Effects of Total Saponins from Dioscorea Nipponica Makino on Monosodium Urate-Induced M1-Polarized Macrophages through Arachidonic Acid Signaling Pathway: An in vitro Study / 中国结合医学杂志

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.

Mechanism of tryptanthrin in treatment of ulcerative colitis in mice based on serum metabolomics / 中国中药杂志

This study aims to explore the effect of tryptanthrin on potential metabolic biomarkers in the serum of mice with ulcerative colitis(UC) induced by dextran sulfate sodium(DSS) based on liquid chromatography-mass spectrometry(LC-MS) and predict the related metabolic pathways. C57BL/6 mice were randomly assigned into a tryptanthrin group, a sulfasalazine group, a control group, and a model group. The mouse model of UC was established by free drinking of 3% DSS solution for 11 days, and corresponding drugs were adminsitrated at the same time. The signs of mice were observed and the disease activity index(DAI) score was recorded from the first day. Colon tissue samples were collected after the experiment and observed by hematoxylin-eosin(HE) staining. The levels of interleukin-4(IL-4), interleukin-10(IL-10), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-8(IL-8) in the serum were measured by enzyme linked immunosorbent assay(ELISA). The serum samples were collected from 6 mice in each group for widely targeted metabolomics. The metabolic pathways were enriched by MetaboAnalyst 5.0. The results showed that compared with the model group, tryptanthrin treatment decreased the DAI score(P<0.05), alleviated the injury of the colon tissue and the infiltration of inflammatory cells, lowered the levels of proinflammatory cytokines, and elevated the levels of anti-inflammatory cytokines in the serum. The metabolomic analysis revealed 28 differential metabolites which were involved in 3 metabolic pathways including purine metabolism, arachidonic acid metabolism, and tryptophan metabolism. Tryptanthrin may restore the metabolism of the mice with UC induced by DSS to the normal level by regulating the purine metabolism, arachidonic acid metabolism, and tryptophan metabolism. This study employed metabolomics to analyze the mechanism of tryptanthrin in the treatment of UC, providing an experimental basis for the utilization and development of tryptanthrin.

Arachidonic acid metabolism in liver glucose and lipid homeostasis / 生理学报

Arachidonic acid (AA) is an ω-6 polyunsaturated fatty acid, which mainly exists in the cell membrane in the form of phospholipid. Three major enzymatic pathways including the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 monooxygenase (CYP450) pathways are involved in AA metabolism leading to the generation of a variety of lipid mediators such as prostaglandins, leukotrienes, hydroxyeicosatetraenoic acids (HETEs) and epoxyeicoastrienoic acids (EETs). These bioactive AA metabolites play an important role in the regulation of many physiological processes including the maintenance of liver glucose and lipid homeostasis. As the central metabolic organ, the liver is essential in metabolism of carbohydrates, lipids and proteins, and its dysfunction is associated with the pathogenesis of many metabolic diseases such as type 2 diabetes mellitus, dyslipidemia and nonalcoholic fatty liver disease (NAFLD). This article aims to provide an overview of the enzymatic pathways of AA and discuss the role of AA-derived lipid mediators in the regulation of hepatic glucose and lipid metabolism and their associations with the pathogenesis of major metabolic disorders.

Eicosanoids and cancer

Eicosanoids are 20-carbon bioactive lipids derived from the metabolism of polyunsaturated fatty acids, which can modulate various biological processes including cell proliferation, adhesion and migration, angiogenesis, vascular permeability and inflammatory responses. In recent years, studies have shown the importance of eicosanoids in the control of physiological and pathological processes associated with several diseases, including cancer. The polyunsaturated fatty acid predominantly metabolized to generate 2-series eicosanoids is arachidonic acid, which is the major n-6 polyunsaturated fatty acid found in animal fat and in the occidental diet. The three main pathways responsible for metabolizing arachidonic acid and other polyunsaturated fatty acids to generate eicosanoids are the cyclooxygenase, lipoxygenase and P450 epoxygenase pathways. Inflammation plays a decisive role in various stages of tumor development including initiation, promotion, invasion and metastasis. This review will focus on studies that have investigated the role of prostanoids and lipoxygenase-derived eicosanoids in the development and progression of different tumors, highlighting the findings that may provide insights into how these eicosanoids can influence cell proliferation, cell migration and the inflammatory process. A better understanding of the complex role played by eicosanoids in both tumor cells and the tumor microenvironment may provide new markers for diagnostic and prognostic purposes and identify new therapeutic strategies in cancer treatment.

Airborne agricultural particulate matter induces inflammatory cytokine secretion by respiratory epithelial cells: Mechanisms of regulation by eicosanoid lipid signal mediators.

The purpose of this study was to elucidate the mechanism of the airborne poultry dust (particulate matter, PM)-induced respiratory tract inflammation, a common symptom in agricultural respiratory diseases. The study was based on the hypothesis that poultry PM would induce the release of inflammatory cytokine interleukin-8 (IL-8) by respiratory epithelial cells under the upstream regulation by cytosolic phospholipase A2 (cPLA2) activation and subsequent formation of cyclooxygenase (COX)- and lipoxygenase (LOX)-catalyzed arachidonic acid (AA) metabolites (eicosanoids). Human lung epithelial cells (A549) in culture were treated with the poultry PM (0.1-1.0 mg) for different lengths of time, following which PLA2 activity, release of eicosanoids and secretion of IL-8 in cells were determined. Poultry PM (1.0 mg/ml) caused a significant activation of PLA2 in a time-dependent manner (15-60 min), which was significantly attenuated by the calcium-chelating agents, cPLA2-specific inhibitor (AACOCF3) and antioxidant (vitamin C) in A549 cells. Poultry PM also significantly induced the release of COX- and LOX-catalyzed eicosanoids (prostaglandins, thromboxane A2 and leukotrienes B4 and C4) and upstream activation of AA LOX in the cells. Poultry PM also significantly induced release of IL-8 by the cells in a dose- and time-dependent manner, which was significantly attenuated by the calcium chelating agents, antioxidants and COX- and LOX-specific inhibitors. The current study for the first time revealed that the poultry PM-induced IL-8 release from the respiratory epithelial cells was regulated upstream by reactive oxygen species, cPLA2-, COX- and LOX-derived eicosanoid lipid signal mediators.

Nitro-fatty acids: novel anti-inflammatory lipid mediators

Nitro-fatty acids are formed and detected in human plasma, cell membranes, and tissue, modulating metabolic as well as inflammatory signaling pathways. Here we discuss the mechanisms of nitro-fatty acid formation as well as their key chemical and biochemical properties. The electrophilic properties of nitro-fatty acids to activate anti-inflammatory signaling pathways are discussed in detail. A critical issue is the influence of nitroarachidonic acid on prostaglandin endoperoxide H synthases, redirecting arachidonic acid metabolism and signaling. We also analyze in vivo data supporting nitro-fatty acids as promising pharmacological tools to prevent inflammatory diseases.

Metabolism of arachidonic acid in sheep uterus: in vitro studies.

Arachidonic acid (AA) metabolism in the non-pregnant sheep uterus was studied in vitro using conventional chromatographic and HPLC techniques. High expression of both lipoxygenase (LOX) as well as cyclooxygenase (COX) enzymes and their activities was found in the uterine tissues. On incubation of uterine enymes with AA, the LOX products formed were identified as 5-hydroperoxyeicosatetraenoic acid (5-HPETE), 12- and 15-hydroxyeicosatetraenoic acids (12- and 15-HETEs), based on their separation on TLC and HPLC. By employing differential salt precipitation techniques, the LOXs generating products 5-HPETE (5-LOX), 12-HETE and 15-HETE (12- and 15-dual LOX) were isolated. Based on their analysis on TLC, the COX products formed were identified as prostaglandins - PGF2alpha and prostacyclin derivative 6-keto PGF1alpha. The study forms the first report on the comprehensive analysis on the metabolism of AA in sheep uterus in vitro via the LOX and COX pathways.

Molecular Targets of Dietary Polyphenols with Anti-inflammatory Properties

There is persuasive epidemiological and experimental evidence that dietary polyphenols have anti-inflammatory activity. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) have long been used to combat inflammation. Recently, cyclooxygenase (COX) inhibitors have been developed and recommended for treatment of rheumatoid arthritis (RA) and osteoarthritis (OA). However, two COX inhibitors have been withdrawn from the market due to unexpected side effects. Because conventional therapeutic and surgical approaches have not been able to fully control the incidence and outcome of many inflammatory diseases, there is an urgent need to find safer compounds and to develop mechanism-based approaches for the management of these diseases. Polyphenols are found in many dietary plant products, including fruits, vegetables, beverages, herbs, and spices. Several of these compounds have been found to inhibit the inflammation process as well as tumorigenesis in experimental animals; they can also exhibit potent biological properties. In addition, epidemiological studies have indicated that populations who consume foods rich in specific polyphenols have lower incidences of inflammatory disease. This paper provides an overview of the research approaches that can be used to unravel the biology and health effects of polyphenols. Polyphenols have diverse biological effects, however, this review will focus on some of the pivotal molecular targets that directly affect the inflammation process.

Participación del óxido nítrico y los metabolitos del ácido araquidónico vía citocromo P450 en la regulación de la presión arterial / Participation of nitric oxide and arachidonic acid metabolites via cytochrome-p450 in the regulation of arterial blood pressure

El óxido nítrico y los metabolitos del ácido araquidónico vía citocromo P450 contribuyen a la regulación de la presión arterial. La modificación en la síntesis de estos autacoides conduce a hipertensión arterial, sin embargo, se desconoce si existe interacción. Por ello, decidimos estudiar el papel modulador del óxido nítrico y los metabolitos del ácido araquidónico vía citocromo P450, y su interacción, sobre la presión arterial y el contenido renal de citocromo P450. Ratas Wistar macho fueron divididas por grupos: 1) Control, 2) L-NAME (100mg/kg/d v.o.), 3) L-NAME + SnCl2 (10mg/kg/d i.p.) y 4) L-NAME + dexametasona (1mg/kg/d s.c.). Se determinó la presión arterial sistólica y la concentración de nitritos por HPLC en orina y sangre. Los valores de presión arterial sistólica fueron: control 97 ± 7 mmHg, L-NAME 151 ± 4.6 mmHg, L-NAME + SnCl2 133 ± 3 mmHg, y L-NAME + dexametasona 152 ± 4.5 mmHg. Los nitritos en orina fueron: 1) 1.832 ± 0.32, 2) 1.031 ± 0.23, 3) 1.616 ± 0.33 y 4) 1.244 ± 0.33 μmol/mL y en sangre: 1) 0.293 ± 0.06, 2) 0.150 ± 0.05, 3) 0.373 ± 0.13 y 4) 0.373 ± 0.07 μmol/mL. El contenido renal de citocromo P450 fue abatido con el tratamiento de L-NAME + SnCl2, y una respuesta semejante se observó con L-NAME + dexametasona. Tanto óxido nítrico como los metabolitos del ácido araquidónico vía CYP participan en la regulación de la presión arterial. Además, el óxido nítrico contribuye regulando parcialmente el contenido renal del citocromo P450.

Nitric oxide and cytochrome P450 arachidonic acid metabolites participate in blood pressure regulation. The synthesis of these autacoids leads to arterial hypertension. However, it is not known whether there is an interaction between them. Therefore, we studied the modulatory effect of nitric oxide and cytochrome P450-arachidonic acid metabolites, their interaction on blood pressure, and the renal content of cytochrome P450. Male Wistar rats were divided: 1) control, 2) L-NAME (100 mg/kg/d p.o.), 3) L-NAME + SnCl2 (10 mg/kg/d i.p.), and 4) L-NAME + dexamethasone (1 mg/kg/d s.c.). We measured blood pressure and collected urine and blood for nitric oxide measurement. NO2 was quantified by HPLC. Blood pressure was: control, 97 ± 7 mmHg; L-NAME, 151 ± 4.6 mmHg; L-NAME + SnCl2, 133 ± 3 mmHg, and L-NAME + dexamethasone 152 ± 4.5 mmHg. Urine nitrite concentration was: 1) 1.832 ± 0.32, 2) 1.031 ± 0.23, 3) 1.616 ± 0.33, and 4) 1.244 ± 0.33 μmol/mL, while the concentration in blood was: 1) 0.293 ± 0.06, 2) 0.150 ± 0.05, 3) 0.373 ± 0.13, and 4) 0.373 ± 0.07 μmol/ mL. L-NAME + SnCl2 decreased cytochrome P450 renal content, and L-NAME + dexamethasone showed a similar response. In conclusion, both, nitric oxide and CYP-arachidonic acid metabolites play a role in the regulation of blood pressure. Nitric oxide also partially regulates renal cytochrome P450 content. (Arch Cardiol Mex 2003; 73:98-104).

Nitric oxide production and arachidonic acid metabolism in platelet membranes of coronary heart disease patients with and without diabetes

Aim: To evaluate the levels of nitrite [NO-2] and nitrate [NO-3] ions and the incorporation of [3H]arachidonic acid [AA] into phospholipids of platelet membranes from coronary artery disease [CAD] patients with and without diabetes [NIDDM]. Subjects and Eighteen CAD patients [group A], 18 CAD patients with NIDDM [group B], and 20 healthy controls [group C] without dyslipidemia, peripheral vascular disease and hypertension were included in the study. The groups were matched for age, sex and body mass index. The diagnosis of CAD was confirmed by coronary angiography. The nitric oxide end products [NOx], NO-2 plus NO-3 ions in platelet membranes, were determined using a spectrophotometric method based on the Griess reaction. The turnover of phospholipids was evaluated by incorporation of [3H]AA into platelet membrane phospholipids. A significantly smaller amount of NOx ions was in the platelet membrane of groups A [40 +/- 8 micro mol/l] and B [29 +/- 10 micro mol/l] than C [57 +/- 6 micro mol/l], p < 0.001. Conversely a significantly greater amount of [3H]AA was incorporated into platelet phospholipids of group B patients [5,123 +/- 1,637 dpm/mg] than groups A [3,159 +/- 1,253 dpm/mg; p < 0.002] and C [1,621 +/- 417 dpm/mg]. An inverse correlation between [3H]AA incorporation and NOx levels was established: r = -0.76 [p < 0.05, n = 36] in CAD patients. Conclusions: Diabetes in CAD patients decreased the ability to produce platelet-derived NO and affects AA metabolism. This may result in higher platelet sensitivity to aggregating stimuli

Efeito de flavonóides no metabolismo do ácido araquidônico / Effect of flavonoids on the arachidonic acid metabolism

Os produtos da açäo das enzimas ciclooxigenase e lipoxigenase sobre o ácido araquidônico säo prostaglandinas, tromboxanos e leucotrienos, também denominados eicosanóides. Tais compostos säo agentes homeostáticos, envolvidos na manutençäo da integridade dos sistemas inflamatório, cardiovascular e renal. Vários pesquisadores têm demonstrado que flavonóides apresentam inúmeras propriedades farmacológicas, entre elas atividade antiinflamatória e hipocolesterolêmica, reduzindo, assim, o risco de doenças cardiovasculares e um dos principais mecanismos de açäo propostos é a inibiçäo das enzimas, envolvidas no metabolismo final do araquidonato. Este trabalho mostra uma revisäo sobre o metabolismo do ácido araquidônico e os efeitos farmacológicos de flavonóides nessa rota metabólica

Importancia de las prostaglandinas en la amibiasis hepática / The importance of prostaglandins in hepatic amebiasis

Las prostaglandinas son importantes mediadores inflamatorios, pero también desempeñan un papel importante como reguladoras de las funciones de los linfocitos y los macrófagos. La inoculación por vía intrahepática o intraportal de trofozoitos viables de Entamoeba histolytica en hámsteres se caracteriza por una rápida respuesta inflamatoria aguda, en la cual los trofozoitos amibianos se ven rodeados sucesivamente por leucocitos polimorfonucleares, linfocitos y macrófagos. La incapacidad de estas células para contrarrestar la invasión amibiana ha sido demostrada en varios estudios. La prostaglandina E2 (PGE2) tiene potentes efectos sobre las células de la respuesta inmune; su participación durante la formación del absceso hepático se reportó recientemente. En este artículo hacemos una revisión de los hallazgos de los últimos años en relación con el estudio de los mediadores bioquímicos de la inflamación durante la infección con E. histolytica, y su posible participación en el establecimiento de la respuesta inmune en el huésped.

Prostaglandins are important mediators of inflammation; they also play a role in the regulation of both lymphocyte and macrophage functions. Hamster's liver lesions resulting from intraportal or intrahepatic inoculation of living Entamoeba histolytica trophozoites are characterized by an acute inflammatory response, where trophozoites are successively surrounded by polymorphonuclear leukocytes, lymphocytes, and macrophages. Incapability of these cells to counteract amebic invasion has been demonstrated in some studies. Prostaglandin E2 (PGE2) has potent effects on immune cells; its participation in amebic liver abscess has been reported recently. This paper presents a review of recent discoveries on biochemical mediators produced during inflammation due to Entamoeba histolytica infection, and their possible role in establishing the host's immune response.

Aspirina, ticlopidina ou clopidogrel? / Aspirin, ticlopidine or clopidogrel?

Os quadros isquêmicos miocárdicos agudos iniciam-se a partir da formação do trombo sobre a placa aterosclerótica. Em circunstâncias em que ocorre lesão endotelial - ruptura da placa - , a adesão, a ativação e a agregação das plaquetas desencadeiam o processo de formação do trombo. O objetivo da terapêutica antiplaquetária nas síndromes isquêmicas agudas é modificar as funções da plaqueta no sentido de inibir a formação e o desenvolvimento do trombo arterial sem prejuízo da hemostasia. Entre as substâncias antiplaquetárias destaca-se a aspirina, que atua impedindo a formação da tromboxane A2, que é importante no processo de formação do trombo. A aspirina, comprovadamente, trouxe grande impacto na modificação da evolução clínica dos pacientes com angina instável ou infarto agudo do miocárdio. Os derivados tienopiridínicos, ticlopidina e clopidogrel, agem inibindo a ação do difosfato de adenosina e, portanto, impedindo a ativação plaquetária. Importantes estudos clínicos demonstraram que esses fármacos apresentam benefícios comparáveis aos da aspirina. São, portanto, recomendados na impossibilidade de se utilizar esta última. Os dados dos estudos que avaliam os efeitos da associação dos tienopiridínicos com a aspirina demonstram as vantagens de se atuar concomitantemente em mecanismos diferentes da ativação das plaquetas para a prevenção de eventos isquêmicos miocárdicos, tanto no contexto dos procedimentos invasivos como no tratamento clínico da angina instável.

Fatty acid patterns in gastric mucosa of stomach cancer patients

omega6 and omega3 fatty acids are important cellular components and known to be involved in disease processes. However, few studies have focused on mucosa fatty acid in human gastric cancer. The purpose of this study was to investigate how fatty acid patterns of mucosa are altered in gastric cancer. Fatty acids were analyzed by gas chromatography and their relative compositions (%) were determined and evaluated both in mucosa total-fatty acids and in phospholipid-fatty acids in paired cancerous and non-cancerous gastric cancer tissues (n = 18). The level of arachidonic acid (20:4omega6, AA) appeared significantly higher both in phospholipid-fatty acids (p < 0.05) and in total-fatty acids (p < 0.001) in cancerous mucosa compared to non-cancerous mucosa. The omega6/omega3 fatty acid ratio of phospholipid-fatty acids was also significantly higher in cancerous mucosa. The higher level of AA in cancerous tissue can be partially explained by the higher ratio of 20:4omega 6/20:3omega6 (desaturation index) and the lower ratio of 22:4omega6/20:4 omega6 (elongation index). The change in the relative composition of arachidonic acid may influence the production of prostaglandins and related metabolites, which regulate cell differentiation and proliferation. The findings of this study with respect to fatty acid changes, especially in terms of arachidonic acid metabolism, may be of relevance in the understanding of the roles of specific fatty acids and possibly of eicosanoids in gastric cancer.

Antiinflamatorios no esteroideos (Parte I): del ácido acetilsalicílico (1899) a los inhibidores selectivos de COX-2 (1999) / Non steroidal antiinflamatory drugs (Part I): from acetylsalycilic acid (1899) to selective COX-2 inhibitors (1999)

Los antiinflamatorios no esteroideos (AINE) son la piedra angular para el manejo de la gran mayoría de las enfermedades reumáticas y a la vez representan una de las clases terapéuticas de mayor prescripción a nivel mundial para una gran variedad de situaciones clínicas que se acompañan de dolor e inflamación. Si bien hoy en día su eficacia está fuera de toda duda, no se puede pasar por alto la enorme toxicidad de los AINE, misma que prácticamente ha alcanzado proporciones "epidémicas" y es responsable de una gran número de muertes, muchas de ellas prematuras, relacionadas con complicaciones de úlcera péptica como sangrado y perforación. Se han identificado claramente factores que predisponen - casi de manera exponencial - al desarrollo de complicaciones a nivel gastrointestinal y de otros órganos y sistemas. Si bien se han demostrado la capacidad del misoprostol y omeprazol para prevenir y disminuir el impacto de la toxicidad gastrointestinal de los AINE, muy posiblemente la solución real a este problema solo se logrará con la disponibilidad de AINE mas seguros a nivel gastrointestinal como los inhibidores selectivos de COX-2. Aunque la mayoría de los estudios coinciden en que los efectos colaterales de los inhibidores selectivos de COX-2 generalmente son semejantes a los observados con placebo, aún deberá de pasar algún tiempo para poder definir plenamente la seguridad a largo plazo de esta nueva generación de antiinflamatorios.

Calyculin A modulates activation of the NADPH-oxidase in Me2SO-differentiated HL-60 cells

Human promyelocytic leukemia cells (HL-60) have been used as a model system in which to study the effects of protein phosphatase inhibitors on NADPH-oxidase activation. Since O2- is generated by NADPH-oxidase, we examined the effect of calyculin A pretreatment on oxidase activation in response to various agonists. When Me2SO-differentiated HL-60 cells were treated with calyculin A prior to the addition of phorbol 12-myristate 13-acetate (PMA), O2- production was inhibited; however, calyculin A enhanced O2- production by N-formyl-methionyl-leucyl-phenylalanine (FMLP). The decreased O2- production seen with calyculin A pretreatment followed by PMA may be due to diminished translocation of the p47-phox and p67-phox, cytosolic components of the oxidase, and inhibition of arachidonic acid release. Interestingly calyculin A pretreatment followed by either agonist significantly enhanced mitogen-activated-protein kinase (MAPK) activity. The differential effects of pretreatment with calyculin A on subsequent oxidase stimulation elicited by FMLP or PMA provide further evidence for substantial heterogeneity in the activation of the respiratory burst.

Effects of lipoproteins on cyclo-oxygenase and lipoxygenase pathways in human platelets

The products of arachidonic acid [AA] metabolism in platelets play an important role in platelet shape change, adhesion and aggregation which may participate in the pathogenesis of ischemic heart disease and thrombosis. Since lipoproteins are also involved in the pathogenesis of thrombo-embolic disorders, the effect of human lipoproteins [HDL, LDL, VLDL] on AA metabolism in human platelets was investigated. Lipoproteins were separated by density gradient zonal ultracentrifugation. The effects of lipoproteins on production of AA metabolites in human platelets i.e., thromboxane A2 [TXA2] and hydroxy-eicosatetraenoic acids [HETEs] were examined using radiometric thin layer chromatography coupled with automated data integrator system. In human platelets, HDL inhibited 12-HETE and TXA2 formation in a concentration-dependent manner. LDL had a strong inhibitory effect on TXA2 production and a weak inhibitory effect on 12-HETE production. VLDL had no effect on platelet AA metabolism. These findings point to a new facet of lipoproteins action and suggest that lipoproteins may have a physiological role in the regulation of AA metabolism in platelets

Mediadores derivados da cadeia do ácido aracdônico e sua relaçäo com as doenças periodontais / Derivates of the arachidonic acid and their relation to periodontal disease

Os produtos do metabolismo do ácido aracdônico, segundo a literatura, contribuem no processo inflamatório das doenças periodontais. Um dos produtos derivados da ciclooxigenase e do ácido aracdônico, a prostaglandina E2, pode ser, no futuro, um possível marcador de doença. A constataçäo da presença de níveis elevados de prostaglandina E2 nos tecidos adjacentes à bolsa periodontal e no fluido do sulco gengival de sítios doentes estimulou estudos de avaliaçäo desse metabólito em amostras do fluido. Uma correlaçäo positiva com perda óssea periodontal foi determinada por diversos autores. Esse fato levou ao estudo de antiinflamatórios näo esteróides com capacidade de inibir o metabolismo do ácido aracdônico, indicando a possibilidade do uso dessa droga como auxiliar na terapêutica periodontal