RESUMO
This study aimed to evaluate the levels of eicosanoids derived from arachidonic acid (ARA) in the lungs of asthmatic rats supplemented with fish oil. The present data gives insight into the action of fish oil in asthma, related to its inability to modify the contractile capacity of tracheal smooth muscle reported previously in a model of asthma in rats. Male Wistar rats were supplemented daily with 1 g of fish oil/kg of body weight for 21 days. They were exposed to ovalbumin (OVA) after previous sensitization with OVA to induce asthma. Pulmonary levels of five eicosanoids were measured using immunoassay kits: PGE2, TXB2, LTB4, LXA4, and 8-iso PGF2α. In asthmatic rats, supplementation with fish oil resulted in lower concentrations of lung eicosanoids produced by cyclooxygenase-2 and 15-lipoxygenase: PGE2, TXB2, and LXA4, respectively. Fish oil supplementation also decreased the non-enzymatically produced eicosanoid 8-iso PGF2α. Fish oil supplementation did not affect LTB4, a metabolite of 5-lipoxygenase. The limited efficacy of fish oil supplementation in asthmatic rats is associated with a lack of action in reducing the levels of LTB4 in the lungs. Thus, fish oil differentially modulates the concentrations of eicosanoids derived from ARA via specific pathways in an animal model of asthma.
RESUMO
BACKGROUND: Studies suggest that the ingestion of fish oil (FO), a source of the omega-3 polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), can reduce the deleterious side-effects of chemotherapy. The aim of this randomised clinical trial was to evaluate the effect of supplementation with oral FO for 9 weeks on nutritional parameters and inflammatory nutritional risk in patients with haematological malignancies during the beginning of chemotherapy. METHODS: Twenty-two patients with leukaemia or lymphoma were randomised to the unsupplemented group (UG) (n = 13) or supplemented group (SG) (n = 9). SG received 2 g/day of fish oil for 9 weeks. Nutritional status, serum acute-phase proteins and plasma fatty acids were evaluated before (T0) and after (T1) the intervention period. Data were analysed using two models; model 1, comprising data from all patients included in the study, and model 2, comprising data from UG patients with no increase in the proportions of EPA and DHA in plasma and data from SG patients showing an at least 100% increase in plasma EPA and DHA. RESULTS: SG showed an increased plasma proportion of EPA and DHA in both models. In model 2, C-reactive protein (CRP) and CRP/albumin ratio showed larger reductions in the SG. Overall long-term survival in both models (465 days after the start of the chemotherapy) was higher in the group ingesting fish oil (P < 0.05). CONCLUSIONS: These findings indicate an improved nutritional-inflammatory risk and potential effects on long-term survival in patients with haematological malignancies supplemented with FO during the beginning of chemotherapy.
Assuntos
Suplementos Nutricionais , Óleos de Peixe/administração & dosagem , Neoplasias Hematológicas/tratamento farmacológico , Adolescente , Adulto , Idoso , Antropometria , Proteína C-Reativa/metabolismo , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/sangue , Feminino , Neoplasias Hematológicas/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Albumina Sérica/metabolismo , Adulto JovemRESUMO
We recently reported that iron supplementation increased respiratory morbidity in iron deficient South African children. This increase, however, was attenuated when iron was provided in combination with a mixture of DHA/EPA. To explore potential underlying mechanisms, we examined the effects of iron and DHA/EPA, alone and in combination, on plasma lipid-derived immune modulator concentrations and related gene expression in peripheral blood mononuclear cells (PBMC). DHA/EPA decreased inflammatory 12-hydroxyeicosatetraenoic acid and tended to increase anti-inflammatory and pro-resolving 17-hydroxydocosahexaenoic acid (17-HDHA), while iron decreased 17-HDHA. However, in combination with iron, the anti-inflammatory effect of DHA/EPA was maintained. These biochemical changes may explain the prevention of iron-induced respiratory morbidity that we observed when iron was supplemented in combination with DHA/EPA during the 8.5 month randomised controlled trial and might lead to a safer approach of delivering iron supplementation. The study was registered at clinicaltrials.gov as NCT01092377.
Assuntos
Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácido Eicosapentaenoico/uso terapêutico , Deficiências de Ferro , Ferro/uso terapêutico , Criança , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Método Duplo-Cego , Ácido Eicosapentaenoico/administração & dosagem , Feminino , Humanos , Ferro/administração & dosagem , Masculino , Estresse Oxidativo/efeitos dos fármacos , América do SulRESUMO
Episodes of acute exacerbation are the major clinical feature of asthma and therefore represent an important focus for developing novel therapies for this disease. There are many reports that the n-3 fatty acids found in fish oil exert anti-inflammatory effects, but there are few studies of the action of fish oil on airway smooth muscle (ASM) function. In the present investigation, we evaluated the effect of fish oil supplementation on smooth muscle force of contraction in ovalbumin-induced asthmatic Wistar rats, and its consequences on static lung compliance, mucus production, leukocyte chemotaxis and production of proinflammatory cytokines. Fish oil supplementation suppressed the infiltration of inflammatory cells into the lung in asthmatic animals (2.04 ± 0.19 × 10(6) cells vs. 3.33 ± 0.43 × 10(6) cells in the control asthmatic group; P < 0.05). Static lung compliance increased with fish oil supplementation in asthmatic rats (0.640 ± 0.053 mL/cm H2O vs. 0.399 ± 0.043 mL/cm H2O; P < 0.05). However, fish oil did not prevent asthma-associated lung eosinophilia and did not affect the concentrations of tumor necrosis factor-α and interleukin-1ß in lung tissue or the proportion of the airways obliterated with mucus. Fish oil had no effect on the force of contraction in asthmatic rats in response to acetylcholine (3.026 ± 0.274 mN vs. 2.813 ± 0.364 mN in the control asthmatic group). In conclusion, although fish oil exerts some benefits in this model of asthma, its effectiveness appears to be limited by an inefficient action on airway smooth muscle function.
Assuntos
Asma/fisiopatologia , Óleos de Peixe/farmacologia , Músculo Liso/efeitos dos fármacos , Traqueia/efeitos dos fármacos , Acetilcolina/farmacologia , Análise de Variância , Animais , Asma/induzido quimicamente , Líquido da Lavagem Broncoalveolar/citologia , Broncodilatadores/farmacologia , Suplementos Nutricionais , Eosinófilos/efeitos dos fármacos , Eosinófilos/patologia , Óleos de Peixe/administração & dosagem , Técnicas In Vitro , Interleucina-1beta/metabolismo , Isoproterenol/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Complacência Pulmonar/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Linfócitos/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Músculo Liso/fisiopatologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Ovalbumina , Ratos , Ratos Wistar , Traqueia/fisiopatologia , Fator de Necrose Tumoral alfa/metabolismo , Vasodilatadores/farmacologiaRESUMO
Lipids used in nutritional support of surgical or critically ill patients have been based on soybean oil, which is rich in the n-6 fatty acid linoleic acid (18:2n-6). Linoleic acid is the precursor of arachidonic acid (20:4n-6). In turn, arachidonic acid in cell membrane phospholipids is the substrate for the synthesis of a range of biologically active compounds (eicosanoids) including prostaglandins, thromboxanes, and leukotrienes. These compounds can act as mediators in their own right and can also act as regulators of other processes, such as platelet aggregation, blood clotting, smooth muscle contraction, leukocyte chemotaxis, inflammatory cytokine production, and immune function. There is a view that an excess of n-6 fatty acids should be avoided since this could contribute to a state where physiological processes become dysregulated. One alternative is the use of fish oil. The rationale of this latter approach is that fish oil contains long chain n-3 fatty acids, such as eicosapentaenoic acid. When fish oil is provided, eicosapentaenoic acid is incorporated into cell membrane phospholipids, partly at the expense of arachidonic acid. Thus, there is less arachidonic acid available for eicosanoid synthesis. Hence, fish oil decreases production of prostaglandins like PGE2 and of leukotrienes like LTB4. Thus, n-3 fatty acids can potentially reduce platelet aggregation, blood clotting, smooth muscle contraction, and leukocyte chemotaxis, and can modulate inflammatory cytokine production and immune function. These effects have been demonstrated in cell culture, animal feeding and healthy volunteer studies. Fish oil decreases the host metabolic response and improves survival to endotoxin in laboratory animals. Recently clinical studies performed in various patient groups have indicated benefit from this approach.
Assuntos
Estado Terminal/terapia , Ácidos Graxos Ômega-3/uso terapêutico , Inflamação/tratamento farmacológico , Nutrição Parenteral/métodos , Animais , Ácido Araquidônico/metabolismo , Modelos Animais de Doenças , Ácido Eicosapentaenoico/metabolismo , Ácido Eicosapentaenoico/uso terapêutico , Endotoxemia/metabolismo , Endotoxemia/terapia , Ácidos Graxos Ômega-3/imunologia , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos Insaturados/uso terapêutico , Humanos , Sistema Imunitário/efeitos dos fármacos , Inflamação/imunologia , Inflamação/metabolismoRESUMO
Lipids used in nutritional support of surgical or critically ill patients have been based on soybean oil, which is rich in the n-6 fatty acid linoleic acid (18:2n-6). Linoleic acid is the precursor of arachidonic acid (20:4n-6). In turn, arachidonic acid in cell membrane phospholipids is the substrate for the synthesis of a range of biologically active compounds (eicosanoids) including prostaglandins, thromboxanes, and leukotrienes. These compounds can act as mediators in their own right and can also act as regulators of other processes, such as platelet aggregation, blood clotting, smooth muscle contraction, leukocyte chemotaxis, inflammatory cytokine production, and immune function. There is a view that an excess of n-6 fatty acids should be avoided since this could contribute to a state where physiological processes become dysregulated. One alternative is the use of fish oil. The rationale of this latter approach is that fish oil contains long chain n-3 fatty acids, such as eicosapentaenoic acid. When fish oil is provided, eicosapentaenoic acid is incorporated into cell membrane phospholipids, partly at the expense of arachidonic acid. Thus, there is less arachidonic acid available for eicosanoid synthesis. Hence, fish oil decreases production of prostaglandins like PGE2 and of leukotrienes like LTB4. Thus, n-3 fatty acids can potentially reduce platelet aggregation, blood clotting, smooth muscle contraction, and leukocyte chemotaxis, and can modulate inflammatory cytokine production and immune function. These effects have been demonstrated in cell culture, animal feeding and healthy volunteer studies. Fish oil decreases the host metabolic response and improves survival to endotoxin in laboratory animals. Recently clinical studies performed in various patient groups have indicated benefit from this approach
Assuntos
Humanos , Animais , Estado Terminal , Ácidos Graxos Ômega-3 , Inflamação , Nutrição Parenteral , Ácidos Graxos Ômega-3 , Ácidos Graxos Insaturados , Óleos de Peixe , Sistema Imunitário , InflamaçãoRESUMO
The proliferation of concanavalin A (Con A)-stimulated rat lymphocytes was markedly inhibited by phosphatidylcholine containing arachidonic and stearic acids (PC(A-S)), but not by phosphatidylcholine containing oleic and stearic acids or phosphatidylinositol containing arachidonic and stearic acids. The concentration of PC(A-S) which inhibited Con A-stimulated proliferation by 50% was 31 microM and near total inhibition was observed at 154 microM . Phosphatidylserine containing only oleic acid enhanced proliferation by 37% at a concentration of 31 microM , but phosphatidylethanolamine and phosphatidylcholine containing only oleic acid did not affect proliferation at this concentration. It is concluded that both the head group and the fatty acid composition contribute to the influence of phospholipids on lymphocyte proliferation. The effects of PC(A-S) on T-lymphocyte responses were investigated further. In parallel with the inhibition of proliferation PC(A-S) caused a concentration-dependent decrease in the production of the Th1-type cytokines interleukin (IL)-2 and interferon (IFN)-gamma; inhibition of cytokine production was >85% at the highest concentration of PC(A-S) used (154 microM ). Production of the Th2-type cytokines IL-4 and IL-10 was not affected. The possible role of prostaglandins in mediating the effects of PC(A-S) was examined by adding indomethacin into the medium and the participation of lipid peroxidation was examined by adding vitamin E and vitamin C. Indomethacin and vitamin E did not affect the inhibition caused by PC(A-S) but vitamin C caused a partial reversal. It is concluded that inhibition of T-lymphocyte proliferation by phospholipids involves both the head group and the fatty acyl chains, that this inhibition is not mediated by prostaglandins but may involve some form of oxidant stress and that some phospholipids (e.g., PC(A-S)) can markedly influence cytokine profiles.
Assuntos
Ácido Araquidônico/farmacologia , Interferon gama/biossíntese , Interleucina-2/biossíntese , Linfócitos/efeitos dos fármacos , Fosfatidilcolinas/farmacologia , Animais , Ácido Araquidônico/análise , Ácido Ascórbico/farmacologia , Concanavalina A , Indometacina/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Lipopolissacarídeos , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/metabolismo , Masculino , Fosfatidilcolinas/química , Ratos , Ratos Wistar , Timidina/metabolismo , Trítio , Vitamina E/farmacologiaRESUMO
1. Fish oils are rich in the long-chain n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids. Linseed oil and green plant tissues are rich in the precursor fatty acid, alpha-linolenic acid (18:3n-3). Most vegetable oils are rich in the n-6 PUFA linoleic acid (18:2n-6), the precursor of arachidonic acid (20:4n-6). 2. Arachidonic acid-derived eicosanoids such as prostaglandin E2 are pro-inflammatory and regulate the functions of cells of the immune system. Consumption of fish oils leads to replacement of arachidonic acid in cell membranes by eicosapentaenoic acid. This changes the amount and alters the balance of eicosanoids produced. 3. Consumption of fish oils diminishes lymphocyte proliferation, T-cell-mediated cytotoxicity, natural killer cell activity, macrophage-mediated cytotoxicity, monocyte and neutrophil chemotaxis, major histocompatibility class II expression and antigen presentation, production of pro-inflammatory cytokines (interleukins 1 and 6, tumour necrosis factor) and adhesion molecule expression. 4. Feeding laboratory animals fish oil reduces acute and chronic inflammatory responses, improves survival to endotoxin and in models of autoimmunity and prolongs the survival of grafted organs. 5. Feeding fish oil reduces cell-mediated immune responses. 6. Fish oil supplementation may be clinically useful in acute and chronic inflammatory conditions and following transplantation. 7. n-3 PUFAs may exert their effects by modulating signal transduction and/or gene expression within inflammatory and immune cells.
Assuntos
Anti-Inflamatórios/farmacologia , Gorduras Insaturadas na Dieta/farmacologia , Ácidos Graxos Insaturados/farmacologia , Óleos de Peixe/farmacologia , Sistema Imunitário/efeitos dos fármacos , Animais , Moléculas de Adesão Celular/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Divisão Celular , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Gorduras Insaturadas na Dieta/metabolismo , Ácidos Graxos Insaturados/biossíntese , Ácidos Graxos Insaturados/metabolismo , Óleos de Peixe/metabolismo , Humanos , Sistema Imunitário/citologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/metabolismo , Linfócitos/citologia , Macrófagos/citologia , Transplante de ÓrgãosRESUMO
The effect of oat bran- (OBD) and wheat bran-enriched diets (WBD) on fatty acid composition of neutral lipids and phospholipids of rat lymphocytes and macrophages was investigated. In neutral lipids of lymphocytes, OBD reduced the proportion of palmitoleic acid (48%), whereas WBD reduced by 43% palmitoleic acid and raised oleic (18%), linoleic (52%), and arachidonic (2.5-fold) acids. In neutral lipids of macrophages, OBD increased palmitic (16%) and linoleic (29%) acids and slightly decreased oleic acid (15%). The effect of WBD, however, was more pronounced: It reduced myristic (60%), stearic (24%) and arachidonic (63%) acids, and it raised palmitic (30%) and linoleic (2.3-fold) acids. Neither OBD nor WBD modified the composition of fatty acids in phospholipids of lymphocytes. In contrast, both diets had a marked effect on composition of fatty acids in macrophage phospholipids. OBD raised the proportion of myristic (42%) and linoleic (2.4-fold) acids and decreased that of lauric (31%), palmitoleic (43%), and arachidonic (29%) acids. WBD increased palmitic (18%) and stearic (23%) acids and lowered palmitoleic (35%) and arachidonic (78%) acids. Of both cells, macrophages were more responsive to the effect of the fiber-rich diets on fatty acid composition of phospholipids. The high turnover of fatty acids in macrophage membranes may explain the differences between both cells. The modifications observed due to the effects of both diets were similar in few cases: an increase in palmitic and linoleic acids of total neutral lipids occurred and a decrease in palmitoleic and arachidonic acids of phospholipid. Therefore, the mechanism involved in the effect of both diets might be different.
Assuntos
Fibras na Dieta/farmacologia , Ácidos Graxos/análise , Linfócitos/química , Macrófagos/química , Animais , Avena/química , Dieta , Ácidos Graxos/sangue , Ácidos Graxos/metabolismo , Lipídeos/química , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Fosfolipídeos/química , Ratos , Ratos Wistar , Solubilidade , Triticum/químicaRESUMO
1. Lymphocytes play an important role in cell-mediated immunity and have been implicated in inflammatory and autoimmune diseases. 2. Unsaturated fatty acids, including oleic, linoleic, alpha-linolenic, arachidonic, eicosapentaenoic and docosahexaenoic acids, inhibit mitogen-stimulated lymphocyte proliferation in vitro. The inhibition of proliferation is dependent upon the concentration of fatty acid, the time during culture of fatty acid addition, the duration of exposure of the cells to the fatty acid and the chain length and degree of unsaturation of the fatty acid. 3. Unsaturated fatty acids suppress production of the immunoregulatory cytokine interleukin-2 by lymphocytes in vitro. 4. Triacylglycerols containing unsaturated fatty acids inhibit lymphocyte proliferation and natural killer cell activity in vitro. 5. Feeding weanling rats diets containing olive oil, evening primrose oil or fish oil results in suppression of lymphocyte proliferation. 6. Preliminary studies indicated that supplementation of the diet of healthy humans with fish oil-containing capsules suppresses lymphocyte proliferation and interleukin-2 production. 7. These effects, along with inhibitory effects upon the functions of other cells involved in the immune response, in particular monocytes and macrophages, indicate that certain unsaturated fatty acid-containing oils (particularly evening primrose oil and fish oil) may be of benefit in the treatment of inflammatory and autoimmune diseases.