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1.
Arch Insect Biochem Physiol ; 103(1): e21622, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31583765

RESUMO

Eicosanoids, a group of C20 oxygenated polyunsaturated fatty acids (PUFAs), mediate various physiological processes, such as immunity, reproduction, excretion, and metabolism in insects. Arachidonic acid (AA) is used for the main precursor for the production of various eicosanoids. However, most terrestrial insects possess relatively low AA levels. Insects are presumed to be evolved since the Paleozoic era, at which oxygen levels might be much higher than current conditions. Compared with other animals, they exhibit relatively high metabolic rates with the well-developed tracheal system, which directly supply enough oxygen to active tissues like flight muscles. This might allow insects to be susceptible to reactive oxygen species (ROS) generated from high oxidative catabolism. Long-chain PUFAs including AA is usually reacted with ROS and become peroxidized. Peroxidized PUFAs cause various cellular damage. Thus, we propose a hypothesis that terrestrial insects minimize AA levels to minimize oxidative stress.


Assuntos
Ácidos Graxos Insaturados/metabolismo , Insetos/metabolismo , Estresse Oxidativo , Animais , Ácido Araquidônico/metabolismo , Metabolismo Basal , Espécies Reativas de Oxigênio/metabolismo , Fenômenos Fisiológicos Respiratórios
2.
Int Heart J ; 60(6): 1334-1343, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31735788

RESUMO

The aim of this study was to examine the impact of the serum eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio on recurrence after catheter ablation (CA) for atrial fibrillation (AF).A total of 192 patients who underwent first-time radiofrequency CA for AF were enrolled in this study. They were divided into two groups based on the median serum EPA/AA ratio before CA: a LOW group (< 0.30; n = 96) and a HIGH group (≥ 0.30; n = 96). Patients in the LOW group were younger and had smaller left atrial diameter (LAD) than those in the HIGH group. Although pulmonary vein triggers initiating AF were more frequently observed in the LOW group than the HIGH group (63% versus 46%, respectively; P = 0.021), no significant between-group difference was observed regarding the incidence of AF recurrence since the last procedure (17% versus 17%, P = 0.78; median follow-up, 37 months). Multivariate Cox regression analysis after adjustment for age and LAD revealed that EPA/AA of < 0.30 was not a significant predictor of AF recurrence (hazard ratio, 1.12; 95% confidence interval 0.53-2.37; P = 0.76). However, in the non-paroxysmal AF subgroup (n = 65), the incidence of AF recurrence was significantly higher in the LOW group than in the HIGH group (25.7% versus 6.7%, respectively; P = 0.031).In conclusion, a lower preprocedural EPA/AA ratio, which was associated with younger age and small left atrium, was not a predictor for the risk of AF recurrence after CA for AF. The potential impact of the ratio on recurrence in non-paroxysmal AF subgroups should be examined with larger samples.


Assuntos
Ácido Araquidônico/sangue , Fibrilação Atrial/sangue , Fibrilação Atrial/terapia , Ablação por Cateter , Ácido Eicosapentaenoico/sangue , Idoso , Fibrilação Atrial/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
3.
Clin Biochem ; 74: 54-59, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31669512

RESUMO

BACKGROUND: In order to manage risks of bleeding and thrombosis after some surgical procedures, platelet function is often measured repeatedly over days or weeks using laboratory tests of platelet function. To interpret test results in the perioperative period, it is necessary to understand analytical, biological and between-person variation. METHODS: We collected three separate blood specimens from 16 healthy volunteers on the first study day, and one additional specimen from each volunteer 1, 2, and 3 months later. Arachidonic acid-induced and adenosine diphosphate (ADP)-induced platelet function were measured in duplicate by whole blood impedance aggregometry using Multiplate (ASPI/ADP tests) and VerifyNow (Aspirin Reaction Units [ARU] and P2Y12 Reaction Units [PRU]). The analytical variation (CVA), within-subject variation (CVI), between-subject variation (CVG), index of individuality (II), and reference change values (RCV) were calculated. RESULTS: VerifyNow ARU demonstrated the smallest short-term and long-term variability (CVA, CVI, and CVG ~1%), resulting in short- and long-term RCV values <5%. II was also higher (1.92) for VerifyNow ARU than other platelet function tests. Multiplate ASPI and ADP tests had the highest RCV both short-(19.0% and 25.2%, respectively) and long-term (32.1% and 39.6%, respectively) due to increased CVA (>5%) and CVI (3.9-13.1%). VerifyNow PRU had a lower RCV than Multiplate ADP; but was the only test with II <0.6. CONCLUSIONS: VerifyNow ARU results can be interpreted relative to a fixed cut-off or population-based reference interval; or relative to small changes in an individual's previous values. VerifyNow PRU and Multiplate ASPI and ADP tests should only be interpreted based upon relative change; and can only distinguish relatively large (>23%) changes over several weeks.


Assuntos
Variação Biológica da População/fisiologia , Testes de Função Plaquetária , Difosfato de Adenosina/farmacologia , Ácido Araquidônico/farmacologia , Aspirina/farmacologia , Feminino , Seguimentos , Hemorragia/prevenção & controle , Humanos , Masculino , Distribuição Normal , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/farmacologia , Valores de Referência , Trombose/prevenção & controle
4.
Se Pu ; 37(8): 897-903, 2019 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-31642261

RESUMO

The global increase in the prevalence of gestational diabetes mellitus(GDM)in recent years has prompted the study of the effect of GDM on the metabolism between mother and fetus. In this study, the metabolomic investigation of the umbilical cord blood of mothers presenting GDM was performed using liquid chromatography-mass spectrometry (LC-MS), orthogonal projections to latent structures discriminant analysis (OPLS-DA), and network analysis to assess GDM-related metabolic biomarkers. The results showed that arachidonic acid (AA) played an important role in the key metabolic network while further pathway analysis suggested that GDM induced unsaturated fatty acid metabolic disorder. This study provides the underlying metabolic mechanism of GDM-induced metabolic abnormalities between mother and fetus.


Assuntos
Diabetes Gestacional/metabolismo , Sangue Fetal/metabolismo , Metabolômica , Ácido Araquidônico , Biomarcadores/sangue , Cromatografia Líquida , Feminino , Humanos , Espectrometria de Massas , Gravidez
5.
Adv Exp Med Biol ; 1161: 89-100, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31562624

RESUMO

The importance of prostaglandin E2 in cancer progression is well established, but research on its role in cancer has so far mostly been focused on epithelial cancer in adults while the knowledge about the contribution of prostaglandin E2 to childhood malignancies is limited. Neuroblastoma, an extracranial solid tumor of the sympathetic nervous system, mainly affects young children. Patients with tumors classified as high-risk have poor survival despite receiving intensive treatment, illustrating a need for new treatments complimenting existing ones. The basis of neuroblastoma treatment e.g. chemotherapy and radiation therapy, target the proliferating genetically unstable tumor cells leading to treatment resistance and relapses. The tumor microenvironment is an avenue, still to a great extent, unexplored and lacking effective targeted therapies. Cancer-associated fibroblasts is the main source of prostaglandin E2 in neuroblastoma contributing to angiogenesis, immunosuppression and tumor growth. Prostaglandin E2 is formed from its precursor arachidonic acid in a two-step enzymatic reaction. Arachidonic acid is first converted by cyclooxygenases into prostaglandin H2 and then further converted by microsomal prostaglandin E synthase-1 into prostaglandin E2. We believe targeting of microsomal prostaglandin E synthase-1 in cancer-associated fibroblasts will be an effective future therapeutic strategy in fighting neuroblastoma.


Assuntos
Dinoprostona , Neuroblastoma , Prostaglandina-E Sintases , Prostaglandina-Endoperóxido Sintases , Antineoplásicos/uso terapêutico , Ácido Araquidônico/metabolismo , Inibidores Enzimáticos/uso terapêutico , Humanos , Neuroblastoma/tratamento farmacológico , Neuroblastoma/enzimologia , Neuroblastoma/fisiopatologia , Prostaglandina-E Sintases/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Microambiente Tumoral
6.
Anal Bioanal Chem ; 411(27): 7105-7113, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31515585

RESUMO

A novel electrochemical approach for determination of arachidonic acid (ARA) was developed based on the linear arginine-glycine-aspartic-Au (RGD-Au) nanomaterial modified on glassy carbon electrode (GCE). The prepared material was characterized by transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), ultraviolet-visible spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The electrochemical signal was obtained from the reduction of 1,4-naphthoquinone and ARA served as a proton source. Under the optimum experimental conditions, the RGD-Au-based electrode was used to analyze ARA. Meanwhile, the electrochemical characteristics were also studied by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and linear sweep voltammetry (LSV). The sensor showed a wider linear range from 0.5 to 100 µM and the linear fitting equation was Ip (µA) = 0.0721 c + 2.4583 (R2 = 0.9987) with a detection limit of 80 nM. The application of the sensor in real samples was tested and compared with that of LC-MS/MS. This sensor would be a promising platform for detection of ARA in blood plasma. Graphical abstract.


Assuntos
Ácido Araquidônico/análise , Arginina/química , Ácido Aspártico/química , Glicina/química , Ouro/química , Nanopartículas/química , Ácido Araquidônico/sangue , Técnicas Eletroquímicas/métodos , Eletrólitos/química , Humanos , Limite de Detecção , Reprodutibilidade dos Testes , Análise Espectral/métodos
7.
BMC Vet Res ; 15(1): 324, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492181

RESUMO

BACKGROUND: Obesity in cats has been associated with alterations in adipokines including: adiponectin, interleukin-6 (IL6), and tumor necrosis factor-α (TNFα). Omega-3 polyunsaturated fatty acids have multiple beneficial effects on obesity-associated disorders, and therefore may alleviate these alterations. This study aimed to determine the effects of body condition, fat depot, troglitazone, and different fatty acids on secretion of adiponectin, IL6 and TNFα from adipose tissue of healthy cats. Subcutaneous and visceral adipose tissue samples were collected from 18 healthy intact female cats, and body condition score (Range 3-7/9) was determined. Concentrations of adiponectin were measured in mature adipocytes cultures and concentrations of IL6 and TNFα were measured in stromovascular cells cultures following treatment with control medium, troglitazone at 10 µM, eicosapentaenoic acid, arachidonic acid, or palmitic acid, at 25, 50, or 100 µM. RESULTS: Stromovascular cells of visceral origin secreted higher concentrations of IL6 than corresponding cells of subcutaneous origin (P = 0.003). Arachidonic acid treatment at 25, 50, and 100 µM increased IL6 secretion in subcutaneous (P = 0.045, P = 0.002, and P < 0.001, respectively) and visceral (P = 0.034, P = 0.001, and P < 0.001, respectively) stromovascular cells. Eicosapentaenoic acid treatment increased TNFα secretion in subcutaneous stromovascular cells at 25, 50, and 100 µM (P = 0.002, P = 0.001, and P = 0.015, respectively) and in visceral stromovascular cells at 50 µM (P < 0.001). No significant effect on medium adiponectin concentration was observed following troglitazone treatment (P = 0.4) or fatty acids treatments at 25 (P = 0.2), 50 (P = 0.8), or 100 (P = 0.7) µM. Body condition score did not have significant effects on medium concentrations of adiponectin (P = 0.4), IL6 (P = 0.1), or TNFα (P = 0.8). CONCLUSIONS: This study demonstrated higher basal secretion of IL6 from visceral compared to subcutaneous adipose tissue, a stimulatory effect of arachidonic acid on secretion of IL6 and a stimulatory effect of eicosapentaenoic acid on TNFα from feline adipose tissue.


Assuntos
Adipocinas/metabolismo , Tecido Adiposo/efeitos dos fármacos , Gorduras na Dieta/farmacologia , Ácidos Graxos/farmacologia , Tecido Adiposo/metabolismo , Animais , Ácido Araquidônico/metabolismo , Constituição Corporal , Gatos , Células Cultivadas , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/metabolismo , Feminino , Interleucina-6/metabolismo , Ácido Palmítico/metabolismo , Troglitazona/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
8.
J Agric Food Chem ; 67(35): 9851-9857, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31418561

RESUMO

Arachidonic acid (ARA, C20:4) is a typical ω-6 polyunsaturated fatty acid with special functions. Using Yarrowia lipolytica as an unconventional chassis, we previously showed the performance of the Δ-6 pathway in ARA production. However, a significant increase in the Δ-9 pathway has rarely been reported. Herein, the Δ-9 pathway from Isochrysis galbana was constructed via pathway engineering, allowing us to synthesize ARA at 91.5 mg L-1. To further improve the ARA titer, novel enzyme fusions of Δ-9 elongase and Δ-8 desaturase were redesigned in special combinations containing different linkers. Finally, with the integrated pathway engineering and synthetic enzyme fusion, a 29% increase in the ARA titer, up to 118.1 mg/L, was achieved using the reconstructed strain RH-4 that harbors the rigid linker (GGGGS). The results show that the combined pathway and protein engineering can significantly facilitate applications of Y. lipolytica.


Assuntos
Ácido Araquidônico/biossíntese , Engenharia Metabólica , Yarrowia/genética , Yarrowia/metabolismo , Acetiltransferases/genética , Acetiltransferases/metabolismo , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Glucose/metabolismo , Haptófitas/enzimologia
9.
Nutrients ; 11(7)2019 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-31284588

RESUMO

Evidence suggests a role of long chain polyunsaturated fatty acids (LC-PUFA), in which animal foods are especially rich, in optimal neural development. The LC-PUFAs docosahexaenoic acid (DHA) and arachidonic acid, found in high concentrations in the brain and retina, have potential beneficial effects on cognition, and motor and visual functions. Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism. The treatment of PKU consists of a phenylalanine-free diet, which limits the intake of natural proteins of high biological value. In this systematic review, we summarize the available evidence supporting a role for LC-PUFA supplementation as an effective means of increasing LC-PUFA levels and improving visual and neurocognitive functions in PKU patients. Data from controlled trials of children and adults (up to 47 years of age) were obtained by searching the MEDLINE and SCOPUS databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. For each selected study, the risk of bias was assessed applying the methodology of the Cochrane Collaboration. The findings indicate that DHA supplementation in PKU patients from 2 weeks to 47 years of age improves DHA status and decreases visual evoked potential P100 wave latency in PKU children from 1 to 11 years old. Neurocognitive data are inconclusive.


Assuntos
Ácido Araquidônico/administração & dosagem , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Fenilcetonúrias/dietoterapia , Adolescente , Adulto , Ácido Araquidônico/efeitos adversos , Criança , Pré-Escolar , Cognição , Dieta com Restrição de Proteínas , Suplementos Nutricionais/efeitos adversos , Ácidos Docosa-Hexaenoicos/efeitos adversos , Potencial Evocado Motor , Potenciais Evocados Visuais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Fenilcetonúrias/diagnóstico , Fenilcetonúrias/fisiopatologia , Fenilcetonúrias/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto Jovem
10.
Nat Rev Neurol ; 15(8): 459-472, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31263255

RESUMO

Epilepsy is a chronic neurological disease characterized by an enduring propensity for generation of seizures. The pathogenic processes of seizure generation and recurrence are the subject of intensive preclinical and clinical investigations as their identification would enable development of novel treatments that prevent epileptic seizures and reduce seizure burden. Such treatments are particularly needed for pharmacoresistant epilepsies, which affect ~30% of patients. Neuroinflammation is commonly activated in epileptogenic brain regions in humans and is clearly involved in animal models of epilepsy. An increased understanding of neuroinflammatory mechanisms in epilepsy has identified cellular and molecular targets for new mechanistic therapies or existing anti-inflammatory drugs that could overcome the limitations of current medications, which provide only symptomatic control of seizures. Moreover, inflammatory mediators in the blood and molecular imaging of neuroinflammation could provide diagnostic, prognostic and predictive biomarkers for epilepsy, which will be instrumental for patient stratification in future clinical studies. In this Review, we focus on our understanding of the IL-1 receptor-Toll-like receptor 4 axis, the arachidonic acid-prostaglandin cascade, oxidative stress and transforming growth factor-ß signalling associated with blood-brain barrier dysfunction, all of which are pathways that are activated in pharmacoresistant epilepsy in humans and that can be modulated in animal models to produce therapeutic effects on seizures, neuronal cell loss and neurological comorbidities.


Assuntos
Encefalite/diagnóstico , Encefalite/metabolismo , Epilepsia/diagnóstico , Epilepsia/terapia , Animais , Ácido Araquidônico/metabolismo , Biomarcadores/sangue , Encefalite/complicações , Epilepsia/complicações , Epilepsia/metabolismo , Humanos , Estresse Oxidativo , Prostaglandinas/metabolismo , Receptores de Interleucina-1/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Fator de Crescimento Transformador beta/metabolismo
11.
Biomed Khim ; 65(3): 245-250, 2019 Apr.
Artigo em Russo | MEDLINE | ID: mdl-31258149

RESUMO

The content of vasoactive compounds and arachidonic acid in the placenta and amniotic fluid was studied in full-term (39-40 weeks) physiological pregnancy and preeclampsia (PE). The content of metabolites of nitric oxide (NOx), endothelin-1, thromboxane B2 (TxB2), prostacycline (PGI2) and arachidonic acid was estimated using spectrophotometric, immunoenzyme methods and gas-liquid chromatography. It was found that in PE the content of vasoconstrictors, of endothelin and TxB2, increased in the placenta and amniotic fluid, while the content of vasodilators, PGI2 and NOx decreased. Despite the same directionality of changes in both studied objects, the degree of changes differed and was more pronounced in the placenta. A direct or inverse correlative relationship was found between various vasoactive components (depending on their effect on vascular tone). In the case of arachidonic acid changes in its content in PE correlated with the level of vasoactive compounds, the source of which it is. The revealed differences in the ratio of vasoactive components obviously play a pathogenetic role in the development of PE and its subsequent complications.


Assuntos
Líquido Amniótico/química , Ácido Araquidônico/análise , Placenta/química , Pré-Eclâmpsia , Endotelina-1/análise , Feminino , Humanos , Óxido Nítrico/análise , Gravidez , Prostaglandinas I/análise , Tromboxano B2/análise
12.
Insect Biochem Mol Biol ; 111: 103179, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31255640

RESUMO

Eicosanoids play crucial roles in mediating insect immune responses. In vertebrates, phospholipase A2 (PLA2) releases arachidonic acid (AA) from phospholipids (PLs) for biosynthesis of various eicosanoids. However, little AA is found in PLs of lepidopteran insects. Spodoptera exigua, a lepidopteran insect, is known to use eicosanoids to mediate immunity. Although AA was not detected in PLs of hemocytes and fat body (two immune tissues) of naïve larvae, it was detected at small but significant level after bacterial infection, suggesting induction of AA biosynthesis for immunity. Based on a mammalian AA biosynthetic pathway, this study hypothesizes that AA is synthesized from C18 polyunsaturated fatty acid (PUFA) precursor by subsequent desaturation and elongation reactions because PLs of S. exigua larvae are rich in linoleic acid. After inhibiting PLA2 activity to prevent release of free fatty acids, different PUFA precursors were injected to S. exigua larvae followed by assessment of eicosanoid-mediated cellular immune response. ω-6 PUFAs were effective in inducing immune response whereas α-linolenic acid (an ω-3 PUFA) was not. Several fatty acyl desaturases (SeDESs) have been predicted from S. exigua transcriptomes. Specific inhibitors against Δ5 or Δ6 DESs inhibited eicosanoid-mediated immune responses. Furthermore, RNA interference (RNAi) specific to Δ5 or Δ6 DES genes significantly suppressed eicosanoid-mediated immune responses. Four very long chain fatty acid elongase genes (SeEloV-A ∼ SeEloV-D) were predicted. Among respective RNAi treatments of these genes, only one RNAi treatment specific to type 5 elongase (SeEloV-B) suppressed eicosanoid-mediated immune response. These results suggest that S. exigua larvae can synthesize AA from linoleic acid via Δ5- and Δ6-desaturations by SeDESs along with chain elongation by SeEloV-B. Finally, this study showed significant fitness cost of uncontrolled AA biosynthesis. AA injection alone without bacterial challenge significantly induced both cellular and humoral immune responses. This unnecessary energy expense due to free AA resulted in reduced pupal size and decreased adult egg production. The detrimental effect of free AA explains physiological significance of little AA content in lepidopteran insects except for life-or-death situation such as pathogen infection.


Assuntos
Ácido Araquidônico/biossíntese , Spodoptera/metabolismo , Animais , Vias Biossintéticas , Eicosanoides/metabolismo , Escherichia coli , Ácidos Graxos Insaturados/metabolismo , Larva/genética , Larva/imunologia , Larva/metabolismo , Larva/microbiologia , Interferência de RNA , Spodoptera/genética , Spodoptera/imunologia , Spodoptera/microbiologia
13.
Inflammopharmacology ; 27(5): 903-910, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31359235

RESUMO

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain and inflammatory conditions such as arthritis. However, both arthritis and many NSAIDs increase cardiovascular (CV) risks. The dose-dependency of the elevated CV risks of NSAIDs has not been well-studied. We tested the hypothesis that low but still effective doses of these drugs are void of CV side effects. As the model drug, we chose diclofenac because of its known high CV toxicity, as markers of CV risks, we assessed concentrations of cytochrome P450-mediated metabolites of arachidonic acid (ArA), and we used adjuvant arthritis as an experimental model of arthritis. Following 7 daily doses (2.5-15 mg/kg), the effective dosage range of diclofenac was identified (> 5 mg/kg/day). While 7 consecutive days of low therapeutic doses did not alter the CYP-mediated ArA metabolism, the highest dose of 15 mg/kg/day caused imbalances in ArA metabolic profiles toward cardiotoxicity by increasing the ratio of cardiotoxic 20-hydroxyeicosatetraenoic acid over cardioprotective epoxyeicosatrienoic acids. This is suggestive of dose-dependency of NSAID cardiotoxicity, and that low therapeutic doses may be void of CV side effects. Human studies are needed to examine the safety of low but effective doses of NSAIDs.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Artrite Experimental/tratamento farmacológico , Doenças Cardiovasculares/induzido quimicamente , Animais , Ácido Araquidônico/metabolismo , Artrite Experimental/metabolismo , Diclofenaco/administração & dosagem , Diclofenaco/efeitos adversos , Ácidos Hidroxieicosatetraenoicos/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Risco
14.
Int J Mol Sci ; 20(15)2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31357612

RESUMO

As a major component of cell membrane lipids, Arachidonic acid (AA), being a major component of the cell membrane lipid content, is mainly metabolized by three kinds of enzymes: cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450) enzymes. Based on these three metabolic pathways, AA could be converted into various metabolites that trigger different inflammatory responses. In the kidney, prostaglandins (PG), thromboxane (Tx), leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs) are the major metabolites generated from AA. An increased level of prostaglandins (PGs), TxA2 and leukotriene B4 (LTB4) results in inflammatory damage to the kidney. Moreover, the LTB4-leukotriene B4 receptor 1 (BLT1) axis participates in the acute kidney injury via mediating the recruitment of renal neutrophils. In addition, AA can regulate renal ion transport through 19-hydroxystilbenetetraenoic acid (19-HETE) and 20-HETE, both of which are produced by cytochrome P450 monooxygenase. Epoxyeicosatrienoic acids (EETs) generated by the CYP450 enzyme also plays a paramount role in the kidney damage during the inflammation process. For example, 14 and 15-EET mitigated ischemia/reperfusion-caused renal tubular epithelial cell damage. Many drug candidates that target the AA metabolism pathways are being developed to treat kidney inflammation. These observations support an extraordinary interest in a wide range of studies on drug interventions aiming to control AA metabolism and kidney inflammation.


Assuntos
Ácido Araquidônico/metabolismo , Metabolismo dos Lipídeos , Nefrite/etiologia , Nefrite/metabolismo , Animais , Biomarcadores , Suscetibilidade a Doenças , Humanos , Redes e Vias Metabólicas/efeitos dos fármacos , Terapia de Alvo Molecular , Nefrite/tratamento farmacológico , Nefrite/patologia , Transdução de Sinais/efeitos dos fármacos
15.
Nutrients ; 11(6)2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31181624

RESUMO

BACKGROUND: People living with human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) (PLWH) are at an increased risk of cardiovascular disease. Diet-related factors may contribute. The aim of this pilot study was to determine, in PLWH, the relationship between atherosclerosis assessed by carotid intima-media thickness (CIMT) and (A) plasma antioxidant micronutrients and oxidative stress or (B) red blood cell polyunsaturated fatty acids (RBC PUFA), particularly long chain omega-3 polyunsaturated fatty acids (n-3 PUFA). METHODS: (A) In a cross-sectional study, subjects had CIMT evaluated by high resolution carotid artery ultrasound. Plasma was collected for vitamin C, measured by spectrophotometry; and alpha- and gamma-tocopherol, retinol, and malondialdehyde-a marker of oxidative stress-using high pressure liquid chromatography and fluorescence spectrophotometry. (B) In a prospective cohort study, other subjects had RBC PUFA measured at baseline, using gas chromatography, and CIMT assessed at baseline and repeated after 2 years. Clinical data was also collected. RESULTS: (A) 91 PLWH participated. Only alpha- and gamma-tocopherol levels were positively correlated with CIMT. In a multivariate analysis, age and systolic blood pressure were significantly associated with CIMT with gamma-tocopherol near significance (p = 0.053). (B) 69 PLWH participated. At baseline, docosahexaenoic acid (n-3 PUFA) and the ratio of docosahexaenoic acid to arachidonic acid (n-6 PUFA) were significantly and negatively correlated with CIMT. However, a multivariate analysis failed to detect a significant relationship either at baseline or 2 years after. CONCLUSION: In addition to age and systolic blood pressure, atherosclerosis assessed by CIMT might be associated with higher serum gamma-tocopherol levels. There was a non-significant association between CIMT and RBC n-3 PUFA or the ratio of n-3 to n-6 PUFA.


Assuntos
Antioxidantes/metabolismo , Aterosclerose/etiologia , Eritrócitos/metabolismo , Ácidos Graxos Insaturados/sangue , Infecções por HIV/complicações , Estresse Oxidativo , gama-Tocoferol/sangue , Adulto , Ácido Araquidônico/sangue , Aterosclerose/sangue , Aterosclerose/patologia , Pressão Sanguínea , Espessura Intima-Media Carotídea , Estudos Transversais , Ácidos Docosa-Hexaenoicos/sangue , Feminino , Infecções por HIV/sangue , Infecções por HIV/patologia , Humanos , Masculino , Malondialdeído/sangue , Micronutrientes/sangue , Pessoa de Meia-Idade , Análise Multivariada , Projetos Piloto , Estudos Prospectivos , alfa-Tocoferol/sangue
16.
Methods Mol Biol ; 1982: 75-101, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31172467

RESUMO

The NADPH oxidase NOX2 complex consists of assembled cytosolic and redox membrane proteins. In mammalian cells, natural arachidonic acid (cis-AA), released by activated phospholipase-A2, plays an important role in the activation of the NADPH oxidase, but the mechanism of action of cis-AA is still a matter of debate. In cell-free systems, cis-AA is commonly used for activation although its structural effects are still unclear. Undoubtedly cis-AA participates in the synergistic multi-partner assembly that can be hardly studied at the molecular level in vivo due to cellular complexity. The capacity of this anionic amphiphilic fatty acid to activate the oxidase is mainly explained by its ability to disrupt intramolecular bonds, mimicking phosphorylation events in cell signaling and therefore allowing protein-protein interactions. Interestingly the geometric isomerism of the fatty acid and its purity are crucial for optimal superoxide production in cell-free assays. Indeed, optimal NADPH oxidase assembly was hampered by the substitution of the cis form by the trans forms of AA isomers (Souabni et al., BBA-Biomembranes 1818:2314-2324, 2012). Structural analysis of the changes induced by these two compounds, by circular dichroism and by biochemical methods, revealed differences in the interaction between subunits. We describe how the specific geometry of AA plays an important role in the activation of the NOX2 complex.


Assuntos
Ácido Araquidônico/metabolismo , NADPH Oxidases/metabolismo , Fagócitos/enzimologia , Ácido Araquidônico/química , Fracionamento Celular , Membrana Celular/enzimologia , Membrana Celular/metabolismo , Sistema Livre de Células , Colorimetria , Ativação Enzimática , Isomerismo , Estrutura Molecular , NADPH Oxidases/antagonistas & inibidores , NADPH Oxidases/química , NADPH Oxidases/isolamento & purificação , Neutrófilos/enzimologia , Fagócitos/imunologia , Proteínas Recombinantes de Fusão , Análise Espectral
17.
Environ Sci Pollut Res Int ; 26(22): 22197-22208, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31148000

RESUMO

Acrylamide (ACR), a ubiquitous agent, has various chemical and industrial applications, and it is found in backed or fried carbohydrate-rich food. It has been related to multiple toxicological effects, and it causes high cytotoxicity through oxidative stress. The present study aimed to investigate the potential effect of ACR toxicity administered at different concentrations (5, 10, and 20 mg/L), during 5 days, in order to evaluate the fatty acid (FA) composition and redox state in the digestive gland of Mactra corallina. The results showed, in ACR-treated clams, a significant increase in malondialdehyde, hydrogen peroxide, protein carbonyl, and metallothionein levels, as well as an alteration of the enzymatic (superoxide dismutase, glutathione peroxidase, and catalase) and non-enzymatic (reduced glutathione and ascorbic acid) antioxidant status. However, acetylcholinesterase activity was inhibited in a concentration-dependent manner. In our experiment, the n-3 (Omega-3) and n-6 (Omega-6) polyunsaturated fatty acid levels were significantly changed in all ACR-treated groups. A decrease in eicosapentaenoic acid (C20:5n-3, EPA) and docosahexaenoic acid (C22:6n-3, DHA) was observed in 10-mg/L and 20-mg/L ACR-treated groups. Nevertheless, arachidonic acid (C20:4n-6, ARA) and its precursor linoleic acid (C18:2n-6, LA) were increased. Besides oxidative stress parameters, FA composition may be an additional tool for assessing ACR contamination.


Assuntos
Acrilamida/farmacologia , Bivalves/metabolismo , Digestão/efeitos dos fármacos , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos/metabolismo , Superóxido Dismutase/metabolismo , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Ácido Araquidônico/química , Bivalves/química , Catalase/metabolismo , Ácidos Docosa-Hexaenoicos/química , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/química , Glutationa/metabolismo , Ácido Linoleico/química , Ácido Linoleico/farmacologia , Oxirredução , Estresse Oxidativo/efeitos dos fármacos
18.
Anim Sci J ; 90(8): 999-1007, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31148331

RESUMO

Bovine mastitis is one of the most prevalent and costly diseases in the dairy industry. Lipid mediators are signaling molecules which coordinately and intricately modulate inflammation. They are produced from polyunsaturated fatty acids (PUFAs) in the cellular membrane via several enzymes including cyclooxygenase (COX) and lipoxygenase (LOX). In the present study, we performed comprehensive analysis of lipid production in milk obtained from clinical or subclinical mastitic cows using liquid chromatography/mass spectrometry. We detected 26, 24, and 40 kinds of lipid constantly in healthy, subclinical, and clinical mastitic milk, respectively. In clinical mastitic milk, the amount of a major n-6 PUFA, arachidonic acid (AA), tended to increase, whereas amounts of major n-3 PUFAs, eicosapentaenoic acid and docosahexaenoic acid, tended to decrease. The amounts of several AA-derived lipids including COX-catalyzed prostaglandin (PG) D2 and PGE2 , and LOX-catalyzed leukotriene (LT) B4 were increased in clinical mastitic milk. Although subclinical mastitic milk represented similar trend of lipid production to healthy milk, amounts of several lipids such as LTD4 , 14,15-dihydroxyeicosatrienoic acid, and 14-epoxyeicosatrienoic acid changed. These findings would be helpful for better understanding of mastitis pathology and give us some insights to develop a new diagnostic and therapeutic strategy.


Assuntos
Mastite Bovina/metabolismo , Leite/metabolismo , Animais , Ácido Araquidônico/metabolismo , Biomarcadores/metabolismo , Bovinos , Dinoprostona/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Ácidos Graxos Insaturados/metabolismo , Feminino , Leucotrieno B4/metabolismo , Lipoxigenase/metabolismo , Mastite Bovina/diagnóstico , Mastite Bovina/etiologia , Prostaglandina D2/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo
19.
Nat Commun ; 10(1): 2602, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31197136

RESUMO

Temperature is a key factor for determining the lifespan of both poikilotherms and homeotherms. It is believed that animals live longer at lower body temperatures. However, the precise mechanism remains largely unknown. Here, we report that autophagy serves as a boost mechanism for longevity at low temperature in the nematode Caenorhabditis elegans. The adiponectin receptor AdipoR2 homolog PAQR-2 signaling detects temperature drop and augments the biosynthesis of two ω-6 polyunsaturated fatty acids, γ-linolenic acid and arachidonic acid. These two polyunsaturated fatty acids in turn initiate autophagy in the epidermis, delaying an age-dependent decline in collagen contents, and extending the lifespan. Our findings reveal that the adiponectin receptor PAQR-2 signaling acts as a regulator linking low temperature with autophagy to extend lifespan, and suggest that such a mechanism may be evolutionally conserved among diverse organisms.


Assuntos
Autofagia/fisiologia , Proteínas de Caenorhabditis elegans/fisiologia , Caenorhabditis elegans/fisiologia , Longevidade/fisiologia , Proteínas de Membrana/fisiologia , Animais , Animais Geneticamente Modificados , Ácido Araquidônico/biossíntese , Temperatura Baixa , Colágeno/metabolismo , Epiderme/metabolismo , Ácidos Graxos Ômega-6/biossíntese , Interferência de RNA , Transdução de Sinais/fisiologia
20.
Biochemistry (Mosc) ; 84(2): 164-170, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31216975

RESUMO

Quantitative and qualitative assessments of cell membrane components are essential for the accurate interpretation of processes occurring in biological membranes. Changes in the structure and function of cell membrane components have been linked to oxidative stress. Oxidative stress induced by chronic ethanol consumption or cancer transformation has been implicated in changing the levels of phospholipids and fatty acids in the cell membrane. In this study, we used high-performance liquid chromatography to quantitate the effects of alcohol and malignant transformation on membrane components, namely phospholipids and free fatty acids. Ethanol increased the phospholipid levels. Moreover, the process of malignant transformation was accompanied by increased levels of phospholipids and arachidonic acid as well as decreased levels of linoleic acid and α-linolenic acid. Thus, these oxidative stress-inducing conditions that cause variations in the cellular composition affect the actions of the cell membrane and cell function.


Assuntos
Membrana Celular/metabolismo , Fosfolipídeos/metabolismo , Administração Oral , Intoxicação Alcoólica/tratamento farmacológico , Animais , Ácido Araquidônico/química , Ácido Araquidônico/isolamento & purificação , Ácido Araquidônico/metabolismo , Etanol/administração & dosagem , Etanol/toxicidade , Masculino , Estresse Oxidativo , Fosfolipídeos/química , Fosfolipídeos/isolamento & purificação , Ratos , Ratos Wistar
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