Arachidonic Acid In Cell Membranes Research Articles

Cod Liver Oil Supplementation Effects on 2,3‐ Diphosphoglyceric Acid Blood Levels in Atherogenic Rabbits

2,3 Diphosphoglyceric Acid (2,3‐DPG) promotes release of oxygen from hemoglobin in the blood of higher animals, and may reduce atherogenic plaque development in hyercholesterolemic rabbits. Eicosapentanoic acid (EPA) converts arachidonic acid in cell membranes to Prostaglandin I‐3, which inhibits platelet aggregation and reduces blood clot formation. Atherogenesis and increased blood vascular fibrin clot formation can be induced in rabbits by feeding a diet containing 2% cholesterol for a month. Blood clot formation at the intimal surface in the aorta reduces oxygen availability which leads to lipid infiltration and plaque development. The effect of feeding atherogenic rabbits cod liver oil (CLO) containing 10% EPA, was studied here to determine its effect on blood levels of 2,3 Diphosphoglyceric Acid (2,3‐DPG).For a month, 12 white, New Zealand strain, male rabbits were fed atherogenic diet (AD) of 92% Purina Rabbit Chow(PRC), 6% Corn Oil and 2% Cholesterol. In the next 8 weeks, 6 rabbits were fed a control diet (CD) of PRC and 6 continued to be fed AD. Half of the CD and AD groups receied 0.8ml CLO daily. Blood 2,3‐DPG means after 2 weeks were: 1.51ug/ml in (CD ) vs 1.75 in the (CD + CLO) and 1.39 in ( AD) vs 1.81 in ( AD+ CLO) animals. After 8 weeks the means were 2.12 (CD) vs 2.35 (CD+CLO), and 1.51 (AD) vs 1.82 (AD+ CLO). The ( CD+CLO ) animals had the highest 2,3 DPG levels of all groups and the least aortal lipid infiltration. (AD+CLO) 2,3 DPG levels were significantly higher than in (AD) controls and they had lower lipid infiltration in their aortae. Blood plasma cholesterol levels in the AD groups were significantly lower in the ( AD+CLO ) vs the (AD) control rabbits.

Montelukast in Allergic Rhinitis: A Review

Leukotriene inhibitors are the first new class of medications for the treatment of persistent asthma that have been approved by the U.S food and drug Administration in more than two decades. They also have been approved for the treatment of Allergic Rhinitis. Leukotrienes are inflammatory mediators that are known as the slow-reacting substance of anaphylaxis. Synthesis of these mediators results from the cleavage of arachidonic acid in cell membranes, exert their biologic effect by binding and activating specific adaptors. This occurs in a series of events that lead to their important role in the Allergic Rhinitis. Because agents lead to the production of symptoms, the use of leukotriene inhibitors, particularly montelukast seems appropriate. These classes of drug can block the binding of leukotrienes to CysLT1 receptors and can also result in the prevention of leukotriene activity. Montelukast is the most commonly used inhibitor of the leukotriene pathway because of its ease of use , good safety profile, and once-daily regimen. We conduct a systematic review of studies that have evaluated montelikast in the treatment of Allergic Rhinitis. This review focuses on the pathophysiology and effect of montelukast in Allergic Rhinitis. The purpose of this paper is to provide an overview of the accumulation data concerning these agents in treating Allergic Rhinitis. Montelukast provides an effective and well tolerated oral treatment for Allergic Rhinitis.DOI: http://dx.doi.org/10.3329/medtoday.v24i2.15012 Medicine Today 2012 Vol.24(2): 75-78

Eco‐physiological repercussions of dietary arachidonic acid in cell membranes of active tissues of the Gray whale

AbstractThe radiation of the mammalian land species that became the baleen whales happened about 27–34 Mya. Mammals require omega 6 fatty acids for reproduction. With this long exposure to the omega 3‐rich marine food chain, the Gray whale (Eschrichtius robustus) might be expected to have lost its requirement for omega 6 fatty acids. We report an unexpectedly high content of omega 6 arachidonic acid (ArA) in the Gray whale liver and muscle lipids. This whale migrates 10,000 km from the cold polar, omega 3 oil‐rich food chain to that of the breeding lagoons of the tropical waters. The food web of tropical waters is a source of omega 6 fatty acids, which are hardly present in the cold polar food web. We suggest the reason for this longest of migrations from cold to warm waters is to meet the requirement for omega 6 fatty acids for mammalian reproduction and brain growth. This extreme conservation of omega 6 fatty acids in Gray whale biology has critical implications for mammalian biology and especially for whale conservation.

Trans-Arachidonic acids induce a heme oxygenase-dependent vasorelaxation of cerebral microvasculature

Nitrative stress is an important regulator of vascular tone. We have recently described that trans-arachidonic acids ( TAA) are major products of NO 2 ·–mediated isomerization of arachidonic acid in cell membranes and that nitrative stress increases TAA levels leading to neural microvascular degeneration. In the present study, we explored whether TAA exert acute effects on neuromicrovascular tone and investigated potential mechanisms thereof. TAA induced an endothelium-dependent vasorelaxation of rat brain pial microvasculature. This vasorelaxation was independent of nitric oxide, prostanoids, lipoxygenase products, and CYP 450 metabolite trans-hydroxyeicosatetraenoic acids. However, inhibition of heme oxygenase (using zinc protoporphyrin IX) and of dependent soluble guanylate cyclase (sGC; using ODQ) significantly diminished (by ∼ 70%) the TAA-induced vasorelaxation. Consistent with these findings, TAA stimulated heme oxygenase (HO)-2-dependent bilirubin (using siRNA HO-2) and cGMP formation, and the HO product carbon monoxide (using CO-releasing CORM-2) reproduced the sGC-dependent cGMP formation and vasorelaxation. Further exploration revealed that TAA-induced vasorelaxation and bilirubin formation (HO activation) were nearly abrogated by large-conductance calcium-dependent potassium channels (BK Ca) (using TEA and iberiotoxin). Opening of BK Ca with the selective activator NS1619 induced a concentration-dependent vasorelaxation, which was inhibited by HO and sGC inhibitors. Coimmunoprecipitation suggested a molecular complex interaction between BK Ca and HO-2 (but not HO-1). Collectively, these findings identify new properties of TAA, specifically cerebral vasorelaxation through interactive activation of BK Ca with HO-2 and, in turn, sGC. Our findings provide new insights into the characterization of nitrative stress-derived TAA products, by showing they can act as acute mediators of nitrative stress on neurovascular tone.

Polyunsaturated fatty acids and inflammation

The n-6 polyunsaturated fatty acid arachidonic acid gives rise to the eicosanoid family of mediators (prostaglandins, thromboxanes, leukotrienes and related metabolites). These have inflammatory actions in their own right and also regulate the production of other mediators including inflammatory cytokines. Consumption of long chain n-3 polyunsaturated fatty acids decreases the amount of arachidonic acid in cell membranes and so available for eicosanoid production. Thus, n-3 polyunsaturated fatty acids decrease production of arachidonic acid-derived eicosanoids. These fatty acids also decrease the production of the classic inflammatory cytokines tumour necrosis factor, interleukin-1, and interleukin-6 and the expression of adhesion molecules involved in inflammatory interactions between leukocytes and endothelial cells. These latter effects may occur by eicosanoid-independent mechanisms including modulation of the activation of transcription factors involved in inflammatory processes. The anti-inflammatory actions of long chain n-3 fatty acid-induced effects may be of therapeutic use in conditions with an acute or chronic inflammatory component.

Polyunsaturated fatty acids and inflammation

The n-6 polyunsaturated fatty acid, arachidonic acid, is a precursor of prostaglandins, leukotrienes and related compounds that have important roles as mediators and regulators of inflammation. Consuming increased amounts of long chain n-3 polyunsaturated fatty acids (found in oily fish and fish oils) results in a partial replacement of the arachidonic acid in cell membranes by eicosapentaenoic and docosahexaenoic acids. This leads to decreased production of arachidonic acid-derived mediators. This alone is a potentially beneficial anti-inflammatory effect of n-3 fatty acids. However, n-3 fatty acids have a number of other effects that might occur downstream of altered eicosanoid production or are independent of this. For example, they result in suppressed production of pro-inflammatory cytokines and can modulate adhesion molecule expression. These effects occur at the level of altered gene expression.

Fatty acid intake and incident nephrolithiasis

Elevated levels of arachidonic acid in cell membranes may promote the hypercalciuria and hyperoxaluria that are characteristic of idiopathic calcium nephrolithiasis. The intake of n-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may decrease the arachidonic acid content of cell membranes and reduce urinary excretion of calcium and oxalate. It has been proposed that greater intake of EPA and DHA (through dietary sources or fish oil supplementation) may reduce the risk for kidney stone formation. After excluding subjects with a prior history of kidney stones, we prospectively examined the relation between fatty acid intake (including fish oil supplements) and incident symptomatic kidney stones in 3 large cohorts: the Health Professionals Follow-Up Study (N = 46,043), the Nurses' Health Study I (NHS I; N = 92,079), and the Nurses' Health Study II (N = 96,304). Self-administered food-frequency questionnaires were used to assess fatty acid intake every 4 years. Cox proportional hazards regression was used to adjust simultaneously for a variety of risk factors. We documented 3,956 incident kidney stones during a combined 36 years of follow-up. After adjustment for intake of other dietary factors, no association was detected between the intake of arachidonic acid or linoleic acid (a metabolic precursor to arachidonic acid) and the risk for incident kidney stones. Older women (NHS I) in the highest quintile of EPA and DHA intake had a multivariate relative risk of 1.28 (95% confidence interval, 1.04 to 1.56; P for trend = 0.04) of stone formation compared with women in the lowest quintile. However, this relation was not observed in the other 2 cohorts. Fatty acid intake is not consistently associated with the development of kidney stones. Greater levels of arachidonic and linoleic acid intake do not increase the risk for developing a kidney stone, and greater intake of n-3 fatty acids does not reduce the risk.

A review of montelukast in the treatment of asthma and allergic rhinitis

Montelukast sodium (Singulair®, Merck) is a selective and orally-active leukotriene-receptor antagonist (LTRA) that inhibits the cysteinyl leukotriene 1 (CysLT1) receptor. Montelukast is an effective and well-tolerated preventative treatment for asthma and allergic rhinitis in adults and children. The upper and lower airway show similar inflammatory responses to allergen challenge. Leukotrienes are inflammatory mediators that are known as the slow-reacting substance of anaphylaxis produced by a number of cell types including mast cells, eosinophils, basophils, macrophages and monocytes. Synthesis of these mediators results from the cleavage of arachidonic acid in cell membranes and they exert their biological effects by binding and activating specific receptors. This occurs in a series of events that lead to contraction of the human airway smooth muscle, chemotaxis and increased vascular permeability. These effects have led to their important role in the diseases of asthma and allergic rhinitis. As these agents lead to the production of symptoms in patients that are asthmatic or allergic, the use of LTRAs, particularly montelukast, may seem appropriate. Clinical trials have shown that montelukast is effective and safe in the treatment of patients with asthma, allergic rhinitis or both diseases.

A review of montelukast in the treatment of asthma and allergic rhinitis

Montelukast sodium (Singulair®, Merck) is a selective and orally-active leukotriene-receptor antagonist (LTRA) that inhibits the cysteinyl leukotriene 1 (CysLT1) receptor. Montelukast is an effective and well-tolerated preventative treatment for asthma and allergic rhinitis in adults and children. The upper and lower airway show similar inflammatory responses to allergen challenge. Leukotrienes are inflammatory mediators that are known as the slow-reacting substance of anaphylaxis produced by a number of cell types including mast cells, eosinophils, basophils, macrophages and monocytes. Synthesis of these mediators results from the cleavage of arachidonic acid in cell membranes and they exert their biological effects by binding and activating specific receptors. This occurs in a series of events that lead to contraction of the human airway smooth muscle, chemotaxis and increased vascular permeability. These effects have led to their important role in the diseases of asthma and allergic rhinitis. As these agents lead to the production of symptoms in patients that are asthmatic or allergic, the use of LTRAs, particularly montelukast, may seem appropriate. Clinical trials have shown that montelukast is effective and safe in the treatment of patients with asthma, allergic rhinitis or both diseases.

Polyunsaturated fatty acids and inflammation

The n-6 polyunsaturated fatty acid arachidonic acid gives rise to the eicosanoid family of inflammatory mediators (prostaglandins, leukotrienes and related metabolites) and through these regulates the activities of inflammatory cells, the production of cytokines and the various balances within the immune system. Fish oil and oily fish are good sources of long chain n-3 polyunsaturated fatty acids. Consumption of these fatty acids decreases the amount of arachidonic acid in cell membranes and so available for eicosanoid production. Thus, n-3 polyunsaturated fatty acids act as arachidonic acid antagonists. Components of both natural and acquired immunity, including the production of key inflammatory cytokines, can be affected by n-3 polyunsaturated fatty acids. Although some of the effects of n-3 fatty acids may be brought about by modulation of the amount and types of eicosanoids made, it is possible that these fatty acids might elicit some of their effects by eicosanoid-independent mechanisms. Such n-3 fatty acid-induced effects may be of use as a therapy for acute and chronic inflammation, and for disorders that involve an inappropriately-activated immune response.

The role of leukotriene inhibitors in patients with paranasal sinus disease.

Leukotrienes are inflammatory mediators that are known as the slow-reacting substance of anaphylaxis produced by a number of cell types including mast cells, eosinophils, basophils, macrophages, and monocytes. Synthesis of these mediators results from the cleavage of arachidonic acid in cell membranes, and they exert their biologic effects by binding and activating specific adaptors. This occurs in a series of events that lead to contraction of the human airway smooth muscle, chemotaxis, and increased vascular permeability. These effects have led to their important role in the diseases of asthma, allergic rhinitis, and possible paranasal sinusitis with the formation of nasal polyps. Because these agents lead to the production of symptoms in patients that are asthmatic, the use of leukotriene enzyme inhibitors, particularly montelukast, and zafirlukasts seem appropriate. These classes of drugs can block the binding of leukotrienes to CysLT(1) receptors. Zileuton is a 5-lipoxygenase inhibitor that prevents the formation of leukotrienes and can also result in the prevention of leukotriene activity. Demonstrated efficacy in these patients in a number of studies has also suggested their role in inhibiting nasal symptoms in asthmatic patients. In addition, it has been suggested by serendipitous observations that many of the aspirin-intolerant patients have nasal polyps and that treatment with the leukotriene inhibitors has resulted in improvement and resolution of the polyps. Therefore, these agents may also play a role in patients afflicted with chronic sinusitis with concomitant nasal polyposis. These papers are discussed in detail because this form of therapy may represent a novel way to treat patients with this malady in addition to or in lieu of surgical treatment and steroid therapy.

N-3 polyunsaturated fatty acids and inflammation: from molecular biology to the clinic.

The immune system is involved in host defense against infectious agents, tumor cells, and environmental insults. Inflammation is an important component of the early immunologic response. Inappropriate or dysfunctional immune responses underlie acute and chronic inflammatory diseases. The n−6 PUFA arachidonic acid (AA) is the precursor of prostaglandins, leukotrienes, and related compounds that have important roles in inflammation and in the regulation of immunity. Feeding fish oil results in partial replacement of AA in cell membranes by EPA. This leads to decreased production of AA-derived mediators, through several mechanisms, including decreased availability of AA, competition for cyclooxygenase (COX) and lipoxygenase (LOX) enzymes, and decreased expression of COX-2 and 5-LOX. This alone is a potentially beneficial anti-inflammatory effect of n−3 FA. However, n−3 FA have a number of other effects that might occur down-stream of altered eicosanoid production or might be independent of this effect. For example, dietary fish oil results in suppressed production of proinflammatory cytokines and can modulate adhesion molecule expression. These effects occur at the level of altered gene expression. Fish oil feeding has been shown to ameliorate the symptoms of some animal models of autoimmune disease and to protect against the effects of endotoxin. Clinical studies have reported that oral fish oil supplementation has beneficial effects in rheumatoid arthritis and among some asthmatics, supporting the idea that the n−3 FA in fish oil are anti-inflammatory. There are indications that the inclusion of fish oil in enteral and parenteral formulae is beneficial to patients.

Polyunsaturated fatty acids, inflammation and immunity.

Consumption of n-6 polyunsaturated fatty acids greatly exceeds that of n-3 polyunsaturated fatty acids. The n-6 polyunsaturated fatty acid arachidonic gives rise to the eicosanoid family of inflammatory mediators (prostaglandins, leukotrienes and related metabolites) and through these regulates the activities of inflammatory cells, the production of cytokines and the various balances within the immune system. Fish oil and oily fish are good sources of long chain n-3 polyunsaturated fatty acids. Consumption of these fatty acids decreases the amount of arachidonic acid in cell membranes and so available for eicosanoid production. Thus, n-3 polyunsaturated fatty acids act as arachidonic acid antagonists. Components of both natural and acquired immunity, including the production of key inflammatory cytokines, can be affected by n-3 polyunsaturated fatty acids. Although some of the effects of n-3 fatty acids may be brought about by modulation of the amount and types of eicosanoids made, it is possible that these fatty acids might elicit some of their effects by eicosanoid-independent mechanisms. Such n-3 fatty acid-induced effects may be of use as a therapy for acute and chronic inflammation, and for disorders which involve an inappropriately activated immune response.

The role of leukotriene inhibitors in allergic rhinitis and paranasal sinusitis.

Leukotrienes are inflammatory mediators that are known as the slow-reacting substance of anaphylaxis produced by a number of cell types, including mast cells, eosinophils, basophils, macrophages, and monocytes. Synthesis of these meditators in the text result from the cleavage of arachidonic acid in cell membranes, and exert their biologic effects by binding and activating specific adaptors. This occurs in a serious of events that lead to contraction of the human airway smooth muscle, chemotaxis, and increased vascular permeability. These effects have lead to their important role in the diseases of asthma, allergic rhinitis, and possible paranasal sinusitis with the formation of nasal polyps. Since these agents lead to the production of symptoms in patients who are asthmatic, the use of leukotriene enzyme inhibitors, particularly montelukast, zafirlukasts seem appropriate.

Polyunsaturated fatty acids, inflammation, and immunity.

The fatty acid composition of inflammatory and immune cells is sensitive to change according to the fatty acid composition of the diet. In particular, the proportion of different types of polyunsaturated fatty acids (PUFA) in these cells is readily changed, and this provides a link between dietary PUFA intake, inflammation, and immunity. The n-6 PUFA arachidonic acid (AA) is the precursor of prostaglandins, leukotrienes, and related compounds, which have important roles in inflammation and in the regulation of immunity. Fish oil contains the n-3 PUFA eicosapentaenoic acid (EPA). Feeding fish oil results in partial replacement of AA in cell membranes by EPA. This leads to decreased production of AA-derived mediators. In addition, EPA is a substrate for cyclooxygenase and lipoxygenase and gives rise to mediators that often have different biological actions or potencies than those formed from AA. Animal studies have shown that dietary fish oil results in altered lymphocyte function and in suppressed production of proinflammatory cytokines by macrophages. Supplementation of the diet of healthy human volunteers with fish oil-derived n-3 PUFA results in decreased monocyte and neutrophil chemotaxis and decreased production of proinflammatory cytokines. Fish oil feeding has been shown to ameliorate the symptoms of some animal models of autoimmune disease. Clinical studies have reported that fish oil supplementation has beneficial effects in rheumatoid arthritis, inflammatory bowel disease, and among some asthmatics, supporting the idea that the n-3 PUFA in fish oil are anti-inflammatory and immunomodulatory.

(E)-4-Hydroxy-2-Nonenal May be Involved in the Pathogenesis of Parkinson’s Disease

( E)-4-Hydroxy-2-nonenal (HNE) is a toxic end-product of the free radical-stimulated peroxidation of phospholoipid-bound arachidonic acid in cell membranes. There is a growing body of evidence to suggest that free radicals may play an important role in the pathology of Parkinson’s disease. HNE is highly electrophilic and is conjugated to reduced glutathione (GSH) by glutathione S-transferase. The depletion of GSH in the substantia nigra of Parkinson’s patients and in the brainstem of mice treated with the neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) prompted this study on the concentrations of HNE in the cerebrospinal fluid (CSF) and plasma of Parkinson’s patients and the brainstem of mice treated with MPTP. HNE was identified and quantitated by a highly specific and sensitive method based on the gas chromatography-negative-ion chemical ionisation mass spectrometry of the O-pentafluorobenzyl oxime derivative using 9 D 3-4-hydroxy-2-nonenal as an internal standard. The mean concentration of HNE in the CSF of patients with Parkinson’s disease was 1.47 ± 0.76 μM (mean ± SD, n = 10), while the concentration in the CSF of a group of control patients was 0.38 ± 0.14 μM ( n = 10; p < .01). The mean concentration of HNE in the plasma of Parkinson’s patients was 0.68 ± 0.15 μM ( n = 20) and the concentration in the control group was 0.47 ± 0 12 μM ( n = 20; p < .05). The mean peak concentration of HNE in the brainstem of mice after a single s.c. dose of MPTP (40 mg/kg) was 3.62 ± 0.36 nM/g wet wt. ( n = 17) at 12 h while the control value was 0.45 ± 0.05 nM/g wet wt. ( n = 20; p < .05). The GSH concentration in the brainstem of MPTP-treated mice at 24 h. was 0.65 ± 0.03 μM/g wet wt. ( n = 14) and the control value was 1.25 ± 0.03 μM/g wet wt. ( n = 20; p < .01). The corresponding concentration of GSH-HNE-conjugate at 24 h was 0.32 ± 0.09 μM/g wet wt. ( n = 12) compared with a control value of 0.05 ± 0.02 ( n = 16; p < .01). After treatment with α-tocopherol (2.35 g/kg s.c. daily × 3) the mean concentration of HNE 12 hr. after MPTP injection was 0.89 ± 0.06 nM/g wet wt. ( n = 18). The HNE concentration in a group not treated with α-tocopherol prior to MPTP injection was 3.49 ± 0.09 nM/g wet wt. ( n = 14; p < .05). The concentration of GSH in the mice pretreated with α-tocopherol before MPTP injection was 1.14 ± 0.02 μM/g wet wt. ( n = 17) at 24 h compared to 0.61 ± 0.02 μM/g wet wt. ( n = 14) in the untreated mice ( p < .05). The direct injection of HNE (1, 10, 100, 1,000 μM) into the substantia nigra caused a dose dependent depletion of GSH in the brainstem of mice. The mean concentration of GSH 24 hr after the injection of 100 μM of HNE was 0.43 ± 0.22 μM/g wet wt. ( n = 4) compared with a control value of 1.48 ± 0.02 μM/g wet wt. ( n = 8; p < .05). The corresponding concentration of GSH-HNE-conjugate was 0.32 ± 0.12 μM/g wet wt. ( n = 4) while the control value was 0.04 ± 0.02 μM/g wet wt. ( n = 8). These data suggest that HNE may be a causeative neurotoxin in Parkinson’s disease and that HNE may also be involved in MPTP toxicity.

Immunoregulatory and anti-inflammatory effects of n-3 polyunsaturated fatty acids.

1. Fish oils are rich in the long-chain n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids. Linseed oil and green plant tissues are rich in the precursor fatty acid, alpha-linolenic acid (18:3n-3). Most vegetable oils are rich in the n-6 PUFA linoleic acid (18:2n-6), the precursor of arachidonic acid (20:4n-6). 2. Arachidonic acid-derived eicosanoids such as prostaglandin E2 are pro-inflammatory and regulate the functions of cells of the immune system. Consumption of fish oils leads to replacement of arachidonic acid in cell membranes by eicosapentaenoic acid. This changes the amount and alters the balance of eicosanoids produced. 3. Consumption of fish oils diminishes lymphocyte proliferation, T-cell-mediated cytotoxicity, natural killer cell activity, macrophage-mediated cytotoxicity, monocyte and neutrophil chemotaxis, major histocompatibility class II expression and antigen presentation, production of pro-inflammatory cytokines (interleukins 1 and 6, tumour necrosis factor) and adhesion molecule expression. 4. Feeding laboratory animals fish oil reduces acute and chronic inflammatory responses, improves survival to endotoxin and in models of autoimmunity and prolongs the survival of grafted organs. 5. Feeding fish oil reduces cell-mediated immune responses. 6. Fish oil supplementation may be clinically useful in acute and chronic inflammatory conditions and following transplantation. 7. n-3 PUFAs may exert their effects by modulating signal transduction and/or gene expression within inflammatory and immune cells.

Substrates for hypothalamic PGE2 synthesis are not decreased in cholestatic rats.

We have recently described impaired IL-1 beta-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis in cholestatic rats and have implicated defective IL-1 beta-mediated hypothalamic generation of PGE2 in this finding. Since patients with obstructive cholestasis have decreased levels of PGE2 precursor fatty acids in their red blood cell membranes (arachidonic acid) we speculated that a similar deficiency of membrane prostaglandin percursor fatty acids in the hypothalamus of cholestatic rats may contribute to the defective cytokine-mediated PGE2 generation we have previously described. Therefore, in this study we determined red blood cell and hypothalamic membrane fatty acid composition in rats with obstructive cholestasis due to bile duct resection and in non-cholestatic sham resected controls 5 days after operation. To do this red blood cell membrane and hypothalamic membrane fatty acids were extracted, methyl esterified and quantified by gas liquid chromatography. Similar to results found in patients with obstructive cholestasis, bile duct resected rats had significantly reduced levels of red blood cell membrane arachidonic acid compared to levels in sham resected controls (p < or = 0.02). However, bile duct resected and sham resected rats had similar levels of hypothalamic membrane arachidonic acid. Therefore, these results suggest that the impaired IL-1 beta-induced HPA axis activation in cholestatic rats cannot be explained by lower hypothalamic membrane levels of the PGE2 substrate arachidonic acid in these animals. Furthermore, our results suggest that the brain in cholestasis appears to be protected from membrane fatty acid composition alterations which are seen outside the blood-brain-barrier.

Dietary Juniperis virginiensis seed oil decreased pentobarbital-associated mortalities among DBA/1 mice treated with collagen-adjuvant emulsions

The propensity of the fatty acid 5,11,14 eicosatrienoic acid (5,11,14-ETA) to replace arachidonic acid in cell membranes, and its inability to be converted to bioactive eicosanoids, suggest that it may be useful in the treatment of autoimmune disorders. Previously, dietary application of oils extracted from 5,11,14-ETA-rich Platycladus orientalis delayed the onset of autoimmune disease in New Zealand Black mice. To gain more knowledge of the efficacy of this fatty acid toward alleviating immunological disorders, a similar oil was used to examine its effects on collagen-induced arthritis in DBA/1 mice, a model characterized by synovial proliferation and joint infiltration by inflammatory cells. Mice were fed AIN76A diet supplemented with 4% ( w w ) of either an oil extracted from the seeds of Juniperis virginiensis (0.4% 5,11,14-ETA); a control oil consisting of equal parts olive, linseed and safflower oils; fish oil (90% fish oil and 10% safflower oil); or safflower oil. Mice were immunized with three injections of collagen-adjuvant emulsions, the first injection was intradermal, and the two subsequent injections were intraperitoneal. Mortalities were recorded following a secondary pentobarbital administration intraperitoneally. Mice from the J. virginiensis group had the lowest mortalities (25%) while safflower oil-fed mice had the highest (59%v; p < 0.05). While the J. virginiensis group had the lowest mean CD4 CD8 T lymphocyte ratio, the fish oil group had the highest. These observations suggest that manipulation of eicosanoid production by different dietary lipids had different effects on immune responses, possibly through alterations in T lymphocyte subsets. Hypothetically, a downregulation of prostaglandin E2 release could increase the ratio of T helper 1 to T helper 2 lymphocytes and thereby modulate anaphylactic responses. Also, lowered pro-oxidant status may decrease CD4 CD8 T cell ratios and modify immune function.

PGA1 and PGA2 are selective ligands for the EP2 and EP4 prostaglandin receptor subtypes

The arachidonic acid (AA) metabolism pathways play a key role in immunological response and inflammation diseases, such as asthma, etc. AA in cell membranes can be metabolized by lipoxygenases (LOXs) to a screen of bioactive substances that include leukotrienes (LTs), lipoxins (LXs), and eicosatetraenoic acids (ETEs), which are considered closely related to the pathophysiology of respiratory allergic disease. Studies also verified that drugs regulating AA LOXs pathway have better rehabilitative intervention for asthma. This review aims to summarize the physiological and pathophysiological importance of AA LOXs metabolism pathways in asthma and to discuss its prospects of therapeutic strategies.