (74.5 +/- 15.3 micromol/L) was similar to levels found in infants given a lipid-containing regimen (88.1 +/- 10.3 micromol/L). When photoprotected, the fat-free alimentation was associated with peroxide levels (28.8 +/- 2.8 micromol/L) similar to those measured before TPN (27.6 +/- 4.1 micromol/L). Because urine peroxide levels are changed by various nutritional procedures, antioxidant systems of premature infants are unable to fully quench the oxidant load associated with TPN.

Contribution of multivitamins, air, and light in the generation of peroxides in adult and neonatal parenteral nutrition solutions.

To compare the concentrations of peroxides between adult and neonatal total parenteral nutrition (TPN) solutions in response to protection against inducers of peroxidation such as multivitamins and exposure to light or air. Peroxide concentrations were measured in freshly prepared adult and neonatal solutions of fat-free TPN in four settings: with or without an air inlet, and protected or unprotected from ambient light. An oxygen washout was performed by exposing a fat-free neonatal TPN solution to a continuous flow of nitrogen. Globally, light was the main inducer of peroxides in adult and neonatal solutions. However, in adult solutions the concentration of peroxides remained <15 micromol/L, while in neonatal solutions the peroxide concentration was as high as 300 micromol/L in ambient light. Although the oxygen washout did prevent the generation of peroxides, avoiding air inlet was not as effective as was photoprotection in decreasing the important peroxide load in the neonatal TPN solution. The higher concentration of peroxides found in neonatal solutions compared with adult solutions is explained by the differences in nutrient composition between the two solutions. Contamination of parenteral solutions by air during compounding accounts for the photoinduced generation of peroxides in TPN solutions. It is more convenient to protect TPN solutions from light exposure after the admixture of the multivitamin solution than to avoid contact with oxygen.

Protecting solutions of parenteral nutrition from peroxidation.

Light exposure induces the generation of peroxides in solutions of total parenteral nutrition (TPN). Peroxide toxicity has been documented in cell, in tissue, and in isolated organs. To decrease the infused peroxide load and to protect the quality of the parenteral nutrients, we tested the photoprotective properties of different infusion sets. Solutions of fat-free TPN and all-in-one total nutrient admixture (TNA) were run through sets of bags (clear and covered) and tubings (clear and colored: black, orange, and yellow) offering different levels of protection against light. Peroxide levels were determined by ferrous oxidation of xylenol orange, thiol functions by the 5,5,-dithiobis(2-nitrobenzoic acid) technique, and absorbance of tubings by spectroscopy. Protection of only the bag had little effect on peroxide generation. In fat-free TPN solutions kept in covered bags, peroxide concentrations were 1.5 to 2 times higher when run through clear compared with colored tubings. When exposed to phototherapy or in the presence of lipids, peroxides were two to three times higher with the clear compared with the black tubing; meanwhile, orange and yellow tubings offered varying levels of protection related to their light-absorbing properties. Colored tubings offered a greater protection against the disappearance of thiol functions. Covering bags and using orange and yellow tubings may be a practical solution to reduce infused peroxide loads from about 400 to 100 microM. This is especially relevant in patients with an immature or a compromised antioxidant capacity or when phototherapy or preparations of TNA are used.

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

The effect of omega-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 omega 6 received safflower oil fat emulsion, which accounted for 20% of total caloric intake (n = 11). Group omega 3 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 omega-6 essential fatty acids. Cumulative nitrogen balance was decreased significantly in group omega 6. The rates of whole-body protein synthesis were increased significantly in both groups omega 6 and omega 3. In omega 6, 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 E2 and thromboxane B2 concentrations were not significantly different among three groups. Supplementation with the new omega-3 fat emulsion, however, improved protein metabolism in burned rats receiving TPN.

Effects of soybean oil emulsion and eicosapentaenoic acid on stress response and immune function after a severely stressful operation.

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. 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. 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. 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. Soybean oil emulsion amplifies, and the supplementation of EPA reduces, the stress response and stress-induced immunosuppression.

Effects of intravenous omega-3 and omega-6 fat emulsion on cytokine production and delayed type hypersensitivity in burned rats receiving total parenteral nutrition.

The effects of fat emulsions containing omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) on fatty acid profile, cytokine production, and delayed type hypersensitivity (DTH) in burned rats receiving total parenteral nutrition (TPN) were investigated. A fat emulsion containing only eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was prepared (omega-3 fat emulsion). Sprague-Dawley rats were fed fat-free chow for 2 weeks and were divided into three groups according to the contents of TPN. Groups C (n = 11) and C' (n = 14) received fat-free TPN. Group omega6 received safflower oil emulsion containing linoleic acid (omega-6 PUFA) (n = 11). Group omega3 (n = 11) received safflower oil emulsion (19% of total caloric intake) and fat emulsion containing only EPA and DHA (1% of total calories). On day 5, all rats except for those in group C' were subjected to a 20% full-thickness burn. Group C' did not receive burns. After 48 hours, the rats were killed. The interleukin (IL)-8 concentration was significantly 45% lower in group omega3 than in group C (p < .05). The IL-10 concentration was significantly 15% lower in group omega3 than in group omega6 (p < .05). The IL-6 concentration was increased in group omega6 but not in group omega3 when compared with group C. The IL-6 and IL-8 were not detected in group C'. Prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) concentrations were increased by burn injury, but there were no significant differences among the burned groups. Cell-mediated immunity was thus significantly decreased in burned groups (groups C, omega6, and omega3; p < .01). However, the decrease of DTH was smaller in group omega3 and significantly greater when compared with groups C and omega6 (p < .05). omega-6 PUFAs increased serum inflammatory cytokine levels in a stressed state. omega-3 fat emulsion reduced IL-8 and IL-10 levels and prevented immunosuppression in burned rats that were receiving TPN.

Total parenteral nutrition supplemented with medium-chain triacylglycerols prevents atrophy of the intestinal mucosa in septic rats.

Total parenteral nutrition (TPN) is associated with an increased incidence of bacterial translocation (BT) compared with enteral nutrition because of the disuse atrophy of the intestine. In this study, we assessed the effect of adding medium-chain triacylglycerols (MCT) to TPN for the prevention of mucosal atrophy in the intestine. Rats were subjected to either fat-free TPN, TPN with long-chain triacylglycerols (LCT), or TPN with MCT for 5 d and nutrition parameters were evaluated. In another set of rats receiving the same TPN regimen, 0.8 or 0.05 mg/kg endotoxin was administered on day 4. Survival was evaluated and BT to the mesenteric lymph nodes, liver, and systemic blood was measured 24 h later. The mucosal heights of the jejunum and ileum were evaluated concurrently. The survival rate was significantly improved in the MCT group (P < 0.05) at the endotoxin dose of 0.8 mg/kg. The nutrition condition presented by phospholipid, total cholesterol, and total ketone body levels was the best in the MCT group compared to the other groups. The intestinal villous height in the ileum was significantly greater in the MCT group. However, the improvement of BT in MCT group was not statistically significant. In this endotoxin-challenged rat model, survival rate was improved by the supplementation of MCT. This effect may be presented in some part by the improvement in nutrition condition and by the prevention of mucosal atrophy in the intestine.

Admixture of a Multivitamin Preparation to Parenteral Nutrition: The Major Contributor to In Vitro Generation of Peroxides

Peroxides have been reported to contaminate lipid emulsions and amino acid solutions used in total parenteral nutrition (TPN). This is particularly disturbing in newborn infants who are prone to several diseases related to immature defense mechanisms against oxidative challenges. It is not clear whether the antioxidants in multivitamins help protect parenteral nutrients against the hazards of oxidation. To evaluate the role of a multivitamin preparation (MVI) on the actual peroxide load received by patients on TPN. The generation of peroxides in parenteral nutrition was tested first using test solutions. We compared the relative contribution of commercially available amino acid solutions, a lipid emulsion, and MVI on the level of peroxides in clinically relevant TPN solutions. Second, we measured the level of peroxides actually infused at the bedside. In both circumstances, the effects of time and light exposure were isolated. The level of peroxides was determined by a colorimetric technique and expressed as microM equivalents tert-butyl hydroperoxide (microM = TBH). Even when protected from light, the addition of MVI produced a 10-fold increase in peroxides (mean +/- SEM, n = 3, 19 +/- 4 to 189 +/- 8 microM = TBH at 4 h) in the fat-free TPN solution and a fourfold increase (64 +/- 6 to 244 +/- 8 microM = TBH at 4 h) in the lipid-containing TPN solution. A dose-response relationship was found between the concentration of MVI and peroxide levels. The effect of light was the strongest in the presence of multivitamins. The amino acid solutions had a relative inhibitory effect on the generation of peroxides by MVI, which varied (from 54 +/- 1% to 72 +/- 1%) all according to the amino acid blend. In parenterally fed premature infants, protecting the intravenous set from light decreased the load of infused peroxides (146 +/- 15 vs 215 +/- 24 microM = TBH). The lipid emulsion had a significant but minor additive effect compared with the multivitamin preparation, which was the major contributor to the generation of peroxides. Protection from photooxidation is not sufficient to prevent peroxidation of TPN solutions. Contrary to what one would expect, increasing the concentration of MVI will lead to a greater generation of peroxides, suggesting that the essential antioxidants in MVI do not have antiperoxide properties.

Study on optimal fat content in total parenteral nutrition in partially hepatectomized rats.

In order to investigate the optimal fat content for total parenteral nutrition (TPN) solutions, male Wistar rats were subjected to 70% hepatectomy and then placed, for five days, on one of five TPN regimens in which fat represented 0%, 10%, 20%, 30% and 40%, respectively, of the total calorie content. As serum triglyceride levels in the fat-treated groups were lower than those in the non-treated normal rats, it was concluded that the administered fat was sufficiently hydrolyzed. The greater the fat content, the higher the regeneration rate of the remnant liver. Significant differences were found between the 0%-fat group and 20%-plus fat groups. Hepatic triglyceride level was significantly lower in the 20%-fat group. Hepatic protein level was significantly elevated in all fat-treated groups. Serum phospholipids and total cholesterol due to the lecithin contained in fat emulsion were significantly elevated in the 30 and 40%-fat groups, indicating that fat content of 30 and 40% was excessive. The results suggest that TPN containing fat is superior to fat-free TPN for liver regeneration after partial hepatectomy, and that optimal fat content is estimated to be about 20% of total calorie content in the case of this fat emulsion.