Karina V. Barros

Soybean and fish oil mixture increases IL-10, protects against DNA damage and decreases colonic inflammation in rats with dextran sulfate sodium (DSS) colitis

It was investigated whether dietary polyunsaturated fatty acids (PUFA) could influence colonic injury, tissue DNA damage, cytokines and myeloperoxidase activity (MPO) and plasma corticosterone in DSS-induced colitis rats. Male weaning Wistar rats were fed for 47 days with an AIN-93 diet with control (C), fish (F) or a mixture of fish and soybean oil (SF). The colitis was induced from day 36 until day 42 by 3% DSS in drinking water. On day 48, blood samples were collected for corticosterone determination. The distal colon was excised for histological analysis and to quantify the cytokine (IL-4, IL-10 and INF-γ), MPO and DNA damage. The disease activity index (DAI) was recorded daily during colitis induction. The DAI, MPO, histological analyses showed decreases only in the SF group compared with the C group. IL-10 was increased and DNA damage was reduced in the groups F and SF, and an inverse correlation between these variables was found. There were no differences in corticosterone, IFN-γ and IL-4 levels. Soybean and fish oil mixture may be effective in improving colonic injury and DNA damage, and it could be an important complementary therapy in UC to reduce the use of anti-inflammatory drugs and prevent colorectal cancer.

Pharmaconutrition: acute fatty acid modulation of circulating cytokines in elderly patients in the ICU

BACKGROUND Enteral supply of ω-3 polyunsaturated fatty acids has been used in an attempt to modulate inflammation and improve outcome in critically ill patients. However, enteral administration may be slow to change membrane composition and therefore may not be the best route to supply these fatty acids in patients with acute conditions. This study evaluated the effects of short-term intravenous (IV) administration of fish oil-based lipid emulsion (FLE) as pharmaconutrition on cytokine levels in critically ill elderly patients. METHODS Enterally fed patients (n = 40; aged 60-80 years) were recruited in the first 48 hours of intensive care unit (ICU) admission. Fifteen patients received IV FLE (0.2 g/kg body weight) over 6 hours for 3 consecutive days, and 25 patients did not receive IV lipid (control). Samples were collected before and 24 hours and 72 hours after the third FLE infusion. Nutrient intakes, clinical parameters, and serum cytokine concentrations were measured. RESULTS Compared with the control, FLE resulted in higher energy intake, lower serum tumor necrosis factor-α and interleukin (IL)-8 concentrations, and higher serum IL-10. These differences occurred around 7-9 days of ICU stay at the time of the patients extubation. ICU stay, mortality, and markers of coagulation and liver function did not differ between groups. CONCLUSIONS Short-term IV FLE modulates some inflammatory markers in critically ill elderly patients receiving enteral nutrition (EN), suggesting an anti-inflammatory effect. This may be a benefit and suggests a role for FLE administration as a supplement in elderly ICU patients receiving standard EN.

Effects of a high fat or a balanced omega 3/omega 6 diet on cytokines levels and DNA damage in experimental colitis

OBJECTIVE High-fat diets have been shown to be a risk factor for ulcerative colitis (UC). Omega-6 polyunsaturated fatty acids are considered to increase lipid peroxidation, while the omega-3 polyunsaturated fatty acid exerts a chemopreventative effect. We evaluated the effect of high-fat diets (20%) enriched with fish or soybean oil on colonic inflammation and DNA damage in dextran sulfate sodium-induced colitis. METHODS Male Wistar rats (28-30 days) were fed an American Institute of Nutrition (AIN)-93 diet for 47 days and divided into five groups: control normal fat non-colitic (C) or control colitis (CC), high soybean fat group (HS) colitis, high fish fat group colitis, or high-fat soybean plus fish oil colitis. UC was induced from day 35 until day 41 by 3% dextran sulfate sodium. On day 47, the rats were anesthetized; blood samples collected for corticosterone determination, and the distal colon was excised to quantify interleukin-4 (IL-4), IL-10, and interferon-gamma levels, myeloperoxidase activity, histological analyses, and DNA damage. The disease activity index was recorded daily. RESULTS The disease activity index, histological analysis, myeloperoxidase activity, IL-4, interferon-gamma, and corticosterone levels did not differ among the colitic groups. IL-10 was significantly increased by the high fish fat group diet in relation to HS, but only the high soybean-fish fat diet increased the IL-10/IL-4 ratio (anti-inflammatory/pro-inflammatory) to levels closer to the C group and reduced DNA damage compared to the HS group (P<0.05). CONCLUSION The data show that high-fat diets did not exacerbate UC and suggest that the soybean and fish oil mixture, more than the fish oil alone, could be a complementary therapy to achieve a cytokine balance in UC.

Supplemental intravenous n-3 fatty acids and n-3 fatty acid status and outcome in critically ill elderly patients in the ICU receiving enteral nutrition

BACKGROUND & AIMS N-3 fatty acids (FA) may have benefits in ICU patients. The aims were to identify whether FA status is altered in critical illness and to evaluate the effect of supplemental intravenous n-3 FA on plasma FA status and clinical outcome in ICU patients receiving enteral nutrition. METHODS Enterally fed patients (n = 49; 60-80 years) were recruited in the first 48 h of ICU admission. Fifteen patients received n-3 FA emulsion (0.2 g/kg) over 6 h for 3 consecutive days, and 34 patients did not (control). Samples were collected before supplementation, and 24 and 72 h after the third infusion. Nineteen healthy elderly subjects were also studied; they gave a single blood sample. FA were measured in plasma phosphatidylcholine (PC). RESULTS Critically ill patients had altered plasma PC FA compared with healthy elderly subjects. Surviving ICU patients had higher levels of docosahexaenoic acid and total n-3 FA and a lower ratio of n-6:n-3 FA in plasma PC than non-survivors. Infusion of n-3 FA increased eicosapentaenoic, docosahexaenoic and total n-3 FA, and decreased arachidonic and total n-6 FA and n-6:n-3 FA and arachidonic:eicosapentaenoic acid ratios. Gas exchange was enhanced 72 h after the third n-3 FA infusion (p = 0.001). CONCLUSIONS Critically ill patients may have altered plasma FA profiles. A higher total n-3 FA and docosahexaenoic acid content in plasma PC is associated with survival and improved gas exchange.

Fatty acids in plasma, white and red blood cells, and tissues after oral or intravenous administration of fish oil in rats.

BACKGROUND & AIMS The importance of route of administration of omega-3 (n-3) polyunsaturated fatty acids (PUFA) (oral vs intravenous (iv)) is not clear. We determined the relative concentrations of fatty acids in plasma phosphatidylcholine (PC), red blood cells (RBC), white blood cells (WBC) and several tissues after short-term oral or iv administration of soybean oil (SO) or fish oil (FO). METHODS Wistar rats (n = 6/group) received saline, FO, or SO by gavage or saline, FO based-lipid emulsion (FLE), or SO based-lipid emulsion (SLE) iv. The oils were provided at 0.2 g/kg/day for three consecutive days. The animals were sacrificed 24 h after the last administration, blood was collected for plasma, WBC and RBC separation and tissues removed. Fatty acids were analysed by gas chromatography. RESULTS FO resulted in higher eicosapentaenoic acid (EPA) in plasma PC and liver than the control. FLE resulted in higher EPA, docosahexaenoic acid (DHA) and total n-3 PUFA in plasma PC, WBC and liver than both the control and SLE groups. EPA, DHA and total n-3 PUFA were higher in the heart with FLE compared with SLE. Individual and total n-3 PUFA were higher in plasma PC, WBC, liver and heart with FLE than with FO given by gavage. CONCLUSION Short-term iv administration of n-3 PUFA appears to be more effective at increasing EPA and DHA status in plasma, WBC, liver and heart than oral administration. This might be important for rapid treatment with n-3 PUFA.

Evidence for Involvement of IL-9 and IL-22 in Cows’ Milk Allergy in Infants

Although allergic inflammation is characterized by a T helper (Th) 2-dominant immune response, the discovery of a role for new T cell subsets in inflammatory diseases has added an additional layer of complexity to the understanding of the pathogeneses of allergic diseases. We evaluated plasma cytokine profiles in infants with cows’ milk allergy (CMA), who were being treated with an elimination diet. In a prospective, randomized and controlled study, infants (aged 8.4 ± 3.9 months) with CMA were treated with an elimination diet for 120 days, which replaced cows’ milk with a hydrolysed soy protein formula (n = 26) or a free amino acid formula (n = 20). Blood samples were collected before treatment during active disease (T0) and after 120 days, when symptoms were absent (T1). Plasma cytokine concentrations were measured. Infants with CMA had higher plasma concentrations of interleukin (IL)-4 and IL-13 and lower concentrations of IL-9, IL-17A and interferon-γ, compared with healthy breast-fed infants. At T0, there was a positive correlation between blood eosinophil numbers and plasma concentrations of IL-4, IL-9, IL-17A and IL-22. Treatment with a cows’ milk elimination diet resulted in a decrease in plasma IL-4, IL-9, IL-13 and IL-22 and an increase in plasma IL-17A. We conclude that IL-4 and IL-13 are elevated in active CMA. The association of IL-9 and IL-22 with eosinophilia, and the decrease in these two cytokines with cows’ milk elimination, suggests that they both play a role in the symptoms observed in CMA and may be important targets for future interventions.

Protective effect of soybean oil- or fish oil-rich diets on allergic airway inflammation

Background The increased prevalence of asthma and allergic diseases in westernized societies has been associated with increased intake of diets rich in n-6 fatty acids (FAs) and poor in n-3 FAs. This study aimed to analyze the prophylactic effects of treatment with a soybean oil-rich diet (rich in n-6) or fish oil (rich in n-3) in an allergic airway inflammation model on lung inflammation score, leukocyte migration, T-helper cell (Th)-2 (interleukin [IL]-4, IL-5) and Th1 (interferon [IFN]-γ, tumor necrosis factor-α) cytokines, lipoxin A4, nitric oxide, bradykinin, and corticosterone levels in bronchoalveolar lavage (BAL) or lungs. Methods Male Wistar rats fed with soybean oil- or fish oil-rich diet or standard rat chow were sensitized twice with ovalbumin–alumen and challenged twice with ovalbumin aerosol. The BAL and lungs were examined 24 hours later. Results Both diets, rich in n-6 or n-3 FAs, impaired the allergic lung inflammation and reduced leukocyte migration, eosinophil and neutrophil percentages, and IL-4/IL-5/bradykinin levels in BAL and/or lungs, as well as increased the nitric oxide levels in BAL. The soybean oil-rich diet additionally increased the levels of lipoxin A4 and corticosterone in the lungs. Conclusion Data presented demonstrated that the n-6 FA-rich diet had protective effect upon allergic airway inflammation and was as anti-inflammatory as the n-3 FA-rich diet, although through different mechanisms, suggesting that both diets could be considered as complementary therapy or a prophylactic alternative for allergic airway inflammation.

Polyunsaturated Fatty Acids, Ulcerative Colitis and Cancer Prevention

Fatty acids (FA) – lipid constituents – are carboxylic acids that can be represented by the form RCO2H. Most often, the group R is a long carbon chain, unbranched and with an even number of carbon atoms and may be saturated or contain one (monounsaturated) or more double bonds (polyunsaturated) (Calder et al. 2002). Fatty acids are often referred to by their common names, but they are correctly identified by a systematic nomenclature. This nomenclature indicates first the number of carbon atoms in the hydrocarbon chain, followed by the number of double bonds, and the position of the first double bond from the terminal methyl group, which is indicated by n-9, n-7, n-6 or n -3 (Figure 1). There are two main families of polyunsaturated FA (PUFA), n-6 (or w-6) and of n-3 (or w-3) (Curi et al. 2002).