RESUMEN
Psidium brownianum Mart is reported in the literature by antinociceptive and antioxidant activities, indicating that this species' secondary metabolites might be used to control inflammatory processes. The present study aimed to characterize the topical antiedematogenic activity of the essential oil of Psidium brownianum Mart. (OEPB) in ear edema models by different inflammatory agents. Female Swiss mice (25-35â g) and Wistar albino rats (200-300â g) were used throughout tests (n=6/group) on acute or chronic edema models induced by single and multiple topical applications. The OEPB is administered topically pure or at a concentration of 100 or 200â mg/mL. The antiedematogenic mechanism of OEPB was analyzed by administering capsaicin, arachidonic acid, histamine, and phenol at the best effective dose (200â mg/mL). The results showed a significant reduction of edema-induced single (28.87 %) and multiple (50.13 %) applications of croton oil compared to the negative control group. Regarding potential mechanisms of action, OEPB (200â mg/mL) inhibited the development of edema triggered by capsaicin (29.95 %), arachidonic acid (22.66 %), phenol (23.35 %), and histamine (75.46 %), suggesting an interference with the histaminergic pathway. These results indicate that OEPB presents a topical antiedematogenic effect in acute and chronic murine models, possibly interfering with inflammatory pathways triggered by mediators such as histamine.
Asunto(s)
Aceites Volátiles , Psidium , Ratones , Femenino , Animales , Aceites Volátiles/farmacología , Aceites Volátiles/uso terapéutico , Capsaicina , Histamina/efectos adversos , Ácido Araquidónico/efectos adversos , Edema/inducido químicamente , Edema/tratamiento farmacológico , Extractos Vegetales/farmacologíaRESUMEN
Excessive fructose corn syrup (FCS) intake brings a series of health problems. The aim of the present study was to explore the mechanism of FCS-induced metabolic disorders from the perspective of gut microbiota. Mice were fed for 16 weeks with normal or 30% FCS drinking water. Compared to the control group, FCS caused significantly higher fat deposition, hepatic steatosis, liver and intestinal inflammatory damages (P<.05). FCS increased the abundance of Muribaculaceae in vivo and in vitro, which was positively correlated with the indices of metabolic disorders (P<.05). In vivo and in vitro data indicated that FCS enhanced the microbial function involved in pentose phosphate pathway and arachidonic acid metabolism, metabolomics further demonstrated that FCS led to an increase in prostaglandins (the catabolites of arachidonic acid) (P<.05). Our study confirmed that FCS can directly promote gut microbiota to synthesize inflammatory factor prostaglandins, which provides new insights and directions for the treatment of FCS-induced metabolic disorders and inflammation.
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Microbioma Gastrointestinal , Enfermedades Metabólicas , Ratones , Animales , Ácido Araquidónico/efectos adversos , Zea mays , Fructosa/efectos adversos , Obesidad/metabolismo , Grasas de la Dieta/farmacología , Prostaglandinas , Ratones Endogámicos C57BL , Dieta Alta en GrasaRESUMEN
OBJECTIVE: To investigate and reveal the underlying mechanism of the effect of total saponins from Dioscoreae nipponica Makino (TSDN) on the arachidonic acid pathway in monosodium urate (MSU) crystal-induced M1-polarized macrophages. METHODS: M1 polarization of RAW264.7 cells were induced by 1 µ g/mL lipopolysaccharide (LPS). The methylthiazolyldiphenyl-tetrazolium bromide method was then used to screen the concentration of TSDN. MSU (500 µ g/mL) was used to induce the gouty arthritis model. Afterwards, 10 µ g/L TSDN and 8 µ mol/L celecoxib, which was used as a positive control, were added to the above LPS and MSU-induced cells for 24 h. The mRNA and protein expressions of cyclooxygenase (COX) 2, 5-lipoxygenase (5-LOX), microsomal prostaglandin E synthase derived eicosanoids (mPGES)-1, leukotriene B (LTB)4, cytochrome P450 (CYP) 4A, and prostaglandin E2 (PGE2) were tested by real-time polymerase chain reaction and Western blotting, respectively. The enzyme-linked immunosorbent assay was used to test the contents of M1 markers, including inducible nitric oxid synthase (NOS) 2, CD80, and CD86. RESULTS: TSDN inhibited the proliferation of M1 macrophages and decreased both the mRNA and protein expressions of COX2, 5-LOX, CYP4A, LTB4, and PGE2 (P<0.01) while increased the mRNA and protein expression of mPGES-1 (P<0.05 or P<0.01). TSDN could also significantly decrease the contents of NOS2, CD80, and CD86 (P<0.01). CONCLUSION: TSDN has an anti-inflammation effect on gouty arthritis in an in vitro model by regulating arachidonic acid signaling pathway.
Asunto(s)
Artritis Gotosa , Dioscorea , Saponinas , Ácido Úrico/metabolismo , Ácido Araquidónico/efectos adversos , Ácido Araquidónico/metabolismo , Lipopolisacáridos , Saponinas/farmacología , Macrófagos , Transducción de Señal , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: Vertebral abnormalities in offspring of diabetic mothers make major challenges worldwide and were not sufficiently studied before. AIM: To investigate the effects of alloxan-induced diabetes on rats' lumbar vertebrae, and to assess the potential beneficial impact of arachidonic acid. MATERIALS AND METHODS: Pregnant rats were randomly equally divided into four groups: control, alloxan-induced diabetes received alloxan injection 150 mg∕kg, alloxan + arachidonic acid group received arachidonic acid 10 µg∕animal then given alloxan injection, and arachidonic acid group received it, until offspring age of three weeks. Six male offspring from each group were included in this study at ages of newborn, three-week-old, two-month-old, and their body measurements were recorded. Lumbar vertebrae and pancreas specimens were examined by light microscopy, morphometry, transmission electron microscopy (TEM), and immunohistochemistry for insulin expression. RESULTS: In alloxan-induced diabetes newborn, three-week-old, and two-month-old rats, body measurements were significantly declined, histomorphometry of 6th lumbar vertebrae revealed disorganized chondrocytes, with vacuolated cytoplasm, empty lacunae, diminished matrix staining, with areas devoid of cells. TEM showed shrunken reserve and proliferative cells, with irregular nuclei, and damaged mitochondria. In contrast, alloxan + arachidonic acid group had cytoarchitecture of lumbar vertebrae that were like control group. Histomorphometry of pancreas in alloxan-induced diabetes group showed significant reduction in pancreatic islets number and surface area, damaged pancreatic islet cells appeared atrophied with apoptotic nuclei, and very weak insulin immunostaining. Whereas alloxan + arachidonic acid group displayed healthy features of pancreatic islets, which resembled control group, with strong insulin immunostaining. CONCLUSIONS: Arachidonic acid mitigated alloxan-induced diabetes by its antidiabetic activity.
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Diabetes Mellitus Experimental , Islotes Pancreáticos , Aloxano/efectos adversos , Aloxano/metabolismo , Animales , Ácido Araquidónico/efectos adversos , Ácido Araquidónico/metabolismo , Glucemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Femenino , Insulina , Islotes Pancreáticos/metabolismo , Vértebras Lumbares/metabolismo , Masculino , Embarazo , RatasRESUMEN
In this post hoc study, arachidonic acid (AA)-induced platelet aggregation during pregnancy with and without acetylsalicylic acid (ASA) treatment was studied in 323 women with unexplained recurrent first-trimester miscarriage and in 59 healthy women with normal pregnancies. All women had normal AA-induced platelet aggregation in the non-pregnant state. Women with recurrent miscarriage were treated with 75 mg ASA or placebo daily. AA-induced platelet aggregation was measured with multiple electrode impedance aggregometry and presented in units (U), where 1 U = 10 aggregation units x minutes. There were no significant differences in platelet aggregation between placebo-treated women with recurrent miscarriage and healthy women. The mean differences were-0.7 (95%CI; -7.0; 5.6) U in the non-pregnant state, 3.8 (95%CI; -4.6; 12.2) U during the late first trimester and 1.7 (95%CI; -6.7; 10.3) U and 4.1 (95%CI; -3.9; 12.0) U during the early and late third trimester, respectively. ASA reduced platelet aggregation by median -84.0% (Q1; Q3; -89.8; -76.3), -79.9% (-84.7; -69.2) and -75.7% (-83.5; -49.5), respectively, during pregnancy. The degree of inhibition by ASA decreased during the third trimester (p < .0001). There were two (1.9%) complete non-responders to ASA and 32.1% with a partial response. The rate of subsequent miscarriage was not affected by ASA, which did not seem to influence the rate of early miscarriage if treatment was initiated when a viable pregnancy was detectable by ultrasound.
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Ácido Araquidónico/efectos adversos , Aspirina/efectos adversos , Agregación Plaquetaria/efectos de los fármacos , Aborto Habitual , Adulto , Estudios de Casos y Controles , Femenino , Humanos , EmbarazoRESUMEN
Importance: Supplementing preterm infants with long-chain polyunsaturated fatty acids (LC-PUFA) has been inconsistent in reducing the severity and incidence of retinopathy of prematurity (ROP). Furthermore, few studies have measured the long-term serum lipid levels after supplementation. Objective: To assess whether ROP severity is associated with serum levels of LC-PUFA, especially docosahexaenoic acid (DHA) and arachidonic acid (AA), during the first 28 postnatal days. Design, Setting, and Participants: This cohort study analyzed the Mega Donna Mega study, a randomized clinical trial that provided enteral fatty acid supplementation at 3 neonatal intensive care units in Sweden. Infants included in this cohort study were born at a gestational age of less than 28 weeks between December 20, 2016, and August 6, 2019. Main Outcomes and Measures: Severity of ROP was classified as no ROP, mild or moderate ROP (stage 1-2), or severe ROP (stage 3 and type 1). Serum phospholipid fatty acids were measured through gas chromatography-mass spectrometry. Ordinal logistic regression, with a description of unadjusted odds ratio (OR) as well as gestational age- and birth weight-adjusted ORs and 95% CIs, was used. Areas under the curve were used to calculate mean daily levels of fatty acids during postnatal days 1 to 28. Blood samples were obtained at the postnatal ages of 1, 3, 7, 14, and 28 days. Results: A total of 175 infants were included in analysis. Of these infants, 99 were boys (56.6%); the median (IQR) gestational age was 25 weeks 5 days (24 weeks 3 days to 26 weeks 6 days), and the median (IQR) birth weight was 785 (650-945) grams. A higher DHA proportion was seen in infants with no ROP compared with those with mild or moderate ROP or severe ROP (OR per 0.5-molar percentage increase, 0.49 [95% CI, 0.36-0.68]; gestational age- and birth weight-adjusted OR, 0.66 [95% CI, 0.46-0.93]). The corresponding adjusted OR for AA levels per 1-molar percentage increase was 0.83 (95% CI, 0.66-1.05). The association between DHA levels and ROP severity appeared only in infants with sufficient AA levels, suggesting that a mean daily minimum level of 7.8 to 8.3 molar percentage of AA was necessary for a detectable association between DHA level and less severe ROP. Conclusions and Relevance: This cohort study found that higher mean daily serum levels of DHA during the first 28 postnatal days were associated with less severe ROP even after adjustment for known risk factors, but only in infants with sufficiently high AA levels. Further studies are needed to identify LC-PUFA supplementation strategies that may prevent ROP and other morbidities.
Asunto(s)
Ácido Araquidónico/efectos adversos , Ácidos Docosahexaenoicos/efectos adversos , Retinopatía de la Prematuridad/etiología , Ácido Araquidónico/uso terapéutico , Estudios de Cohortes , Ácidos Docosahexaenoicos/uso terapéutico , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro/metabolismo , Recien Nacido Prematuro/fisiología , Modelos Logísticos , Masculino , Oportunidad Relativa , Retinopatía de la Prematuridad/epidemiología , SueciaRESUMEN
Non-alcoholic fatty liver disease impacts 15.2% of Hispanic adolescents and can progress to a build-up of scared tissue called liver fibrosis. If diagnosed early, liver fibrosis may be reversible, so it is necessary to understand risk factors. The aims of this study in 59 Hispanic adolescents with obesity were to: (1) identify potential biological predictors of liver fibrosis and dietary components that influence liver fibrosis, and (2) determine if the association between dietary components and liver fibrosis differs by PNPLA3 genotype, which is highly prevalent in Hispanic adolescents and associated with elevated liver fat. We examined liver fat and fibrosis, genotyped for PNPLA3 gene, and assessed diet via 24-h diet recalls. The prevalence of increased fibrosis was 20.9% greater in males, whereas participants with the GG genotype showed 23.7% greater prevalence. Arachidonic acid was associated with liver fibrosis after accounting for sex, genotype, and liver fat (ß = 0.072, p = 0.033). Intakes of several dietary types of unsaturated fat have different associations with liver fibrosis by PNPLA3 genotype after accounting for sex, caloric intake, and liver fat. These included monounsaturated fat (ßCC/CG = -0.0007, ßGG = 0.03, p-value = 0.004), polyunsaturated fat (ßCC/CG = -0.01, ßGG = 0.02, p-value = 0.01), and omega-6 (ßCC/CG = -0.0102, ßGG = 0.028, p-value = 0.01). Results from this study suggest that reduction of arachidonic acid and polyunsaturated fatty acid intake might be important for the prevention of non-alcoholic fatty liver disease progression, especially among those with PNPLA3 risk alleles.
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Ácido Araquidónico/efectos adversos , Grasas Insaturadas en la Dieta/efectos adversos , Hispánicos o Latinos/genética , Lipasa/genética , Cirrosis Hepática/etiología , Proteínas de la Membrana/genética , Obesidad Infantil/genética , Adiposidad , Adolescente , Niño , Femenino , Genotipo , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Cirrosis Hepática/genética , Masculino , Obesidad Infantil/complicaciones , Obesidad Infantil/metabolismo , Obesidad Infantil/patologíaRESUMEN
The association between dietary fat intake during pregnancy and the risk of developing preeclampsia has been examined in many epidemiological studies, but the results remain inconsistent. The aim of this study was to clarify this association in pregnant Chinese women. After conducting 1:1 matching, 440 pairs consisting of pregnant women with preeclampsia and hospital-based, healthy pregnant women matched by gestational week (± 1 week) and age (± 3 years) were recruited. A 79-item semi-quantitative food frequency questionnaire administered during face-to-face interviews was used to estimate the participants' dietary intake of fatty acids. We found that the intakes of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were inversely associated with the risk of developing preeclampsia. Compared with the lowest quartile intake, the multivariate-adjusted odds ratios (95% confidence interval) of the highest quartile intake were 0.42 (0.26-0.68, p-trend < 0.001) for EPA, 0.52 (0.3-0.83, p-trend = 0.005) for DHA, and 0.41 (0.19-0.88, p-trend = 0.007) for AA. However, we did not observe any significant associations between the intake of total fatty acids, saturated fatty acids, and mono-unsaturated fatty acids and the risk of developing preeclampsia. Our results showed that the dietary intake of long-chain polyunsaturated fatty acids (i.e., EPA, DHA, and AA) may protect pregnant Chinese women against the development of preeclampsia.
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Grasas de la Dieta/efectos adversos , Ácidos Grasos/efectos adversos , Preeclampsia/etiología , Adulto , Ácido Araquidónico/efectos adversos , Estudios de Casos y Controles , Ácido Eicosapentaenoico/efectos adversos , Femenino , Humanos , Embarazo , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
Blood flukes of the genus Schistosoma are covered by a protective heptalaminated, double lipid bilayer surface membrane. Large amounts of sphingomyelin (SM) in the outer leaflet form with surrounding water molecules a tight hydrogen bond barrier, which allows entry of nutrients and prevents access of host immune effectors. Excessive hydrolysis of SM to phosphoryl choline and ceramide via activation of the parasite tegument-associated neutral sphingomyelinase (nSMase) with the polyunsaturated fatty acid, arachidonic acid (ARA) leads to parasite death, via allowing exposure of apical membrane antigens to antibody-dependent cell-mediated cytotoxicity (ADCC), and accumulation of the pro-apoptotic ceramide. Surface membrane nSMase represents, thus, a worm Achilles heel, and ARA a valid schistosomicide. Several experiments conducted in vitro using larval, juvenile, and adult Schistosoma mansoni and Schistosoma haematobium documented ARA schistosomicidal potential. Arachidonic acid schistosomicidal action was shown to be safe and efficacious in mice and hamsters infected with S. mansoni and S. haematobium, respectively, and in children with light S. mansoni infection. A combination of praziquantel and ARA led to outstanding cure rates in children with heavy S. mansoni infection. Additionally, ample evidence was obtained for the powerful ARA ovocidal potential in vivo and in vitro against S. mansoni and S. haematobium liver and intestine eggs. Studies documented ARA as an endogenous schistosomicide in the final mammalian and intermediate snail hosts, and in mice and hamsters, immunized with the cysteine peptidase-based vaccine. These findings together support our advocating the nutrient ARA as the safe and efficacious schistosomicide of the future.
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Antígenos Helmínticos/administración & dosificación , Ácido Araquidónico/uso terapéutico , Proteasas de Cisteína/administración & dosificación , Schistosoma/efectos de los fármacos , Esquistosomiasis/tratamiento farmacológico , Esquistosomicidas/uso terapéutico , Vacunas/administración & dosificación , Animales , Antígenos Helmínticos/inmunología , Ácido Araquidónico/efectos adversos , Ácido Araquidónico/metabolismo , Proteasas de Cisteína/inmunología , Modelos Animales de Enfermedad , Interacciones Huésped-Parásitos , Humanos , Recuento de Huevos de Parásitos , Schistosoma/inmunología , Schistosoma/patogenicidad , Esquistosomiasis/inmunología , Esquistosomiasis/metabolismo , Esquistosomiasis/parasitología , Esquistosomicidas/efectos adversos , Resultado del Tratamiento , Vacunación , Vacunas/inmunologíaRESUMEN
Long-chain polyunsaturated fatty acids modulate bone mass and adipocyte metabolism. Arachidonic acid (AA, C20:4 n-6) is elevated in obesity and postulated to stimulate bone resorption. This study aimed to determine the effect of AA on bone mass, quality, and adiposity in diet-induced obesity during growth. Male Sprague-Dawley rats (n=42, 4-week) were randomized into groups fed a control diet (CTRL, AIN-93G), high-fat diet (HFD, 35% kcal fat) or HFDâ¯+â¯AA (1% w/w diet) for 6 weeks. Body composition, bone mineral density and microarchitecture were measured using dual-energy X-ray absorptiometry and micro-computed tomography. Red blood cell fatty acid profile was measured with gas chromatography. Group differences were evaluated using repeated measures two-way analysis of variance with Tukey-Kramer post hoc testing. Total energy intake did not differ among diet groups. At week 6, HFDâ¯+â¯AA had significantly greater body fat % (12%), body weight (6%) and serum leptin concentrations (125%) than CTRL, whereas visceral fat (mass and %, assessed with micro-computed tomography) was increased in both HFD and HFDâ¯+â¯AA groups. HFDâ¯+â¯AA showed reduced whole body bone mineral content and femur mid-diaphyseal cortical bone cross-sectional area than HFD and CTRL, without impairment in bone strength. Contrarily, HFDâ¯+â¯AA had greater femur metaphyseal trabecular vBMD (35%) and bone volume fraction (5%) compared to controls. Inclusion of AA elevated leptin concentrations in male rats. The early manifestations of diet-induced obesity on bone mass were accelerated with AA. Studies of longer duration are needed to clarify the effect of AA on peak bone mass following growth cessation.
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Ácido Araquidónico/efectos adversos , Densidad Ósea/efectos de los fármacos , Huesos/fisiopatología , Dieta Alta en Grasa/efectos adversos , Obesidad/etiología , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Adiposidad/efectos de los fármacos , Animales , Ácido Araquidónico/administración & dosificación , Fenómenos Biomecánicos , Composición Corporal/efectos de los fármacos , Resorción Ósea/etiología , Huesos/efectos de los fármacos , Ingestión de Energía , Ácidos Grasos/farmacología , Fémur/efectos de los fármacos , Fémur/patología , Leptina/sangre , Masculino , Ratones , Obesidad/patología , Obesidad/fisiopatología , Ratas , Ratas Sprague-DawleyRESUMEN
Oxylipids are potent lipid mediators associated with inflammation-induced colon carcinomas and colon tumor survival. Therefore, oxylipid profiles may be useful as novel biomarkers of colon polyp presence. The aim of this study was to investigate the relationship between plasma non-esterified oxylipids and the presence of colon polyps. A total of 123 Caucasian men, ages 48 to 65, were categorized into three groups: those with no polyps, those with one or more hyperplastic polyps, and those with one or more adenomas. Plasma non-esterified oxylipids were analyzed using solid phase extraction and quantified using a targeted HPLC tandem mass spectrometric analysis. Statistical analyses included Kruskal-Wallis one-way ANOVA with Dunn's test for multiple comparison and generalized linear models to adjust for confounding factors such as age, anthropometrics, and smoking status. In general, monohydroxy omega-6-derived oxylipids were significantly increased in those with polyps. Concentrations of 5-hydroxyeicosatetraenoic acid (HETE) and 11-HETE were significantly higher in those with hyperplastic polyps and adenomas compared to those with no polyps. Arachidonic acid-derived HETEs were significantly associated with colon polyp types, even after adjusting for age, smoking, and body mass index or waist circumference in regression models. Since many of these oxylipids are formed through oxygenation by lipoxygenases (i.e., 5-, 12-, and 15-HETE, and 15- hydroxyeicosatrienoic acid [HETrE]) or auto-oxidative reactions (i.e., 11-HETE), this may indicate that lipoxygenase activity and lipid peroxidation are increased in those with colon polyps. In addition, since oxylipids such as 5-, 12-, and 15-HETE are signaling molecules involved in inflammation regulation, these oxylipids may have important functions in inflammation-associated polyp presence. Future studies should be performed in a larger cohorts to investigate if these oxylipids are useful as potential biomarkers of colon polyps.
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Ácido Araquidónico/efectos adversos , Pólipos del Colon/epidemiología , Pólipos del Colon/etiología , Ácidos Hidroxieicosatetraenoicos/efectos adversos , Factores de Edad , Anciano , Ácido Araquidónico/sangre , Ácido Araquidónico/metabolismo , Biomarcadores , Pólipos del Colon/diagnóstico , Estudios Transversales , Susceptibilidad a Enfermedades , Ácidos Grasos Omega-3/sangre , Humanos , Ácidos Hidroxieicosatetraenoicos/sangre , Ácidos Hidroxieicosatetraenoicos/metabolismo , Lipidómica , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de RiesgoRESUMEN
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.
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Ácido Araquidónico/administración & dosificación , Suplementos Dietéticos , Ácidos Docosahexaenoicos/administración & dosificación , Fenilcetonurias/dietoterapia , Adolescente , Adulto , Ácido Araquidónico/efectos adversos , Niño , Preescolar , Cognición , Dieta con Restricción de Proteínas , Suplementos Dietéticos/efectos adversos , Ácidos Docosahexaenoicos/efectos adversos , Potenciales Evocados Motores , Potenciales Evocados Visuales , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Fenilcetonurias/diagnóstico , Fenilcetonurias/fisiopatología , Fenilcetonurias/psicología , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Adulto JovenRESUMEN
RATIONALE: Evidence linking saturated fat intake with cardiovascular health is controversial. The associations of unsaturated fats with total and cardiovascular disease (CVD) mortality remain inconsistent, and data about non-CVD mortality are limited. OBJECTIVE: To assess dietary fat intake in relation to total and cause-specific mortality. METHODS AND RESULTS: We analyzed data of 521 120 participants aged 50 to 71 years from the National Institutes of Health-American Association of Retired Persons Diet and Health Study with 16 years of follow-up. Intakes of saturated fatty acids (SFAs), trans-fatty acids, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) were assessed via food frequency questionnaires. Hazard ratios and 95%CIs were estimated using the Cox proportional hazards model. Overall, 129 328 deaths were documented during 7.3 million person-years of follow-up. In the replacement of carbohydrates, multivariable-adjusted hazard ratios of total mortality comparing extreme quintiles were 1.29 (95% CI, 1.25-1.33) for SFAs, 1.03 (1.00-1.05) for trans-fatty acids, 0.98 (0.94-1.02) for MUFAs, 1.09 (1.06-1.13) for animal MUFAs, 0.94 (0.91-0.97) for plant MUFAs, 0.93 (0.91-0.95) for PUFAs, 0.92 (0.90-0.94) for marine omega-3 PUFAs, 1.06 (1.03-1.09) for α-linolenic acid, 0.88 (0.86-0.91) for linoleic acid, and 1.10 (1.08-1.13) for arachidonic acid. CVD mortality was inversely associated with marine omega-3 PUFA intake ( P trend <0.0001), whereas it was positively associated with SFA, trans-fatty acid, and arachidonic acid intake. Isocalorically replacing 5% of the energy from SFAs with plant MUFAs was associated with 15%, 10%, 11%, and 30% lower total mortality, CVD, cancer, and respiratory disease mortality, respectively. Isocaloric replacement of SFA with linoleic acid (2%) was associated with lower total (8%), CVD (6%), cancer (8%), respiratory disease (11%), and diabetes mellitus (9%) mortality. CONCLUSIONS: Intakes of SFAs, trans-fatty acids, animal MUFAs, α-linolenic acid, and arachidonic acid were associated with higher mortality. Dietary intake of marine omega-3 PUFAs and replacing SFAs with plant MUFAs or linoleic acid were associated with lower total, CVD, and certain cause-specific mortality. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00340015.
Asunto(s)
Enfermedades Cardiovasculares/mortalidad , Grasas de la Dieta/efectos adversos , Ácidos Grasos/efectos adversos , Anciano , Ácido Araquidónico/administración & dosificación , Ácido Araquidónico/efectos adversos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/prevención & control , Causas de Muerte , Grasas de la Dieta/administración & dosificación , Ácidos Grasos/administración & dosificación , Ácidos Grasos Monoinsaturados/administración & dosificación , Ácidos Grasos Monoinsaturados/efectos adversos , Ácidos Grasos Omega-3/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores Protectores , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Ácidos Grasos trans/administración & dosificación , Ácidos Grasos trans/efectos adversos , Estados Unidos/epidemiología , Ácido alfa-Linolénico/administración & dosificación , Ácido alfa-Linolénico/efectos adversosRESUMEN
BACKGROUND: The obesity paradox in COPD describes protective effects of obesity on lung pathology and inflammation. However, the underlying relationships between obesity, diet and disease outcomes in COPD are not fully understood. In this study we measured the response to dietary fatty acids upon markers of inflammation and remodelling in human lung cells from people with and without COPD. METHODS: Pulmonary fibroblasts were challenged with ω-3 polyunsaturated fatty acids (PUFAs), ω-6 PUFAs, saturated fatty acids (SFAs) or the obesity-associated cytokine TNFα. After 48-72 h release of the pro-inflammatory cytokines interleukin (IL)-6 and CXCL8 was measured using ELISA and mRNA expression and deposition of the extracellular matrix (ECM) proteins fibronectin, type I collagen, tenascin and perlecan were measured using qPCR or ECM ELISA, respectively. RESULTS: Challenge with the ω-6 PUFA arachidonic acid (AA), but not ω-3 PUFAs or SFAs, resulted in increased IL-6 and CXCL8 release from fibroblasts, however IL-6 and CXCL8 release was reduced in COPD (n = 19) compared to non-COPD (n = 36). AA-induced cytokine release was partially mediated by downstream mediators of cyclooxygenase (COX)-2 in both COPD and non-COPD. In comparison, TNFα-induced IL-6 and CXCL8 release was similar in COPD and non-COPD, indicating a specific interaction of AA in COPD. In patients with or without COPD, regression analysis revealed no relationship between BMI and cytokine release. In addition, AA, but not SFAs or ω-3 PUFAs reduced the basal deposition of fibronectin, type I collagen, tenascin and perlecan into the ECM in COPD fibroblasts. In non-COPD fibroblasts, AA-challenge decreased basal deposition of type I collagen and perlecan, but not fibronectin and tenascin. CONCLUSIONS: This study shows that AA has disease-specific effects on inflammation and ECM protein deposition. The impaired response to AA in COPD might in part explain why obesity appears to have less detrimental effects in COPD, compared to other lung diseases.
Asunto(s)
Ácido Araquidónico/efectos adversos , Proteínas de la Matriz Extracelular/antagonistas & inhibidores , Proteínas de la Matriz Extracelular/biosíntesis , Ácidos Grasos Omega-6/efectos adversos , Mediadores de Inflamación/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Adulto , Anciano , Ácido Araquidónico/farmacología , Células Cultivadas , Proteínas de la Matriz Extracelular/genética , Ácidos Grasos Omega-6/farmacología , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Expresión Génica , Humanos , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/patología , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/patologíaRESUMEN
Dietary fatty acids are associated with the development of many chronic diseases, such as obesity, diabetes, cardiovascular disease, metabolic syndrome, and several cancers. This review explores the literature surrounding the combined and individual roles of n-6 PUFAs linoleic acid (LA) and arachidonic acid (AA) as they relate to immune and inflammatory response, cardiovascular health, liver health, and cancer. The evidence suggests that a pro-inflammatory view of LA and AA may be over simplified. Overall, this review highlights gaps in our understanding of the biological roles of LA, AA and their complex relationship with n-3 PUFA and the need for future studies that examine the roles of individual fatty acids, rather than groups.
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Ácido Araquidónico/efectos adversos , Ácido Araquidónico/metabolismo , Ácido Linoleico/efectos adversos , Ácido Linoleico/metabolismo , Animales , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/metabolismo , Grasas Insaturadas en la Dieta/efectos adversos , Grasas Insaturadas en la Dieta/metabolismo , Técnicas de Inactivación de Genes , Humanos , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/metabolismo , Linoleoil-CoA Desaturasa/genética , Linoleoil-CoA Desaturasa/metabolismo , Hepatopatías/etiología , Hepatopatías/genética , Hepatopatías/metabolismo , Neoplasias/inducido químicamente , Neoplasias/genética , Neoplasias/metabolismoRESUMEN
The aim of this study was to evaluate the anti-edematogenic activity of X. americana L. (HEXA) hydroethanolic extract in ear edema models (acute and chronic) induced by croton oil and by different phlogistic agents (arachidonic acid, capsaicin, phenol and histamine), identifying the possible anti-edematogenic mechanism. HEXA demonstrated a significant anti-edematogenic effect at concentrations of 100-500⯵g/ear in ear edema induced by croton oil with higher inhibition of edema of 39.37. However, the concentrations of 100 and 200⯵g/ear were taken as a standard, demonstrating the effect in the chronic model induced by croton oil with inhibition of 61.62% and 48.74%. In the AA-induced ear edema model, HEXA showed inhibition of: 24.45% and 32.31%; capsaicin inhibition of 72.72% and 47.57%; phenol inhibition of 34% and 20.1%; and histamine inhibition of 31.8% and 21.62%. Then, the results were showed that HEXA demonstrated an anti-edematogenic effect in acute and chronic inflammation models, demonstrating a probable mechanism of action by the inhibition or modulation of key mediators of the inflammatory process. The chemical profile and presence of flavonoids guaranteeing a profile of activity similar to natural drugs that act or modulate the production of mediators of inflammations.
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Cromatografía Líquida de Alta Presión/métodos , Dermatitis/tratamiento farmacológico , Edema/tratamiento farmacológico , Olacaceae/química , Extractos Vegetales/uso terapéutico , Animales , Ácido Araquidónico/efectos adversos , Ácido Araquidónico/antagonistas & inhibidores , Capsaicina/efectos adversos , Capsaicina/antagonistas & inhibidores , Aceite de Crotón/toxicidad , Relación Dosis-Respuesta a Droga , Edema/inducido químicamente , Femenino , Histamina/efectos adversos , Antagonistas de los Receptores Histamínicos/uso terapéutico , Ratones , Fenol/efectos adversos , Fenol/antagonistas & inhibidoresRESUMEN
Dietary n-6 polyunsaturated fatty acids (PUFA) are widely perceived to promote inflammation and contribute to the development of chronic diseases. This dogma has been recently questioned due to evidence that n-6 PUFA, specifically linoleic acid (LA, 18:2n-6) and arachidonic acid (AA, 20:4n-6), do not appear to activate inflammatory signalling pathways when consumed in moderate amounts. However, delineating the independent roles of different dietary n-6 PUFA in vivo is challenging because LA is continuously converted into AA in a pathway regulated by the fatty acid desaturase 2 (Fads2) gene. The objective of this study was to investigate the independent roles of LA and AA on white adipose tissue (WAT) inflammatory signalling pathways using Fads2-/- mice. We hypothesized that dietary LA would not induce WAT inflammation, unless it was endogenously converted into AA. Male C57BL/6 wild-type (WT) and Fads2-/- mice were fed low-fat isocaloric diets containing either 7% corn oil w/w (CD, containing ~42% LA) or 7% ARASCO oil w/w (AD, containing ~27% AA) for 9 weeks. WAT inflammatory gene expression, protein levels, as well as phospholipid (PL) and triacylglycerol (TAG) fatty acid composition, were analyzed by RT-qPCR, western blots, and gas chromatography, respectively. Fads2-/- mice fed CD had high LA, but little-to-no GLA (18:3n-6), DGLA (20:3n-6), and AA in PLs and TAGs compared to their WT counterparts. In comparison, Fads2-/- and WT mice fed AD showed minimal differences in n-6 PUFA content in serum and WAT, despite having significantly more AA than CD-fed mice. No differences in gene expression for common inflammatory adipokines (e.g. Mcp-1, Ccl5, Tnfα) or key regulators of eicosanoid production (e.g. Cox-2, Alox-12, Alox-15) were detected in WAT between any of the diet and genotype groups. Furthermore, no differences in MCP-1, and total or phosphorylated STAT3 and p38 inflammatory proteins, were observed. Collectively, these results demonstrate that neither LA nor AA promote WAT inflammation when consumed as part of a low-fat diet. Therefore, the existing dogma surrounding n-6 PUFA and inflammation needs to be reconsidered.
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Ácido Araquidónico/administración & dosificación , Ácido Graso Desaturasas/genética , Inflamación/metabolismo , Ácido Linoleico/administración & dosificación , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo Blanco/efectos de los fármacos , Tejido Adiposo Blanco/metabolismo , Animales , Ácido Araquidónico/efectos adversos , Dieta con Restricción de Grasas/efectos adversos , Grasas de la Dieta/metabolismo , Ácido Graso Desaturasas/metabolismo , Ácidos Grasos Insaturados/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/patología , Ácido Linoleico/efectos adversos , Metabolismo de los Lípidos/genética , Ratones , Fosfolípidos/metabolismo , Transducción de Señal/efectos de los fármacos , Triglicéridos/metabolismoRESUMEN
Little is known about arachidonic acid (ARA) and docosahexaenoic acid (DHA) requirements in toddlers. A longitudinal, double blind, controlled trial in toddlers ( n = 133) age 13.4 ± 0.9 months (mean ± standard deviation), randomized to receive a DHA (200 mg/day) and ARA (200 mg/day) supplement (supplement) or a corn oil supplement (control) until age 24 months determined effects on neurodevelopment. We found no effect of the supplement on the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) cognitive and language composites and Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery VMI) at age 24 months. Supplemented toddlers had higher RBC phosphatidylcholine (PC), phosphatidylethanolamine (PE), and plasma DHA and ARA compared to placebo toddlers at age 24 months. A positive relationship between RBC PE ARA and Bayley III Cognitive composite (4.55 (0.21-9.00), B (95% CI), p = 0.045) in supplemented boys, but not in control boys, was observed in models adjusted for baseline fatty acid, maternal non-verbal intelligence, and BMI z-score at age 24 months. A similar positive relationship between RBC PE ARA and Bayley III Language composite was observed for supplemented boys (11.52 (5.10-17.94), p < 0.001) and girls (11.19 (4.69-17.68), p = 0.001). These findings suggest that increasing the ARA status in toddlers is associated with better neurodevelopment at age 24 months.
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Ácido Araquidónico/administración & dosificación , Desarrollo Infantil , Ácidos Docosahexaenoicos/administración & dosificación , Factores de Edad , Ácido Araquidónico/efectos adversos , Ácido Araquidónico/sangre , Colombia Británica , Lenguaje Infantil , Preescolar , Cognición , Suplementos Dietéticos/efectos adversos , Ácidos Docosahexaenoicos/efectos adversos , Ácidos Docosahexaenoicos/sangre , Método Doble Ciego , Eritrocitos/metabolismo , Femenino , Humanos , Lactante , Inteligencia , Masculino , Fosfatidilcolinas/sangre , Fosfatidiletanolaminas/sangre , Estudios Prospectivos , Desempeño Psicomotor , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Polyunsaturated fatty acids play a crucial role in neuronal function, and the modification of these compounds in the brain could have an impact on neurodegenerative diseases such as Alzheimer's disease. Despite the fact that arachidonic acid is the second foremost polyunsaturated fatty acid besides docosahexaenoic acid, its role and the regulation of its transfer and mobilization in the brain are poorly known. METHODS: Two groups of 39 adult male BALB/c mice were fed with an arachidonic acid-enriched diet or an oleic acid-enriched diet, respectively, for 12 weeks. After 10 weeks on the diet, mice received intracerebroventricular injections of either NaCl solution or amyloid-ß peptide (Aß) oligomers. Y-maze and Morris water maze tests were used to evaluate short- and long-term memory. At 12 weeks on the diet, mice were killed, and blood, liver, and brain samples were collected for lipid and protein analyses. RESULTS: We found that the administration of an arachidonic acid-enriched diet for 12 weeks induced short-term memory impairment and increased deleterious effects of Aß oligomers on learning abilities. These cognitive alterations were associated with modifications of expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, postsynaptic density protein 95, and glial fibrillary acidic protein in mouse cortex or hippocampus by the arachidonic acid-enriched diet and Aß oligomer administration. This diet also led to an imbalance between the main ω-6 fatty acids and the ω-3 fatty acids in favor of the first one in erythrocytes and the liver as well as in the hippocampal and cortical brain structures. In the cortex, the dietary arachidonic acid also induced an increase of arachidonic acid-containing phospholipid species in phosphatidylserine class, whereas intracerebroventricular injections modified several arachidonic acid- and docosahexaenoic acid-containing species in the four phospholipid classes. Finally, we observed that dietary arachidonic acid decreased the expression of the neuronal form of acyl-coenzyme A synthetase 4 in the hippocampus and increased the cytosolic phospholipase A2 activation level in the cortices of the mice. CONCLUSIONS: Dietary arachidonic acid could amplify Aß oligomer neurotoxicity. Its consumption could constitute a risk factor for Alzheimer's disease in humans and should be taken into account in future preventive strategies. Its deleterious effect on cognitive capacity could be linked to the balance between arachidonic acid-mobilizing enzymes.
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Péptidos beta-Amiloides/toxicidad , Ácido Araquidónico/efectos adversos , Dieta/efectos adversos , Aprendizaje por Laberinto/fisiología , Fragmentos de Péptidos/toxicidad , Receptores AMPA/metabolismo , Animales , Ácido Araquidónico/administración & dosificación , Astrocitos/metabolismo , Proliferación Celular/fisiología , Corteza Cerebral/metabolismo , Coenzima A Ligasas/metabolismo , Citosol/metabolismo , Homólogo 4 de la Proteína Discs Large/metabolismo , Hipocampo/metabolismo , Masculino , Trastornos de la Memoria/etiología , Trastornos de la Memoria/fisiopatología , Ratones Endogámicos BALB C , Neuronas/metabolismo , Ácido Oléico/administración & dosificación , Fosfolipasas A2/metabolismo , Factores de RiesgoRESUMEN
In the present study, an effort was made to design poly (D, L-lactide-co-glycolide) acid nanoparticles of aceclofenac by direct precipitation method. The nanoparticles were found to have adequate particle size range for ocular administration of 162.6 to 244.13 nm with nearly spherical shape and with zeta potential of - 21.5 to - 25.5 mV. Drug entrapment efficiency of nanoparticle formulations ranged from 42.9 to 92.68%. Differential scanning calorimetric (DSC) and powder X-ray diffraction (PXRD) studies depicted that the drug incorporated in nanoparticles was found to be in amorphous state. Moreover, nanoparticles showed prolonged in vitro drug release profile and followed Higuchi-square-root release kinetics. Nanoparticles showed two folds higher permeation than aqueous solution of aceclofenac. Nanoparticles were well tolerated with no signs of corneal damage in in vitro transcorneal permeation studies. The formulation was quite stable. In vivo ocular anti-inflammatory study in the rabbit eyes confirmed better efficacy of nanoparticles as compared with the aqueous solution and its potential application in ocular inflammatory conditions.