12(S)-Hydroxyheptadeca-5Z,8E,10E-trienoic acid suppresses UV-induced IL-6 synthesis in keratinocytes, exerting an anti-inflammatory activity

12(S)-Hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) is an enzymatic product of prostaglandin H2 (PGH2) derived from cyclooxygenase (COX)-mediated arachidonic acid metabolism. Despite the high level of 12-HHT present in tissues and bodily fluids, its precise function remains largely unknown. In this study, we found that 12-HHT treatment in HaCaT cells remarkably down-regulated the ultraviolet B (UVB) irradiation-induced synthesis of interleukin-6 (IL-6), a pro-inflammatory cytokine associated with cutaneous inflammation. In an approach to identify the down-stream signaling mechanism by which 12-HHT down-regulates UVB-induced IL-6 synthesis in keratinocytes, we observed that 12-HHT inhibits the UVB-stimulated activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-kappaB). In addition, we found that 12-HHT markedly up-regulates MAPK phosphatase-1 (MKP-1), a critical negative regulator of p38 MAPK. When MKP-1 was suppressed by siRNA knock-down, the 12-HHT-mediated inhibitory effects on the UVB-stimulated activation of p38 MAPK and NF-kappaB, as well as the production of IL-6, were attenuated in HaCaT cells. Taken together, our results suggest that 12-HHT exerts anti-inflammatory effect via up-regulation of MKP-1, which negatively regulates p38 MAPK and NF-kappaB, thus attenuating IL-6 production in UVB-irradiated HaCaT cells. Considering the critical role of IL-6 in cutaneous inflammation, our findings provide the basis for the application of 12-HHT as a potential anti-inflammatory therapeutic agent in UV-induced skin diseases.

Influências de dietas ricas em ácidos graxos saturados e insaturados sobre o miocárdio de ratos / Influences of rich in saturated and unsaturated fatty acids diets in rat myocardium

OBJETIVOS: O estudo avaliou a influência de dietas ricas em ácidos graxos saturados (AGS) e ácidos graxos insaturados (AGI) sobre a função mecânica, a morfologia e o estresse oxidativo do miocárdio de ratos. MÉTODOS: Ratos Wistar com 60 dias de idade foram alimentados com dieta padrão (n = 8) ou dietas ricas em AGS (n = 8) ou AGI (n = 8) durante 60 dias. A função mecânica foi avaliada em músculo papilar isolado do ventrículo esquerdo (VE) por meio de contrações isométrica e isotônica, em condição basal (1,25 mM de cálcio), após elevação da concentração extracelular de cálcio para 5,2 mM e estimulação beta-adrenérgica com isoproterenol 1,0 µM. Fragmentos do VE foram usados para estudo de estresse oxidativo e microscopias óptica e eletrônica. RESULTADOS: As dietas suplementadas com AGS e AGI não alteraram a função mecânica do músculo cardíaco. Entretanto, ambas provocaram estresse oxidativo, com aumento do hidroperóxido de lipídio e redução da concentração de superóxido dismutase. A dieta AGI diminuiu a expressão da catalase e a AGS reduziu a quantidade de glutationa peroxidase miocárdica. Ambas as dietas promoveram discretas alterações morfológicas visualizadas ultra-estruturalmente, como depósitos lipídicos e lesões das membranas celulares. CONCLUSÃO: Os resultados sugerem que dietas enriquecidas com AGS e AGI não acarretam alteração da função mecânica do músculo cardíaco isolado, mas causam discretas lesões estruturais e estresse oxidativo no miocárdio.

OBJECTIVES: To study the influence of saturated (SFA) and unsaturated fatty acid (UFA) rich diets on mechanical function, morphology and oxidative stress in rat myocardium. METHODS: Male, 60-day-old Wistar rats were fed a control (n=8), a SFA (n=8), or a UFA-rich diet (n=8) for sixty days. Mechanical function was studied in isolated left ventricle papillary muscle under isometric and isotonic contractions, in basal conditions (1.25mM calcium chloride) and after 5.2mM calcium chloride and beta-adrenergic stimuli with 1.0µM isoproterenol. Left ventricle fragments were used to study oxidative stress and morphology under light and electron microscopy. RESULTS: SFA and UFA-rich diets did not change myocardium mechanical function. Both diets caused oxidative stress, with high lipid hydroperoxide and low superoxide-dismutase concentrations. UFA rich diet decreased catalase expression and SFA rich diet decreased the amount of myocardial glutathione-peroxidase. Both diets promoted light ultrastructural injuries such as lipid deposits and cell membrane injuries. CONCLUSION: Results suggest that SFA and UFA rich diets do not alter isolated muscle mechanical function, but promote light myocardial morphological injuries and oxidative stress.

Effect of unsaturated fatty acids on myocardial performance, metabolism and morphology

Diets rich in saturated fatty acids are one of the most important causes of atherosclerosis in men, and have been replaced with diets rich in unsaturated fatty acids (UFA) for the prevention of this disorder. However, the effect of UFA on myocardial performance, metabolism and morphology has not been completely characterized. The objective of the present investigation was to evaluate the effects of a UFA-rich diet on cardiac muscle function, oxidative stress, and morphology. Sixty-day-old male Wistar rats were fed a control (N = 8) or a UFA-rich diet (N = 8) for 60 days. Myocardial performance was studied in isolated papillary muscle by isometric and isotonic contractions under basal conditions after calcium chloride (5.2 mM) and ß-adrenergic stimulation with 1.0 æM isoproterenol. Fragments of the left ventricle free wall were used to study oxidative stress and were analyzed by light microscopy, and the myocardial ultrastructure was examined in left ventricle papillary muscle. After 60 days the UFA-rich diet did not change myocardial function. However, it caused high lipid hydroperoxide (176 ± 5 vs 158 ± 5, P < 0.0005) and low catalase (7 ± 1 vs 9 ± 1, P < 0.005) and superoxide-dismutase (18 ± 2 vs 27 ± 5, P < 0.005) levels, and discrete morphological changes in UFA-rich diet hearts such as lipid deposits and mitochondrial membrane alterations compared to control rats. These data show that a UFA-rich diet caused myocardial oxidative stress and mild structural alterations, but did not change mechanical function.

Macromolecular synthesis in wing discs of Spodoptera mauritia Boisd: effects of a juvenile hormone analogue.

Last instar larvae of S. mauritia treated topically on day 0, day 1, day 2 and day 3 with a daily (dose of 25 microg juvenile hormone analogue (JHA) moulted into supernumerary larvae. The imaginal discs of the supernumerary larvae especially those of mouthparts and thoracic appendages showed pupal characteristics. However the wing discs, which showed only partial differentiation, were uneverted and highly tanned. In an effort to provide an explanation to this anomaly the RNA, DNA and protein profile in the wing discs of supernumerary larvae were studied. Quantitative analysis of DNA, RNA and protein showed a considerable increase in the amount of DNA and protein and a decline in RNA level. SDS-PAGE analysis of wing disc proteins of JHA treated larvae showed a reduction in the expression of many major proteins that were predominant in the wing discs of control larvae. The results suggest that JHA induced inactivation of genes involved in the synthesis of proteins needed for evagination process may be responsible for the formation of uneverted, partially differentiated pupal wing discs in supernumerary larvae.

Acido linoleico conjugado: un ácido graso con isomeria trans potencialmente beneficioso / Conjugated linoleic acid: a trans isomer fatty acid potentially beneficial

El ácido linoleico conjugado (ALC) es un ácido graso que presenta un tipo de isomeria trans, y que tiene variados efectos beneficiosos para la salud. La estructura de ALC más común que existe en la naturaleza, corresponde a la configuración de isómero 9c (cis), 11t (trans). El ALC se encuentra normalmente en tejidos y/o secreciones (leche) de rumiantes y es formado por la isomerización del ácido linoleico, por acción de la bacteria del rúmen llamada Butyrivibrio fibrisolven. ALC puede ser sintetizado, tanto en rumiantes como en no rumiantes, por la desaturación del ácido vaccenico (18:1, 11t) en el tracto intestinal y/o en el hígado de estos animales. La ingestión diaria de ALC es muy variable (0,5g/día-1,5g/día), ya que depende por una parte de los hábitos nutricionales ya sea individuales o regionales, o por otra, del consumo de carne, leche o derivados de la leche. Se han descritos diversas propiedades nutricionales y biológicas para los diversos isómeros de ALC, entre las más relevantes se destacan: su efecto hipocolesterolémico y antiaterogénico, su acción inmuno-estimulante, la protección que ofrece contra cierto tipo de cánceres, su función antioxidante y la participación en la reducción de peso corporal. Sin embargo, la confirmación definitiva de todos estos efectos beneficiosos para la salud, requiere de un mayor cuerpo de evidencias clínicas y experimentales que avalen sin lugar a dudas estas acciones de ALC. En la actualidad, diversos productos que contienen ALC se ofrecen en los mercados para la venta, los de mayor éxito, son aquellos productos que muestran que los isómeros de ALC que contienen, permiten reducir peso

Polyunsaturated fatty acids (PUFA) regulate neurotransmitter contents in rat brain.

The effects of feeding of 6-propylthiouracil (6-PTU) and polyunsaturated fatty acids (PUFA) independently and in combination and administration (ip) of a single dose of triiodothyronine (T3) (2.5 microg/100 g body wt) along with feeding of 6-PTU and PUFA were studied in rat brain. Dopamine (DA), 5-hydroxytryptophan (5-HTP), serotonin (5-HT), 5-hydroxy indole acetic acid (5-HIAA), norepinephrine (NE) and epinephrine (EPI) contents were assayed in the hypothalamus and cerebral cortex regions. It was found that 6-PTU feeding resulted in decrease in dopamine, 5-HT, 5-HTP and 5-HIAA in both regions. In animals fed with PUFA followed by administration of T3, the DA level was found normal.

Morphogenetic derangements in the reproductive system of Bracon hebetor, a beneficial parasitoid, bred on juvenoid treated host (Corcyra cephalonica) larvae.

Effect of juvenoids (hydroprene and methoprene) on the ecto-parasite B. hebetor was investigated by rearing them upon the juvenoid treated ultimate instar host larvae of C. cephalonica. Emerged adultoid wasps of either sexes obtained from treated series showed anatomical deformities in the reproductive systems. Ill-developed ovaries with reduced length, terminally free ovarioles and abnormal testicular growth showing non-fusion of lobes were the important abnormal features. Data on measurements of male reproductive system, e.g., width (transverse axis) of testis, length of common vas deferens plus ejaculatory duct and length of accessory gland showed significant difference (P < 0.05) from control.

Importancia nutricional de los ácidos grasos poliinsaturados n-3 de cadena larga: el beneficio de su suplementación / Nutritional importance of n-3 long-chain poly unsaturated fatty acids: the benefits of supplementation

Durante las últimas dos décadas se ha generado una importante información científica y un creciente interés sobre la función nutricional de los ácidos grasos poliinsaturados de cadena larga n-3. Estos ácidos grasos son esenciales en muchas funciones bioquímicas, y aunque se requieren en pequeñas cantidades, los humanos tienen muchas limitaciones para formarlos a partir de precursores más simples, por lo cual deben estar presentes en la dieta. Los recién nacidos y los adultos con predisposición al desarrollo de enfermedades cardiovasculares constituyen los grupos más vulnerables a la deficiencia de estos ácidos grasos. La dieta consumida en la mayoría de los países occidentales aporta pequeñas cantidades de ácidos grasos poliinsaturados de cadena larga n-3, por lo cual se considera que existe una carencia crónica nutricional de estos ácidos grasos, que es particularmente importante en los recién nacidos y en los lactantes. Se han desarrollado numerosos esfuerzos para suplementar nuestra alimentación con estos ácidos grasos, desde promover el consumo de aquellos peces que los contienen en alta cantidad, o el desarrollo de productos enriquecidos con estos ácidos grasos, la manipulación de la dieta de los animales que constituyen nuestra alimentación con el propósito de enriquecer sus tejidos con estos nutrientes, hasta el uso de procedimientos biotecnológicos para preparar productos que los contienen en altas concentraciones y que son de alta biodisponibilidad. El propósito de este trabajo es revisar en forma crítica aspectos relacionados con la esencialidad, los requerimientos y las vías de obtención con fines nutricionales de los ácidos grasos poliinsaturados de cadena larga n-3

The effects of fatty acids on lymphocyte functions

1. Lymphocytes play an important role in cell-mediated immunity and have been implicated in inflammatory and autoimmune diseases. 2. Unsaturated fatty acids, including oleic, linoleic, alpha-linolenic, arachidonic, eicosapentaenoic and docosahexaenoic acids, inhibit mitogen-stimulated lymphocyte proliferation in vitro. The inhibition of proliferation is dependent upon the concentration of fatty acid, the time during culture of fatty acid addition, the duration of exposure of the cells to the fatty acid and the chain length and degree of unsaturation of the fatty acid. 3. Unsaturated fatty acids suppress production of the immunoregulatory cytokine interleukin-2 by lymphocytes in vitro. 4. Triacylglycerols containing unsaturated fatty acids inhibit lymphocyte proliferation and natural killer cell activity in vitro. 5. Feeding weanling rats diets containing olive oil, evening primrose oil or fish oil results in suppression of lymphocyte proliferation. 6. Preliminary studies indicated that supplementation of the diet of healthy humans with fish oil-containing capsules suppresses lymphocyte proliferation and interleukin-2 production. 7. These effects, along with inhibitory effects upon the functions of other cells involved in the immune response, in particular monocytes and macrophages, indicate that certain unsaturated fatty acid-containing oils (particularly evening primrose oil and fish oil) may be of benefit in the treatment of inflammatory and autoimmune diseases

Effect of a polyunsaturated fatty acid-rich diet on macrophage and lymphocyte metabolism of diabetic rats

Diabetic subjects present high susceptibility to infections but the mechanisms involved are not fully known. Macrophages and lymphocytes utilize glucose and glutamine at high rates and these metabolites are important for the function of these cells. The present study examines the activities of key metabolic enzymes in macrophages and lymphocytes obtained from alloxan-diabetic Wistar rats (10 weeks old, 7 rats each group). Since the enteral diet was enriched with omega-6 polyunsaturated fatty acids (PUFA), the effect of these fatty acids was also investigated in the same animals. Diabetes caused a marked decrease of hexokinase activity (48 per cent ; 274.23 +/- 18.43 vs 143.29 +/- 10.35 units for control vs diabetic rats) in macrophages and of citrate synthase and glucose-6-phosphate dehydrogenase activities (70 per cent ; 321.76 +/- 9.18 vs 96.25 +/- 5.43 units for citrate synthase and 89.43 +/- 2.33 vs 23.13 +/- 1.09 units for G6PDh for control vs diabetic rats) in mesenteric lymph node lymphocytes. A PUFA-rich diet given for 6 weeks enhanced hexokinase activities by 30 per cent (274.23 +/- 18.43 vs 342.48 +/- 15.39, balanced vs PUFA-rich diets for normal and 143.29 +/- 10.35 vs 189.67 +/- 9.57 for diabetic rats) and reduced citrate synthase activities by 43 per cent (30.31 +/- 1.73 vs 17.42 +/- 0.95, balanced vs PUFA-rich diets for normal and 29.34 +/- 1.23 vs 16.73 +/- 1.02 for diabetic rats) in macrophages, and reduced (< 50 per cent ; 59.67 +/- 3.45 vs 48.87 +/- 3.37 for hexokinase and 321.76 +/- 2.33 vs 161.66 +/- 9.97 for citrate synthase, balanced vs PUFA-rich diets) the activities of both enzymes in lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation of monkey small intestinal brush border membrane D-glucose transport by nonesterified fatty acids.

Brush border membranes isolated from monkey intestinal mucosa was found to contain considerable amount of nonesterified fatty acids. Incubation of brush border membranes with fatty acid free albumin selectively removed the free fatty acids more than 80% without altering the level of phospholipids or cholesterol. The sodium dependent D-glucose transport was stimulated by the albumin treatment. Kinetic study showed that albumin treatment did not alter the apparent affinity (Km) of the transporter for glucose whereas the maximal velocity (Vmax) was increased significantly. The sodium dependent D-glucose transport was inhibited by the exogenously added unsaturated fatty acids. Saturated fatty acids and methyl esters of unsaturated fatty acids showed no inhibition. Based on these results, it may be concluded that free fatty acids inhibit the sodium dependent intestinal D-glucose transport either by directly interacting with the transport protein or by abolishing the sodium gradient.

Influencia del contenido de ácidos grasos poliinsaturados Omega 6 dietéticos, en la actividad de enzimas asociadas a la función de la membrana mitocondrial de hígado y placenta de ratas / The effect of dietetic Omega 6 polyunsaturated fatty acids on the enzymes activity associated with the function of the liver mitochondria and placenta in rats

Ratas hembras vírgenes, cepa Wistar, se dividieron en tres grupos de 18 animales cada uno. Un grupo fue alimentado con una dieta que aporta (45% de las calorías como grasa(45g%), otro se alimentó con una dieta baja en grasa (15%), y el tercero sirvió como testigo. Para ambos niveles, alto y bajo, la relación ácidos grasos poliinsaturados a saturados (P/S) se ajustó a 2.0 sustituyendo los ácidos grasos saturados por aceite de maíz (Omega 6). A un grupo control se le ofreció una dieta preparada con 30% (30g%) de las calorías grasas, con una relación P/S de 1.0. Cada grupo consumió sólo una de la dietas desde antes, y durante la preñez. A los 20 días de edad gestacional todas as ratas fueron sacrificadas y se les extrajeron los fetos, placentes, y hígado materno, y se aislaron las membranas mitocondriales de palcentes e hígado. Luego se analizó la composición de los ácidos grasos de los fosfolípidos mitocondriales y la actividad de citocromo-c-oxidasa en la membrana interna, y de NADH citocromo o reductasa insensible a la totenona en la membrana mitocondrial externa. La citocromo-c-oxidasa de vio activada por el aumento de los Omega 6 en los fosfolípidos, originado por la dieta de 45g% P/S2. La acticiad de NADH citocromo-c-reductasa se redujo en el grupo que recibió 15 g%, P/S2, y en ese grupo no se alteró la actividad de citocromo-c-oxidasa en relación al grupo control. El peso fetal del grupo de madrs que consumió 45g% P/S1, experimentó un significativo aumento ponderal en relación a los otros dos grupos. Este estudio indica que dietas análogas en el contenido e grasa y poliinsaturados Omega 6 a a los potencialmente consumidos por humanos, pueden inducir cambios en los constituyentes estructurales de las membranas y en las funciones de las proteínas lípido-dependiente de membrana. Por lo tanto, se postula que un aumento de los poliinsaturados 6 en los fosfolípidos de la membrana mitocondrial favoreció la función celular de los órganos estudiados, reflejándose en el estímulo del crecimiento uterino fetal

Efecto del aumento de los ácidos grasos poliinsaturados (Omega 6) dietéticos en el contenido de glutatión hepático y actividad de gama glutamil transpeptidasa en riñón de ratas / Effect of increase of dietary polyunsaturated fatty acids (Omega 6) on the hepatic glutathione content and gamma-glutamil transpeptidase activity in kidney of rats

Se estudió el efecto de la alimentación de ratas macho, cepa Wistar, desde los 24 a los 52 días de edad, con dietas de frijol deficientes en aminoácidos azufrados o suplementados con 0.3% DL-metionina y con dos concentraciones de aceite de maíz, 2% y 20% (g/Kg dieta), sobre el contenido de glutatión en hígado (GSH) y sobre la actividad de gama glutamil transpeptidasa renal (GGTP) (E.C.2.3.2.2.). Los resultados indicaron que las ratas alimentadas con la dieta de frijol con 2% de aceite de maíz, disminuyeron significativamente el contenido de GSH hepático y la actividad de GGTP renal. La suplementación con 0.3% de metionina y/o el incremento al 20% del aceite de maíz en la dieta, estimularon significativamente el contenido de GSH hepático y la actividad transpeptidásica en el riñon. Se postula que el aumento de los ácidos grasos poliinsaturados estimuló la actividad de GGTP vcomo una manera de aumentar la biodisponibilidad de sustratos para síntese de novo de GSH hepático, necesário para la protecciójn de la formación de hidroperóxidos atribuido al incremento de los ácidos grasos poliinsaturados a nivel celular