Administration Of Fatty Acids Research Articles

Skeletal effects of the peroxisome proliferator activated receptor (PPAR)pan agonist tetradecylthioacetic acid (TTA) in rats

A single administration of 3-thiadicarboxylic and tetradecylthioacetic acids stimulates both mitochondrial and peroxisomal β-oxidation and lowers plasma triacylglycerol levels. An increased rate of mitochondrial β-oxidation and carnitine palmitoyltransferase activity was established after 3 h and this was accompanied by a lowering of plasma triacylglycerol. Peroxisomal β-oxidation, however, remained unchanged up to 8 h and was significantly increased after 12 h. These results suggest that after a single administration of 3-thia fatty acids mitochondrial β-oxidation precedes peroxisomal β-oxidation. Furthermore, they show that the observed triacylglycerol-lowering effect, which is established early (3–4 h) after the administration of 3-thia fatty acids, is initially due to an increased mitochondrial β-oxidation.

Scientific Opinion on the substantiation of health claims related to gamma linolenic acid and maintenance of joints (ID 494, 637, 1774, 2098), weight maintenance following weight loss (ID 496), maintenance of peripheral blood flow (ID 638), maintenance of normal blood pressure (ID 1771), maintenance of normal blood cholesterol concentrations (ID 1771) and maintenance of bone (ID 1774) pursuant to Article

Scientific Opinion on the substantiation of health claims related to gamma linolenic acid and maintenance of joints (ID 494, 637, 1774, 2098), weight maintenance following weight loss (ID 496), maintenance of peripheral blood flow (ID 638), maintenance of normal blood pressure (ID 1771), maintenance of normal blood cholesterol concentrations (ID 1771) and maintenance of bone (ID 1774) pursuant to Article

Administration of Omega-3 Fatty Acids Reduces Positive Tender Point Count in Chronic Musculoskeletal Pain Patients

Dietary supplementation of omega-3 (n-3) is becoming increasingly popular as a complementary treatment of chronic inflammatory pain diseases. The aim of the present study was to examine the effects of short-term (35 days) n-3 supplementation on physiological/psychophysical variables and clinical symptoms in patients with musculoskeletal pain and fibromyalgia. Patients (N=41, all women), blindly assigned to two groups according to dietary supplementation (fish oil containing n-3 or sunflower oil), underwent quantitative sensory testing and completed questionnaires concerning anamnestic/epidemiological data, pain characteristics and mood. In the n-3 group there was a sharp reduction in both the arachidonic acid/eicosapentaenoic acid ratio (AA/EPA) and the number of positive tender points, but no changes occurred in superficial thermal (heat and cold) and mechanical thresholds (von Frey hairs). There were no modifications in the sunflower oil group. The supplement had no effect on blood lipids and questionnaires indicated no effect on mood, sleep problems and other pain indicators. The present results encourage clinical trials in larger samples to compare the effects of different daily amounts and treatment durations of n-3 supplementation.

Atopic dermatitis model of itching behavior in hairless mice

In atopic dermatitis (AD), severe itching and scratching not only impacts the patient's quality of life, but also exacerbates the disease; however, the precise underlying mechanisms of itching in AD remain elusive. We have previously reported a special diet-induced, mouse model of AD. This article reviews the characteristics of the model, and the chronological and pharmacological analyses of the pathology. HR-1 hairless mice fed a commercial special diet, HR-AD, but not a normal diet, showed scaly dry red skin resembling AD. To evaluate the degree of itching, spontaneous scratching was analyzed. As a result, scratching with long duration was observed in HR-AD-fed mice, as confirmed by prolongation of duration of one scratching bout. Chronological analysis of the pathologies in HR-AD-fed mice revealed that the prolonged scratching was coincident with the development of skin barrier dysfunction, while skin inflammation with recruitment of inflammatory cells, such as CD4+ T cells, eosinophils, and mast cells, and serum IgE elevations apparently followed the prolonged scratching. Epidermal nerve sprouting was detected almost coincidently with the prolonged scratching. Pharmacological analysis of the scratching behavior indicated that the prolonged scratching was suppressed by a μ-opioid receptor antagonist, but not by antihistamine, similar to AD patients. Although treatment with corticosteroid suppressed the skin inflammation, it was not effective against the prolonged scratching, the dry skin symptoms, and the epidermal nerve sprouting. Petrolatum ointment inhibited the prolonged scratching during the amelioration of skin barrier dysfunction. Furthermore, the barrier disrupted-dry skin was alleviated by oral administration of essential fatty acid, linoleic acid (LA), suggesting that LA deficiency appears to be responsible for the symptoms. Taken together, these findings suggest that skin barrier dysfunction is closely associated with the development of AD-like pruritus in this model.

Role of Short Chain Fatty Acids in Mesenteric Ischemia Reperfusion Injury in Rats

The aim of this study was to evaluate the role of short chain fatty acid administration in mesenteric ischemia reperfusion in rats. Sixteen 60-day-old male Wistar rats were divided into two groups of eight each. In group I (n=8) normal saline (10 ml/kg) was injected into the ileal lumen. Ischemia reperfusion was achieved by clamping the superior mesenteric artery (SMA) for 30 min and then releasing it for another 30 min. The ileum was harvested for histopathological examination. In group II (n=8) a mixture of short chain fatty acids (10 ml/kg) was injected into the ileal lumen. Ischemia reperfusion was achieved in a similar fashion and the ileum harvested for histopathological examination. Injury was graded according to Chiu's score. The ileum in rats from group II showed a lower injury score (0.013+/-0.354) compared to ileum from rats in group I (4.631+/-0.521), and this difference was significant (p<0.001). Short chain fatty acids significantly decreased the degree of reperfusion injury in the gut in a rat model of mesenteric ischemia reperfusion.

MP-11.10: Effect of Omega-3 Polyunsaturated Fatty Acid Supplementation on Semen Profile and Enzymatic Anti-Oxidant Capacity of Seminal Plasma in Infertile Men with Idiopathic Oligoasthenoteratospermia: A Double Blind, Placebo-Controlled, Randomized Study

The study considered two major aims: (a) to measure the changes in semen parameters, omega-3 fatty acids (FA) compositions and antioxidant activity (b) to determine if the administration of omega-3 FA affect semen quality in infertile men with idiopathic oligoasthenoteratospermia (OAT).

Your brain on fat: dietary-induced obesity impairs central nutrient sensing

the past decade has witnessed a rejuvenated interest in the ability of the central nervous system (CNS) to sense and respond to changes in nutrient availability. This interest has been driven in part by a conceptual framework where the CNS receives signals regarding nutrient availability that are

Pyruvate dehydrogenase kinase 4 expression is synergistically induced by AMP-activated protein kinase and fatty acids.

Organs are flexible as to which substrates they will use to maintain energy homeostasis. Under well-fed conditions, glucose is a preferred substrate for oxidation. During fasting, fatty acid oxidation will become a more important energy source. Glucose oxidation is decreased by fatty acids, a process in which the pyruvate dehydrogenase complex (PDH) and its regulator pyruvate dehydrogenase kinase 4 (PDK4) play important roles. It is currently unknown how energy status influences PDH activity. We show that AMP-activated protein kinase (AMPK) activation by hypoxia and AICAR treatment combined with fatty acid administration synergistically induce PDK4 expression. We provide evidence that AMPK activation modulates ligand-dependent activation of peroxisome proliferator-activated receptor. Finally, we show that this synergistic induction of PDK4 decreases cellular glucose oxidation. In conclusion, AMPK and fatty acids play a direct role in fuel selection in response to cellular energy status in order to spare glucose.

Effect of mild hypothermia on blood brain barrier disruption induced by oleic acid in rats

The blood-brain barrier (BBB) is essential for the normal function of the central nervous system. The pathological conditions induced by brain diseases including cerebral ischemia result in the alteration of BBB integrity. This alteration of BBB is relieved by mild hypothermia that has been regarded as an effective therapy for brain injury. Experimental fat embolism by intra-arterial administration of fatty acid induces reversible dysfunction of BBB and is considered as a beneficial method for the research on BBB disruption. However, the implication of hypothermia on the fatty acid-induced BBB disruption is not clear yet. In this study, we aim to investigate the effect of mild hypothermia on BBB disruption by comparing the changes of brain inflammation, free radical production, and matrix metalloproteinases (MMPs) caused by cerebral fatty acid infusion between normothermic (37°C) and hypothermic (33°C) groups. Oleic acid infusion into the carotid artery induced the increase of BBB permeability, which was inhibited by mild hypothermia. Neutrophils were infiltrated and intercellular adhesion molecule-1 (ICAM-1) expression was increased in the vascular structures in the affected brain tissue of normothermic rats at 24 hrs following oleic acid administration. Inducible nitric oxide synthase (iNOS) and nitro-tyrosine immunoreactivities were also observed in the normothermic group. The expression of matrix metalloproteinase (MMP)-2, 3, and 13 were upregulated predominantly in the oleic acid-treated brain of the normothermic rats. In mild hypothermic condition, neutrophil infiltration and ICAM-1 expression were attenuated, whereas the inductions of iNOS, nitrotyrosine and MMPs except MMP3 were not affected. Therefore, we suggest that mild hypothermia contributes to the protective effect on oleic acid-induced BBB damage via reducing neutrophil infiltration and brain inflammation.

Fatty Acid Binding Receptors and Their Physiological Role in Type 2 Diabetes

G-protein-coupled receptors (GPCRs) respond to various physiological ligands such as photons, ions, and small molecules that include amines, fatty acids, and amino acids to peptides, proteins and steroids. Therefore, this family of proteins represents an attractive target for biopharmaceutical research. The physiological role of fatty acids and other lipid molecules as important signal mediators is well studied in various metabolic pathways. Acute administration of free fatty acids (FFAs) stimulates insulin release. Conversely, chronic exposure to high levels of free fatty acids leads to impairment of beta cell function and lipotoxicity. However, the receptors through which these fatty acids and lipids act were unknown, until the identification of fatty acid binding receptors: GPR40, GPR41, GPR43, and GPR119. Based on their tissue-expression profile, and pharmacologic analysis, the fatty acid binding receptors along with lipid binding receptor GPR119 are linked to diabetes and obesity. They play a critical role in the metabolic regulation of insulin release and glucose homeostasis. In this review, the mechanism of receptor activation, pharmacology, and the physiological functions of the fatty acid binding receptors will be discussed.

The Effects of Selective COX‐2 Inhibitor/Celecoxib and Omega‐3 Fatty Acid on Matrix Metalloproteinases, TIMP‐1, and Laminin‐5γ2‐Chain Immunolocalization in Experimental Periodontitis

Matrix metalloproteinases (MMPs) play important roles in tissue-destruction mechanisms-associated periodontitis. MMP-8 and -13 are the predominant collagenases that are important in the extracellular matrix degradation in periodontal tissues. MMP-14 is a membrane-type MMP, whereas laminin-5 indicates basal membrane modification and epithelial induction. The purpose of the present study was to evaluate the effects of celecoxib and omega-3 fatty acid administration on the gingival tissue expression of MMP-8, -13, and -14, tissue inhibitor of MMP (TIMP)-1, and laminin (Ln)-5gamma2-chain in rat experimental periodontitis induced by Escherichia coli endotoxin (lipopolysaccharide [LPS]). Experimental periodontitis was induced in rats by repeated LPS injection. Fifty-one adult male Sprague-Dawley rats were divided into six study groups: saline control, LPS, LPS + celecoxib, LPS + therapeutic omega-3 (TO3), prophylactic omega-3 + LPS + omega-3 (P+TO3), and LPS + celecoxib + omega-3 fatty acid. Celecoxib and omega-3 fatty acid were given as a single agent or as combination therapy for 14 days. On day 15, all rats were sacrificed, and gingival tissues were analyzed immunohistochemically for the expression of MMP-8, -13, and -14, TIMP-1, and Ln-5gamma2-chain. Alveolar bone loss was evaluated morphometrically under a stereomicroscope. Data were tested statistically by Kruskal-Wallis and Mann-Whitney tests and Spearman correlation analysis. Alveolar bone loss was significantly higher in all study groups compared to the saline control group (all P <0.01). MMP-8 expression was significantly higher in the LPS group than in the saline group (P = 0.001). Very low expression of MMP-8 was found in the celecoxib, P+TO3, and combination groups. TO3 increased TIMP-1 expression significantly compared to the LPS group (P <0.05). Individual celecoxib and P+TO3 administration increased MMP-14 significantly compared to saline control and LPS groups (P <0.05). No significant differences were found among the study groups with regard to Ln-5gamma2-chain and MMP-13 expressions (P >0.05). Selective cyclooxygenase-2 inhibitor, prophylactic omega-3 fatty acid, and a combination of these two agents can inhibit gingival tissue MMP-8 expression. Moreover, the individual administration of therapeutic omega-3 may increase gingival TIMP-1 expression in contrast to no effect on MMP-8, -13, and -14 expressions in experimental periodontitis. These experimental findings in a rat model of LPS-induced periodontitis need to be verified by clinical human studies.

Omega-3 Free Fatty Acids for the Maintenance of Remission in Crohn Disease

Maintenance therapy for Crohn disease features the use of immunosuppressive drugs, which are associated with an increased risk of infection. Identification of safe and effective maintenance strategies is a priority. To determine whether the oral administration of omega-3 free fatty acids is more effective than placebo for prevention of relapse of Crohn disease. Two randomized, double-blind, placebo-controlled studies (Epanova Program in Crohn's Study 1 [EPIC-1] and EPIC-2) conducted between January 2003 and February 2007 at 98 centers in Canada, Europe, Israel, and the United States. Data from 363 and 375 patients with quiescent Crohn disease were evaluated in EPIC-1 and EPIC-2, respectively. Patients with a Crohn's Disease Activity Index (CDAI) score of less than 150 were randomly assigned to receive either 4 g/d of omega-3 free fatty acids or placebo for up to 58 weeks. No other treatments for Crohn disease were permitted. Clinical relapse, as defined by a CDAI score of 150 points or greater and an increase of more than 70 points from the baseline value, or initiation of treatment for active Crohn disease. For EPIC-1, 188 patients were assigned to receive omega-3 free fatty acids and 186 patients to receive placebo. Corresponding numbers for EPIC-2 were 189 and 190 patients, respectively. The rate of relapse at 1 year in EPIC-1 was 31.6% in patients who received omega-3 free fatty acids and 35.7% in those who received placebo (hazard ratio, 0.82; 95% confidence interval, 0.51-1.19; P = .30). Corresponding values for EPIC-2 were 47.8% and 48.8% (hazard ratio, 0.90; 95% confidence interval, 0.67-1.21; P = .48). Serious adverse events were uncommon and mostly related to Crohn disease. In these trials, treatment with omega-3 free fatty acids was not effective for the prevention of relapse in Crohn disease. clinicaltrials.gov Identifiers: EPIC-1: NCT00613197, EPIC-2: NCT00074542.

Effekt eines Omega-3- Konzentrats auf das Lipidprofil

Eine große Anzahl epidemiologischer, experimenteller und klinischer Daten belegt die ausgeprägte Wirkung von Omega-3-Fettsäuren auf mehrere Risikofaktoren der koronaren Herzkrankheit (KHK) und ihre Bedeutung für deren Primär- und Sekundärprävention.

Significance of omega-3 polyunsaturated fatty acid administration in the therapeutic approach of depression in hemodialysis patients

According to various reports and clinical studies mentaldisorders represent a frequent sequela of chronic diseases.In end stage renal disease, in particular, mood disordersand more specifically major depression is met with a fre-quency of 20-30% and is the most widely acknowledgedabnormality [1]. As a consequence, overall quality of lifeas well as treatment compliance is severely impaired [2].Omega-3 (Ω3) polyunsaturated fatty acids (PUFAs) havebeen shown to reduce the risk and to treat mental disor-ders including depression [3]. However, evidence to date,remains obscure and recommendations must be givenwith caution [4]. The aim of the present study was to eval-uate the significance of Ω3 administration in the treat-ment of depressive maintenance hemodialysis (HD)patients.

Effect of Some Natural Products Either Alone or in Combination on Gastritis Induced in Experimental Rats

Gastritis, an inflammatory state in gastric mucosa, can be induced experimentally in various ways. The present study considered the iodoacetamide model (Iodo). Omega-3 fatty acids (fish oil), black seed oil, and curcuminoids (natural products) in addition to omeprazole (synthetic proton-pump inhibitor) were tested. Supplementation of 0.1% iodoacetamide to drinking water of experimental rats for two consecutive weeks resulted in: (i) increased serum nitric oxide (NO) and gastrin, and decreased pepsinogen, (ii) depletion of gastric mucosal glutathione (GSH), and (iii) increased gastric mucosal lipid peroxidation (MDA), but failed to affect gastric mucosal myeloperoxidase (MPO) activity. Histological examination showed marked neutrophilic infiltration after 1 week of iodoacetamide administration and shedding of apical cell layer with pale edematous vacuolated gastric gland cells and thickening of muscularis mucosa after 2 weeks of iodoacetamide intake. Individual administration of omega-3 fatty acids 12 mg/kg, black seed oil 50 mg/kg, and curcuminoids 50 mg/kg body weight orally daily for 3 weeks decreased MDA, gastrin, and NO, and normalized mucosal GSH but failed to affect serum pepsinogen level. Combined administration of these natural products for 3 weeks normalized MPO activity, and other effects were nearly the same as with individual use. Omeprazole administration 30 mg/kg body weight orally daily for 3 weeks induced a similar response except for an observed increase in serum gastrin and pepsinogen levels.

Inhibition of Foxo1 Protects Pancreatic Islet β-Cells Against Fatty Acid and Endoplasmic Reticulum Stress–Induced Apoptosis

beta-Cells are particularly susceptible to fatty acid-induced apoptosis associated with decreased insulin receptor/phosphatidylinositol-3 kinase/Akt signaling and the activation of stress kinases. We examined the mechanism of fatty acid-induced apoptosis of mouse beta-cells especially as related to the role played by endoplasmic reticulum (ER) stress-induced Foxo1 activation and whether decreasing Foxo1 activity could enhance cell survival. Mouse insulinoma (MIN6) cells were administered with fatty acids, and the role of Foxo1 in mediating effects on signaling pathways and apoptosis was examined by measuring Foxo1 activity and using dominant-negative Foxo1. Increasing fatty acid concentrations (100-400 micromol/l palmitate or oleate) led to early Jun NH(2)-terminal kinase (JNK) activation that preceded induction of ER stress markers and apoptosis. Foxo1 activity was increased with fatty acid administration and by pharmacological inducers of ER stress, and this increase was prevented by JNK inhibition. Fatty acids induced nuclear localization of Foxo1 at 4 h when Akt activity was increased, indicating that FoxO1 activation was not mediated by JNK inhibition of Akt. In contrast, fatty acid administration for 24 h was associated with decreased insulin signaling. A dominant-negative Foxo1 adenovirus (Adv-DNFoxo) conferred cells with protection from ER stress and fatty acid-mediated apoptosis. Microarray analysis revealed that fatty acid induction of gene expression was in most cases reversed by Adv-DNFoxo, including the proapoptotic transcription factor CHOP (C/EBP [CCAAT/enhancer binding protein] homologous protein). Early induction of JNK and Foxo1 activation plays an important role in fatty acid-induced apoptosis. Expressing a dominant-negative allele of Foxo1 reduces expression of apoptotic and ER stress markers and promotes beta-cell survival from fatty acid and ER stress, identifying a potential therapeutic target for preserving beta-cells in type 2 diabetes.

Effects of n-3 polyunsaturated fatty acids in subjects with nonalcoholic fatty liver disease

Long-chain polyunsaturated fatty acid omega-3 levels are decreased in the hepatic tissue of patients with nonalcoholic fatty liver disease. Polyunsaturated fatty acids are negative regulators of hepatic lipogenesis and attenuate the inflammatory response in mice. To investigate whether polyunsaturated fatty acid may be effective in the treatment of nonalcoholic fatty liver disease. Forty patients with nonalcoholic fatty liver disease were randomized into two groups for treatment of 6 months duration. Group DP (n=20) received an AHA recommended diet and polyunsaturated fatty acid 2g/day; Group D (n=20) received only the AHA regular diet. Outcome measurements were fatty liver assessed by abdominal ultrasound, liver aminotransferase and tumour necrosis factor-alpha serum levels, and insulin resistance assessed by HOMA(IR). After 6 months of treatment, the DP group displayed a decrease in alanine aminotransferase levels (p<0.01), as well as in triglyceride levels (p<0.01), serum tumour necrosis factor-alpha levels (p<0.05) and in HOMA(IR) (p<0.05). In the D group, no significant modification was observed. In the DP group, complete fatty liver regression was observed in 33.4% of the patients, and an overall reduction in 50%. In contrast, no patient achieved complete regression in the D group, whereas some amount of reduction occurred in 27.7% of the patients; the remaining 72.2% did not change. Our results indicate that alanine aminotransferase, triglyceride and serum tumour necrosis factor-alpha levels, as well as fatty liver improved after polyunsaturated fatty acid administration.

Omega-3 Fatty Acid Deficiency in Sickle Cell Disease Correlates with Clinical Severity and Has Therapeutic Implications.

Background: Clinical illness in SCD results not only from the β-globin gene mutation, but also from other genetic and environmental factors acting in concert. The biological basis of individual variation in the severity of SCD is not fully understood. Our previous study revealed that WBCs from people with severe SCD express high levels of the adhesion molecules L-selectin (CD62L) and αMβ2 integrin (CD11a/18) in steady state. These cell membrane proteins mediate leukocyte adherence to vascular endothelium and facilitate vaso-occlusion: a fundamental pathological process in SCD. The lipid composition of cell membranes affects the level of expression of adhesion molecules on the membrane, its structural integrity and function. Abnormalities of plasma and erythrocyte lipids in SCD had been recognised. However, there is little information on lipid composition of leukocyte and platelet membranes in SCD, and its relationship with clinical severity.Objectives: To analyse the membrane fatty acid (FA) composition of blood mononuclear cells and platelets in SCD, find out if the degree of lipid abnormalities in RBCs affects the Hb level, and whether differences in FA composition of blood cells relate to clinical severity.Study Design & Methods: The fatty acid (FA) composition of blood cells and plasma in 71 HbSS and 9 HbSC steady-state patients were compared with those of 58 healthy, racially-matched, HbAA controls with similar age and sex distribution. To minimise the confounding effects of differences in dietary patterns, patients were compared with controls living in the same environment. We excluded cigarette smokers, SCD patients with other diseases, HbF levels ≥ 10%, and blood transfusion or pregnancy in the previous 3 months. Hb genotype was determined by electrophoresis or High Performance Liquid Chromatography. The manifestations of SCD were ascertained in each patient by clinical assessment. FA composition of cell membranes and plasma was analysed as described by Folch et al. The statistical package SPSS for Windows (SPSS Ltd, Woking, UK) was used for data analyses.Results: Mononuclear leukocytes, platelets, plasma and erythrocytes of SCD patients showed deficiency of omega-3 FA relative to matched HbAA controls (p< 0.05). Steady-state Hb level in SCD patients showed strong direct correlation with the proportion of omega-3 FA in RBCs (p< 0.01). HbSS patients had significantly lower amounts of omega-3 FA compared with HbSC individuals in erythrocytes (p< 0.001) and plasma (p< 0.05). The deficiency of omega-3 FA was significantly greater in patients with complications of SCD in comparison to those who had none (p< 0.005).Therapeutic Implications: The findings suggest that steady-state Hb level in SCD patients might be improved by administration of omega-3 FA. That HbSC patients are also deficient in omega-3 FA suggests that they might derive clinical benefit from therapy with these naturally occurring substances; as previously demonstrated in a pilot clinical trial involving HbSS individuals. Considering that omega-3 fatty acids are generally consumed as food across the world, more widely available and affordable, safer and have less side-effects compared to hydroxyurea or blood transfusion, it is appropriate to assess their efficacy in SCD in a large clinical trial.

Anti-Arrhythmic Properties of N-3 Poly-Unsaturated Fatty Acids (n-3 PUFA)

Omega-3 fatty acids (Poly-Unsaturated Fatty Acids or PUFA n-3) have been initially found to reduce plasma levels of triglycerides and to increase levels of high-density lipoprotein in patients with marked hypertriglyceridemia. However, in both bench research studies and clinical trials, omega-3 fatty acid intake has recently been associated with an anti-arrhythmic efficacy. At experimental level, n-3 PUFA administration produces several actions on ionic channels regulating transmembrane action potential. At clinical level, the most significant finding was the reduction in the incidence of sudden death in survivors of MI in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevention trial and the subsequent recommendation for administration of fish oil as part of the post-infarction regimen in European guidelines. More recently, Omega-3 fatty acids administration has been associated with a lower incidence of atrial fibrillation in patients who underwent cardiac surgery. Contrasting results have been instead reported in patients with implantable cardioverter defibrillators. This article reviews in detail the basic and clinical research studies of fish oil as an anti-arrhythmic entity, the types of arrhythmias that have been beneficially affected by fish oil administration, and the presumed and known mechanisms by which the beneficial actions are exerted.

Long-term n-3 polyunsaturated fatty acids administration ameliorates arteriosclerosis by modulating T-cell activity in a rat model of small intestine transplantation

Background Fish oil, rich in n-3 polyunsaturated fatty acids (n-3 PUFAs), has been found to reduce graft rejection and increase allografts survival. But these studies mainly focused on acute rejection. We imitated long-term fish oil administration to investigate the effects of n-3 PUFAs on graft arteriosclerosis, and T cells in a rat model of small intestine transplantation. Methods From 2 weeks pre-transplantation to the 60th day post-transplantation, the Lewis rats were supplemented by gavage with phosphate buffer saline, corn oil and fish oil respectively. Total small intestine was heterotopically transplanted from F344 to Lewis rat. Graft arteriosclerosis was assessed by histological grading of intimal thickening. The expression of CD25 and CD154, IL-2 level, and NF-κB activation in T cells were analyzed by western blotting, ELISA, and electrophoretic mobility shift assay respectively. Results Compared with corn oil, graft arteriosclerosis was ameliorated by fish oil significantly. The expression of CD25 and CD154, IL-2 level, and NF-κB activation were markedly reduced by fish oil. Conclusions Long-term n-3 PUFAs administration pre- and post-transplantation could inhibit T-cell activity by reducing CD154 expression and NF-κB activation, which might contribute to amelioration of graft arteriosclerosis.