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1.
Mucosal Immunol ; 13(3): 481-492, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31907365

RESUMO

Lipid mediators derived from omega (n)-3 and n-6 long-chain polyunsaturated fatty acids (LCPUFA) play key roles in bronchoconstriction, airway inflammation, and resolution processes in asthma. This study compared the effects of dietary supplementation with either a combination of LCPUFAs or eicosapentaenoic acid (EPA) alone to investigate whether the combination has superior beneficial effects on the outcome of asthmatic mice. Mice were sensitized with house dust mite (HDM) extract, and subsequently supplemented with either a combination of LCPUFAs or EPA alone in a recall asthma model. After the final HDM and LCPUFA administration, airway hyperresponsiveness (AHR), bronchoalveolar lavages, and lung histochemistry were examined. Lipid mediator profiles were determined by liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). The LCPUFA combination reduced AHR, eosinophilic inflammation, and inflammatory cytokines (IL-5, IFN-γ, and IL-6) in asthmatic mice, whereas EPA enhanced inflammation. The combination of LCPUFAs was more potent in downregulating EPA-derived LTB5 and LTC5 and in supporting DHA-derived RvD1 and RvD4 (2.22-fold and 2.58-fold higher levels) than EPA alone. Ex vivo experiments showed that LTB5 contributes to granulocytes' migration and M1-polarization in monocytes. Consequently, the LCPUFA combination ameliorated airway inflammation by inhibiting adverse effects of EPA and promoting pro-resolving effects supporting the lipid mediator-dependent resolution program.


Assuntos
Anti-Inflamatórios/administração & dosagem , Asma/etiologia , Ácido Eicosapentaenoico/efeitos adversos , Ácidos Graxos Insaturados/administração & dosagem , Alérgenos/imunologia , Animais , Anti-Inflamatórios/química , Asma/tratamento farmacológico , Asma/metabolismo , Asma/patologia , Biópsia , Vias Biossintéticas/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Ciclo-Oxigenase 2/metabolismo , Suplementos Nutricionais , Modelos Animais de Doenças , Ácidos Graxos Insaturados/química , Imunização , Imuno-Histoquímica , Leucotrienos/biossíntese , Camundongos , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória/tratamento farmacológico , Hipersensibilidade Respiratória/etiologia , Hipersensibilidade Respiratória/metabolismo , Hipersensibilidade Respiratória/patologia
2.
Thromb Haemost ; 114(2): 289-96, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25832443

RESUMO

Platelets from patients with type 2 diabetes are characterised by hyperactivation and high level of oxidative stress. Docosahexaenoic acid (DHA) may have beneficial effects on platelet reactivity and redox status. We investigated whether moderate DHA supplementation, given as a triglyceride form, may correct platelet dysfunction and redox imbalance in patients with type 2 diabetes. We conducted a randomised, double-blind, placebo-controlled, two-period crossover trial (n=11 post-menopausal women with type 2 diabetes) to test the effects of 400 mg/day of DHA intake for two weeks on platelet aggregation, markers of arachidonic acid metabolism, lipid peroxidation status, and lipid composition. Each two week-period was separated from the other by a six-week washout. Daily moderate dose DHA supplementation resulted in reduced platelet aggregation induced by collagen (-46.5 %, p< 0.001), and decreased platelet thromboxane B2 (-35 %, p< 0.001), urinary 11-dehydro-thromboxane B2 (-13.2 %, p< 0.001) and F2-isoprostane levels (-19.6 %, p< 0.001) associated with a significant increase of plasma and platelet vitamin E concentrations (+20 % and +11.8 %, respectively, p< 0.001). The proportions of DHA increased both in plasma lipids and in platelet phospholipids. After placebo treatment, there was no effect on any parameters tested. Our findings support a significant beneficial effect of low intake of DHA on platelet function and a favourable role in reducing oxidative stress associated with diabetes.


Assuntos
Antioxidantes/uso terapêutico , Plaquetas/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/uso terapêutico , Lipídeos/sangue , Estresse Oxidativo/efeitos dos fármacos , Administração Oral , Antioxidantes/farmacologia , Ácido Araquidônico/metabolismo , Plaquetas/química , Colágeno/farmacologia , Estudos Cross-Over , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/urina , Dinoprosta/análogos & derivados , Dinoprosta/sangue , Ácidos Docosa-Hexaenoicos/farmacologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , F2-Isoprostanos/urina , Ácidos Graxos/sangue , Feminino , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos de Membrana/sangue , Pessoa de Meia-Idade , Fosfolipídeos/sangue , Agregação Plaquetária/efeitos dos fármacos , Pós-Menopausa , Tromboxano B2/análogos & derivados , Tromboxano B2/sangue , Tromboxano B2/urina , alfa-Tocoferol/sangue
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