Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Eicosanoids”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2005

Functional eicosanoid test and typing (FET) of peripheral blood cells in eicosanoids related diseases.

Monitoring of eicosanoid synthesis in peripheral blood cells has significant potential for improving the diagnosis and therapy of many human diseases. The quantitative relation between concentrations of prostaglandins and leukotrienes is central to the physiologic function of the eicosanoid network. Here we show that this regulation, which we call the functional eicosanoid typing (FET), fluctuates dynamically in individual living blood cells from patients, thereby limiting the accuracy with which concentration circuits of eicosanoids can transfer metabolic information. Using living cells in functional cell testing, we characterised the eicosanoid pattern score (EPS). A novel technique based on binomial errors on lipid mediator partitioning enabled calibration of in vivo biochemical parameters in molecular units. We found that eicosanoid production rates fluctuate over a time scale of about twenty minutes, while intrinsic noise decays rapidly. Thus, biochemical eicosanoid parameters, noise, and slowly varying cellular states together determine the effective FET. These results can form a basis for quantitative modelling of natural eicosanoid circuits in diagnosis of eicosanoid related diseases and design of synthetic ones for the prediction other diseases.

Adult↗
PubMed1999

Eicosanoid production by adult Fasciola hepatica and plasma eicosanoid patterns during fasciolosis in sheep.

Fasciola hepatica infection in sheep is known to cause anaemia, fever and elevated levels of liver enzymes. It was hypothesised that eicosanoids play a role in these pathophysiological changes, so the pattern of plasma eicosanoids during the course of acute and chronic fasciolosis was studied in sheep infected with a single dose of 800 F. hepatica metacercariae. Blood plasma was collected weekly until week 17 p.i. from infected sheep, and from uninfected controls. Adult F. hepatica were then recovered from bile ducts and incubated for production of ES products. Eicosanoids were determined by enzyme immuno-assay in blood plasma, fluke homogenates and ES products after chromatographic purification of the samples. Fever and anaemia were seen from 3 to 12 weeks p.i. and from 8 to 17 weeks p.i., respectively. Onset of fever was accompanied by elevated liver enzyme activities (aspartate amino transferase and gamma glutamyl transferase) in the plasma. In general, the plasma levels of prostaglandin E2 (PGE2), prostaglandin I2 (PGI2) and leukotriene B4 (LTB4) were reduced during the acute and chronic stages of the infection, whereas thromboxane B2 (TXB2) was reduced only at 8 weeks p.i. The TXB2/PGI2 ratio was increased in favour of TXB2 at 3 and 11 weeks p.i. Additionally, TXB2, PGI2, PGE2 and LTB4 were detected both in ES products and in homogenates of F. hepatica. It was concluded that eicosanoid depletion in the plasma is caused by parasite-induced liver damage. The changes in eicosanoid levels are highly correlated to the clinical signs of the disease. Changes in the pattern of host plasma eicosanoids during fasciolosis, as well as parasite-derived eicosanoids, may reflect or contribute to the pathology of the disease.

Acute Disease↗
PubMed1990

Pertussis toxin and H-7 distinguish mechanisms involved in eicosanoid release from lipopolysaccharide-primed macrophages. Eicosanoid release from lipopolysaccharide-primed macrophages.

Release of eicosanoids is an important response of macrophages to inflammation and bacterial infection. At low concentrations, bacterial lipopolysaccharide (1-2 micrograms/ml) fails to stimulate eicosanoid release in resident peritoneal macrophages but primes the macrophages for a greatly enhanced release of eicosanoids on stimulation with the calcium ionophore A23187 (0.1 microM) or with phorbol 12-myristate 13-acetate (50 nM), an activator of protein kinase C. Incubation of macrophages with Bordetella pertussis toxin, prior to priming with lipopolysaccharide, inhibited the release of both cyclooxygenase and lipoxygenase products upon A23187 stimulation. Pertussis toxin treatment of macrophages had no effect on eicosanoid release when the stimulus was phorbol 12-myristate 13-acetate. The presence of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), an effective inhibitor of protein kinase C, during lipopolysaccharide priming and subsequent stimulation significantly inhibited eicosanoid release when phorbol 12-myristate 13-acetate was the stimulus, but did not affect eicosanoid release stimulated by A23187. Based on these results, at least two mechanisms, distinguished by apparent differences in sensitivity to pertussis-toxin-sensitive, guanine-nucleotide-binding proteins and protein kinase C, are involved in eicosanoid secretion by lipopolysaccharide-activated macrophages in response to A23187 and phorbol 12-myristate 13-acetate.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2002

The heart of Ciona intestinalis: eicosanoid-generating capacity and the effects of precursor fatty acids and eicosanoids on heart rate.

Eicosanoids are a group of oxygenated fatty-acid derivatives formed from C20 polyunsaturated fatty acids including arachidonic and eicosapentaenoic acids. In mammals, these compounds have been shown to be key molecules in several physiological processes including regulation of the vascular system. This study determined whether eicosanoids or their precursors are involved in the regulation of heart rate in the sea squirt Ciona intestinalis. Eicosanoid generation by both heart and blood cells was measured. The major lipoxygenase products formed were both derivatives of eicosapentaenoic acid, namely 8- and 12-hydroxyeicosapentaenoic acids (8-HEPE and 12-HEPE). Smaller amounts of 8,15-dihydroxyeicosapentaenoic acid (8,15-diHEPE) were also formed. The cyclo-oxygenase product prostaglandin E was also found in small amounts in the heart. Isolated hearts were exposed either to these fatty acid precursors or to 8-HEPE, 12-HEPE or prostaglandin E3, and the effect on heart rate was recorded. Both eicosapentaenoic and arachidonic acids stimulated the heart rate at concentrations between 50 and 200 micromol l(-1). 12-HEPE (5 micromol l(-1)) and prostaglandin E3 (50 micromoll(-1)) caused a modest increase in heart rate, while 8-HEPE had no significant effects at any of the time periods studied (<or=180 min). Overall, the results show that arachidonic and eicosapentaenoic acids have limited effects on heart rate and only at concentrations unlikely to be routinely liberated in vivo. Similarly, the eicosanoids tested had a minor stimulatory activity on heart rate. The potential mechanisms for this stimulation are discussed. Overall, these results suggest that such compounds are of limited importance in regulating the heart and vascular system of sea squirts.

Animals↗
PubMed1997

Effects of eicosanoids on parameters in isolated rat hepatocytes and isolated rat hepatocyte couplets: protective effects of eicosanoid receptor antagonists.

A number of eicosanoids caused plasma membrane blebbing in hepatocytes and this could be inhibited in a dose-dependent fashion by the receptor antagonists AH6809 and ICI 192605. The pattern of effectiveness of eicosanoids interfering with canalicular vacuole accumulation in hepatocyte couplets differed from that causing blebbing; the two most effective eicosanoids here were PGD2 and PGF2 alpha.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

[Metabolites of arachidonic acid (eicosanoids) in the airways--the role of epithelium in synthesis of eicosanoids].

Arachidonic acid metabolites are potent modulators in physiology and mediators in pathophysiology of airways. They play important role in allergic diseases. There are two main sources of eicosanoids found in nasal and bronchial lavages: airway epithelial cells and influx cells. Authors described spectra of eicosanoids produced by epithelial cells in vitro and compare them with in vivo findings. The review of similarities and differences between arachidonic acid metabolism in human upper and lower airways is also included.

Animals↗
PubMed1987

The ocular pharmacokinetics of eicosanoids and their derivatives. 1. Comparison of ocular eicosanoid penetration and distribution following the topical application of PGF2 alpha, PGF2 alpha-1-methyl ester, and PGF2 alpha-1-isopropyl ester.

These experiments were undertaken to determine whether the increased ocular hypotensive potency of topically applied prostaglandin (PG) PGF2 alpha esters, as compared with that of PGF2 alpha free acid, can be accounted for by increased penetration of the eicosanoid moiety of the esterified PG into the eye. One hour after the topical application of [3H]PGF2 alpha-1-methyl ester (ME) in peanut oil, the 3H activities in the cornea, aqueous humor, and ciliary body of the rabbit eye were 32-, 22-, and 8-fold higher, respectively, than they were following the topical application of [3H]PGF2 alpha free acid. 3H activity during the first 3 hr declined rapidly in the cornea and more slowly in the aqueous humor, but remained essentially constant in the ciliary body for up to 6 hr, declining rapidly only between 6- and 24 hr. 3H activity in eyes that received [3H]PGF2 alpha ME was also several-fold higher in the anterior sclera and iris than in eyes that were treated with [3H]PGF2 alpha free acid, but this difference was much smaller in the conjunctiva. At 1 hr, most of the 3H activity in the aqueous humor was associated with PGF2 alpha, as determined by chromatography, but at 2- and 3 hr other peaks, presumably reflecting metabolites of PGF2 alpha, became apparent. The penetration and intraocular distribution of 3H activity was similar when [3H]PGF2 alpha ME was applied to the eye in normal saline rather than in peanut oil or when the isopropyl rather than the methyl ester of PGF2 alpha was used. These studies indicate that esterification of the carboxyl group of PGF2 alpha greatly enhances the penetration of the PGF2 alpha moiety into the eye and suggests that effective de-esterification of the PGF2 alpha ester occurs in the cornea, resulting in the delivery of PGF2 alpha free acid into the aqueous humor. It is concluded that topically applied PG esters act as pro-drugs and that the increased ocular penetration of these esters may account for the previously reported increase in their ocular hypotensive potency as compared to that of PG free acid or salts.

Administration, Topical↗
PubMed1985

Modification of brain vascular eicosanoids after pharmacological treatment and ischemia in the rat: drugs and brain vascular eicosanoids.

Vascular eicosanoids (E) thromboxane (measured as T X B2) and prostacyclin (measured as 6-keto-PGF1 alpha) may modulate hemodynamic parameters in brain circulation. We have studied (a) the effects of the administration of vasoactive drugs, in the rat, on T X B2 and 6-keto-PGF1 alpha levels and release in brain cortex, and (b) changes of brain vascular E levels during hypoxia and recovery, in the same animal species. Administration of vasoactive drugs (papaverine, dipyridamole, the carbochromene derivative AD6 and nifedipine) to rats resulted in differential effects on endogenous levels and post-decapitation release of both compounds. Reduction of the T X B2/6-keto-PGF1 alpha balance in brain cortex was obtained with papaverine and AD6, whereas nifedipine reduced 6-keto-PGF1 alpha more than T X B2. During hypoxia there was no significant modification of brain vascular E, but during recovery both compounds were decreased. Thus pharmacological treatments during recovery from hypoxia may normalize brain vascular E levels.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Influence of inhibitors of the eicosanoid metabolism, of antagonists of the eicosanoids and of PAF on mortality assayed in three biochemically characterized shock models.

Experiments were carried out to lower the mortality (LD70-90) of rats in ovalbumin-induced anaphylactic (DA) shock and in endotoxin-induced (ET) shock, and of mice after injection of Platelet-activating Factor (PAF shock) comparing the effects of the cyclooxygenase (COX)-inhibitors aspirin (ASA), indomethacin, of the COX-/lipoxygenase (LOX)-inhibitors nordihydroguajaretic acid (NDGA), phenidone and X 86 (analogue of BW 755c), of the inhibitor of thromboxane (TX) synthesis HOE 944, of the TX-antagonist BM 13177, of the PAF-antagonist BN 52021 and of ketotifen. Ketotifen was strongly effective in DA shock, COX- and LOX-inhibitors only slightly. Combined COX- and LOX-inhibitors and BN 52021 showed good effects in the ET shock. Ketotifen was inefficacious. All the used substances influenced the PAF shock. The shock syndromes were biochemically characterized by determination of isocitratedehydrogenase (ICDH) activity, lactate, glucose, haematocrit, numbers of thrombocytes and leucocytes, TXB2 and 6-keto-Prostaglandin(PG)F1 alpha.

Anaphylaxis↗
PubMed1995

Activation of eicosanoid metabolism in human airway epithelial cells by ozonolysis products of membrane fatty acids.

Inhaled ozone can react with a variety of cellular macromolecules within the lung. Recent analyses of the chemistry of ozone reactions with unsaturated fatty acids, which are present in all membranes and in mucus in the airways, indicate that ozonolysis yields one aldehyde and one hydroxyhydroperoxide molecule for each molecule of ozone. The hydroxyhydroperoxide molecule is unstable in aqueous environments, and subsequently yields a second aldehyde and hydrogen peroxide. The structure of common unsaturated fatty acids is such that attack by ozone at the carbon-carbon double bonds will yield 3-, 6-, and 9-carbon saturated and unsaturated aldehydes and hydroxyhydroperoxide. This study examines the effects of ozonolysis products on eicosanoid metabolism in human airway epithelial cells. Eicosanoid biosynthesis is important in a wide array of pathophysiological responses in the airway, and the release of eicosanoids by the epithelial barrier is likely to be significant in diseases induced by environmental factors. Previously, we demonstrated that ozone can increase eicosanoid synthesis from airway epithelial cells exposed in vitro. Human exposures to concentrations of ozone below the current National Ambient Air Quality Standard (0.12 ppm, not to be exceeded for more than one hour once per year) also resulted in increased eicosanoids in bronchoalveolar lavage fluid. To determine whether ozonolysis products could activate eicosanoid release, we exposed human airway epithelial cells to 3-, 6-, and 9-carbon aldehydes, hydroxyhydroperoxides, and hydrogen peroxide. We measured (1) eicosanoid metabolism using high-performance liquid chromatography and radioimmunoassays, and (2) the effects of the aldehydes, hydroxyhydroperoxides, and hydrogen peroxide on cell lysis. Eicosanoid release increased after exposure to aldehyde; release induced by 9-carbon (nonanal) aldehyde was greater than that induced by the 6-carbon (hexanal) or 3-carbon (propanal) aldehydes. Hydroxyhydroperoxides induced greater eicosanoid release than the corresponding aldehydes of equivalent chain length. Again, the longer the aliphatic chain length of the hydroxyhydroperoxide the greater the effect. These effects were noted at concentrations of hydroxyhydroperoxide below those that produce cell lysis, and the time course of the two responses was dissimilar. Because hydroxyhydroperoxides can degrade into an aldehyde and hydrogen peroxide, it is conceivable that the effects observed were attributable to the formation of either hydrogen peroxide or hydrogen peroxide and aldehyde. This mechanism is unlikely, however, because the effects of hydroxyhydroperoxides on eicosanoid release were dependent on chain length, whereas each hydroxyhydroperoxide can produce only one hydrogen peroxide molecule. Although hydrogen peroxide alone also stimulated eicosanoid metabolism, this effect was not augmented when aldehyde and hydrogen peroxide were added together. In addition, the dose of hydroxyhydroperoxide needed to produce an effect (10 to 100 microM) was lower than that of hydrogen peroxide (300 microM). We could not fully evaluate the effects of the unsaturated aldehydes and hydroxyhydroperoxides. Although the 6-carbon and 9-carbon cis-3-aldehydes could be synthesized from the cis-3-alcohols, the resulting aldehydes were not chemically stable. The cis-3-aldehydes were useful for producing the corresponding 1-hydroxy-alkenyl-hydroperoxides of high purity. These results support the method selected for chemical synthesis, but further studies are required to establish proper storage and handling methods before these compounds can be tested in assays of eicosanoid metabolism.

Air Pollutants↗
PubMed1995

Platelet-activating factor stimulates eicosanoid production in cultured feline tracheal epithelial cells.

The effect of platelet-activating factor (PAF) on eicosanoid generation and release in cultured feline tracheal epithelial cells was investigated by measuring a wide range of lipoxygenase and cyclooxygenase pathway products. Subconfluent epithelial cell cultures were stimulated by PAF and eicosanoid production was determined by high performance liquid chromatography (HPLC) of [3H]-labeled arachidonic acid (AA) metabolites and by radioimmunoassay (RIA) following HPLC separation. The HPLC chromatograms revealed that PAF augmented the release of prostaglandin (PG)E2, PGF2 alpha, 12-hydroxyeicosatetraenoic acid (HETE), and AA. Among these eicosanoids, PGE2 predominated under baseline conditions and following PAF exposure. RIAs of the nonradiolabeled HPLC elution corresponding to various eicosanoid standards demonstrated that PAF increased the production of 6-keto-PGF1 alpha, thromboxane B2 (TXB2), PGD2, 5-HETE, and 15-HETE, as well as PGE2, PGF2 alpha, and 12-HETE. The PAF-induced eicosanoid augmentation was dose-dependent and occurred within 1 hour with a prompt decline following termination of PAF exposure. This stimulating effect of PAF on eicosanoid release was blocked by two PAF receptor antagonists, Ro 19-3704 and WEB 2086. The PAF-induced increase in eicosanoid release was similar in magnitude to the increase caused by calcium ionophore (Ca-ionophore) A23187, a potent known stimulus for eicosanoid release. Cells of different culture durations (3 and 6 days) showed similar capacity for eicosanoid production. We conclude that PAF stimulates the production of cyclooxygenase and lipoxygenase pathway products from airway epithelial cells via PAF receptors, and that these epithelium-derived eicosanoids may be responsible for some of the PAF-induced respiratory physiological and pathophysiological effects.

Animals↗
PubMed2005

Gender differences of renal CYP-derived eicosanoid synthesis in rats fed a high-fat diet.

BACKGROUND: Renal cytochrome P450 (CYP)-derived eicosanoids, hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs), and dihydroxyeicosatrienoic acids (DHETs), have been shown to affect renal function and blood pressure (BP). We recently reported that high fat (HF) diet treatment in male rats increases BP and decreases production of these eicosanoids in the kidneys. However, at what level the downregulation of renal eicosanoid synthesis occurs and whether the HF diet has any effects on the regulation of renal eicosanoid synthesis in female rats are not known. The purpose of this study was to determine renal CYP-derived eicosanoid synthesis and its association with BP regulation in HF male and female rats. METHODS: In the first set of experiments, male and female rats were fed the HF or control diet for 10 weeks. In the second set of experiments, male and female rats were fed the HF diet for 10 days. In the third set of experiments, HF-fed and control female rats were treated with 5alpha-dihydrotestosterone for 4 weeks. After treatment, BP, urinary sodium, sodium balance, eicosanoid production, and CYP enzyme expression were determined. RESULTS: An elevation of BP and a decrease of renal cortical eicosanoid production were found in HF male rats, but no BP and eicosanoid production changes were observed in HF female rats. The HF treatment also caused a significant decrease of eicosanoid production and a decrease of CYP4A and 2C23 expression in the proximal tubules of HF male rats. Moreover, the HF diet treatment in male rats caused an increase in cumulative sodium balance and an elevation of BP, whereas no change in cumulative sodium balance and BP was observed in female rats. The treatment of 5alpha-dihydrotestosterone increased BP and 20-HETE production in the renal microvessels, but had no effect on urinary sodium excretion and renal microvessel EET production in both control and HF-fed female rats. CONCLUSIONS: These results demonstrate that there are gender-specific differences in regulation of renal eicosanoid synthesis, sodium balance, and BP caused by HF treatment, and it appears that androgens play some role in upregulation of renal microvessel 20-HETE production in both HF and control female rats.

Androgens↗
PubMed1997

Dietary arachidonic acid increases eicosanoid production in the presence of equal amounts of dietary eicosapentaenoic acid.

Previously, we demonstrated that dietary n-3 PUFA (1.5%, w/w) effectively inhibited the production of eicosanoids derived from tissue arachidonic acid (AA) (Whelan et al., 1991). More recently, we also reported that dietary AA (1.0%, w/w) significantly augmented platelet and macrophage eicosanoid production in vitro (Whelan et al., 1993). This present study was designed to investigate the antithetic relationship of dietary AA and EPA on eicosanoid production in vivo. Forty-nine CD-1 male mice were randomly divided into four dietary groups. Identical diets were supplemented with ethyl esters (1.5%, w/w) of the following fatty acids: oleic acid (OA), AA, EPA or AA + EPA (A + E). After four weeks on diet, peritoneal cells were stimulated in vivo with opsonized zymosan and analyzed for eicosanoid production (PGE2, 6-keto-PGF1a, TXB2, LTE4, LTB4, LTE5 and LTB5). The pooled eicosanoid production in the AA group was 41% and 300% higher compared to the OA (control) and EPA groups, respectively. Pooled eicosanoid production in the EPA group was 47% that of the OA group. When equivalent amounts of AA and EPA (AA + EPA) were included in the diet, the pooled eicosanoid production was 29% and 274% higher compared to the OA and EPA groups, respectively. These data demonstrate that dietary AA (1) enhances eicosanoid production in vivo and (2) abrogates virtually all of the effects observed with dietary EPA when both are included in the diet. The clinical implications of dietary AA as modulated by increased eicosanoid production could be significant, particularly when n-3 PUFA are used to reduce eicosanoid-mediated events.

Analysis of Variance↗