RESUMO
The efficacy of n-3 polyunsaturated fatty acids (PUFAs) in improving outcomes in a renal ischemia-reperfusion injury (IRI) model has previously been reported. However, the underlying mechanisms remain poorly understood and few reports demonstrate how dietary n-3 PUFAs influence the composition of membrane phospholipids in the kidney. Additionally, it has not been elucidated whether perilla oil (PO), which is mainly composed of the n-3 alpha-linolenic acid, mitigates renal IRI. In this study, we investigated the effect of dietary n-3 PUFAs (PO), compared with an n-6 PUFA-rich soybean oil (SO) diet, on IRI-induced renal insufficiency in a rat model. Levels of membrane phospholipids containing n-3 PUFAs were higher in the kidney of PO-rich diet-fed rats than the SO-rich diet-fed rats. Levels of blood urea nitrogen and serum creatinine were significantly higher in the ischemia-reperfusion group than the sham group under both dietary conditions. However, no significant differences were observed in blood urea nitrogen, serum creatinine, or histological damage between PO-rich diet-fed rats and SO-rich diet-fed rats. In the kidney of PO-rich diet-fed rats, levels of arachidonic acid and arachidonic acid-derived pro-inflammatory lipid mediators were lower than SO-rich diet-fed rats. Eicosapentaenoic acid and eicosapentaenoic acid-derived lipid mediators were significantly higher in the kidney of PO-rich than SO-rich diet-fed rats. These results suggest that dietary n-3 PUFAs alter the fatty acid composition of membrane phospholipids and lipid mediators in the kidney; however, this does not attenuate renal insufficiency or histological damage in a renal IRI model.
Assuntos
Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/metabolismo , Insuficiência Renal/dietoterapia , Traumatismo por Reperfusão/dietoterapia , Óleo de Soja/metabolismo , Animais , Ácido Araquidônico/metabolismo , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-6/administração & dosagem , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Fosfolipídeos/metabolismo , Óleos de Plantas/química , Ratos , Ratos Sprague-Dawley , Insuficiência Renal/metabolismo , Insuficiência Renal/patologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Óleo de Soja/administração & dosagem , Óleo de Soja/química , Falha de Tratamento , Ácido alfa-Linolênico/químicaRESUMO
Diabetic retinopathy (DR) is a widespread vision-threatening disease, and neuroretinal abnormality should be considered as an important problem. Brain-derived neurotrophic factor (BDNF) has recently been considered as a possible treatment to prevent DR-induced neuroretinal damage, but how BDNF is upregulated in DR remains unclear. We found an increase in hydrogen peroxide (H2O2) in the vitreous of patients with DR. We confirmed that human retinal endothelial cells secreted H2O2 by high glucose, and H2O2 reduced cell viability of MIO-M1, Müller glia cell line, PC12D, and the neuronal cell line and lowered BDNF expression in MIO-M1, whereas BDNF administration recovered PC12D cell viability. Streptozocin-induced diabetic rats showed reduced BDNF, which is mainly expressed in the Müller glia cell. Oral intake of eicosapentaenoic acid ethyl ester (EPA-E) ameliorated BDNF reduction and oscillatory potentials (OPs) in electroretinography (ERG) in DR. Mass spectrometry revealed an increase in several EPA metabolites in the eyes of EPA-E-fed rats. In particular, an EPA metabolite, 18-hydroxyeicosapentaenoic acid (18-HEPE), induced BDNF upregulation in Müller glia cells and recovery of OPs in ERG. Our results indicated diabetes-induced oxidative stress attenuates neuroretinal function, but oral EPA-E intake prevents retinal neurodegeneration via BDNF in Müller glia cells by increasing 18-HEPE in the early stages of DR.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/farmacologia , Retinopatia Diabética/metabolismo , Ácido Eicosapentaenoico/farmacologia , Células Endoteliais/metabolismo , Células Ependimogliais/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Neurônios Retinianos/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Diabetes Mellitus Experimental/metabolismo , Eletrorretinografia , Células Endoteliais/efeitos dos fármacos , Células Ependimogliais/efeitos dos fármacos , Ácidos Graxos Ômega-3/farmacologia , Feminino , Humanos , Peróxido de Hidrogênio/metabolismo , Masculino , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley , Neurônios Retinianos/efeitos dos fármacosAssuntos
Dermatite Atópica/complicações , Suplementos Nutricionais , Ácido Eicosapentaenoico/administração & dosagem , Prurido/dietoterapia , Psoríase/complicações , Animais , Antígenos de Dermatophagoides/administração & dosagem , Antígenos de Dermatophagoides/imunologia , Dermatite Atópica/imunologia , Modelos Animais de Doenças , Eicosanoides/metabolismo , Humanos , Imiquimode/administração & dosagem , Imiquimode/imunologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Prurido/etiologia , Prurido/patologia , Psoríase/imunologia , Pele/efeitos dos fármacos , Pele/patologia , Resultado do TratamentoRESUMO
Allergic conjunctivitis (AC) is one of the most common ocular surface diseases in the world. In AC, T helper type 2 (Th2) immune responses play central roles in orchestrating inflammatory responses. However, the roles of lipid mediators in the onset and progression of AC remain to be fully explored. Although previous reports have shown the beneficial effects of supplementation of ω-3 fatty acids in asthma or atopic dermatitis, the underlying molecular mechanisms are poorly understood. In this study, a diet rich in ω-3 fatty acids alleviated AC symptoms in both early and late phases without affecting Th2 immune responses, but rather by altering the lipid mediator profiles. The ω-3 fatty acids completely suppressed scratching behavior toward the eyes, an allergic reaction provoked by itch. Although total serum IgE levels and the expression levels of Th2 cytokines and chemokines in the conjunctiva were not altered by ω-3 fatty acids, eosinophil infiltration into the conjunctiva was dramatically suppressed. The levels of ω-6-derived proinflammatory lipid mediators, including those with chemoattractant properties for eosinophils, were markedly reduced in the conjunctivae of ω-3 diet-fed mice. Dietary ω-3 fatty acids can alleviate a variety of symptoms of AC by altering the lipid mediator profile.-Hirakata, T., Lee, H.-C., Ohba, M., Saeki, K., Okuno, T., Murakami, A., Matsuda, A., Yokomizo, T. Dietary ω-3 fatty acids alter the lipid mediator profile and alleviate allergic conjunctivitis without modulating Th2 immune responses.