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Lipoxygenase Inhibitor (lipoxygenase + inhibitor)
Selected AbstractsChemInform Abstract: Synthesis of New 1-(2-, 3-, or 4-Methanesulfonylphenyl)-2-[5-(N-hydroxypyridin-2(1H)-one)]acetylene Regioisomers: A Search for Novel Cyclooxygenase and Lipoxygenase Inhibitors.CHEMINFORM, Issue 31 2009Morshed A. Chowdhury Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Effects of Endotoxin Exposure on Cationic Amino Acid Transporter Function in Ovine Peripheral Blood Mononuclear CellsEXPERIMENTAL PHYSIOLOGY, Issue 2 2003Megan F. Clark Rodent models of sepsis differ from clinical human disease in that humans make substantially less whole-body nitric oxide and have different cellular responses to endotoxin. Sheep, when exposed to endotoxin, behave in a manner more similar to humans. Many studies of rodent peripheral blood mononuclear cells (PBMCs) exposed to endotoxin demonstrate increased cationic amino acid transporter function (particularly through the y+ transporter) to supply arginine substrate to upregulated nitric oxide synthase. Whether this is true in sheep is not known. We have studied cationic amino acid transport in sheep PBMCs stimulated with endotoxin, using labelled lysine. PBMCs stimulated both in vitro and in vivo show an initial reduction in total and y+ lysine transport (after 1-2 h exposure to endotoxin): a previously undescribed effect of endotoxin. In in vitro activated cells, the reduction in y+ transport was prevented by the lipoxygenase inhibitor, nordihydroguaretic acid (NDGA), and the phospholipase inhibitor 4-bromophenacyl bromide (4-BPAB), but not cyclohexamide or a number of other inhibitors of intracellular second-messenger pathways. In contrast after 14 h incubation, the expected increase in total and y+ lysine transport was seen. The increase in y+ transport could be prevented by cyclohexamide, dexamethasone, ibuprofen, the protein kinase C inhibitor sphingosine, NDGA and 4-BPAB. These results suggest that in response to endotoxin exposure there is an initial decrease in y+ activity mediated by a lipoxygenase product, followed by a substantial increase in y+ activity mediated by the products of either cyclo-oxygenase or lipoxygenase. Cyclo-oxygenase and/or lipoxygenase inhibition might be useful in reducing arginine transport, and hence nitric oxide production, in these cells. [source] Effectiveness of Boswellia serrata extract supplemented with a synthetic lipoxygenase inhibitor in the treatment of knee osteoarthritisFOCUS ON ALTERNATIVE AND COMPLEMENTARY THERAPIES AN EVIDENCE-BASED APPROACH, Issue 4 2008Article first published online: 3 JUN 2010 [source] Nordihydroguaiaretic acid induces astroglial death via glutathione depletionJOURNAL OF NEUROSCIENCE RESEARCH, Issue 14 2007Joo-Young Im Abstract Nordihydroguaiaretic acid (NDGA) is known to cause cell death in certain cell types that is independent of its activity as a lipoxygenase inhibitor; however, the underlying mechanisms are not fully understood. In the present study, we examined the cellular responses of cultured primary astroglia to NDGA treatment. Continuous treatment of primary astroglia with 30 ,M NDGA caused >85% cell death within 24 hr. Cotreatment with the lipoxygenase products 5-HETE, 12-HETE, and 15-HETE did not override the cytotoxic effects of NDGA. In assays employing the mitochondrial membrane potential-sensitive dye JC-1, NDGA was found to induce a rapid and almost complete loss of mitochondrial membrane potential. However, the mitochondrial permeability transition pore inhibitors cyclosporin A and bongkrekic acid did not block NDGA-induced astroglial death. We found that treatment with N-acetyl cysteine (NAC), glutathione (GSH), and GSH ethyl ester (GSH-EE) did inhibit NDGA-induced astroglial death. Consistently, NDGA-induced astroglial death proceeded in parallel with intracellular GSH depletion. Pretreatment with GSH-EE and NAC did not block NDGA-induced mitochondrial membrane potential loss, and there was no evidence that reactive oxygen species (ROS) production was involved in NDGA-induced astroglial death. Together, these results suggest that NDGA-induced astroglial death occurs via a mechanism that involves GSH depletion independent of lipoxygenase activity inhibition and ROS stress. © 2007 Wiley-Liss, Inc. [source] Isolation of eriocitrin (eriodictyol 7- O -rutinoside) as an arachidonate lipoxygenase inhibitor from Lumie fruit (Citrus lumia) and its distribution in Citrus speciesJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 1 2007Yoichi Nogata Abstract An inhibitory compound acting against rat platelet 12-lipoxygenase was isolated from the peel of Lumie fruit (Citrus lumia) by activity-guided separation. It was identified as eriocitrin (eriodictyol 7- O -rutinoside) by spectroscopic analyses. Eriocitrin inhibited 5-lipoxygenase (IC5029.1 µmol L,1) from rat peritoneal polymorphonuclear leukocytes in addition to 12-lipoxygenase (IC5022.3 µmol L,1). Its aglycone, eriodictyol (5,7,3,, 4,-tetrahydroxyflavanone), was a much more potent inhibitor of both 12-lipoxygenase (IC500.07 µmol L,1) and 5-lipoxygenase (IC500.20 µmol L,1). It also inhibited the production of leukotriene B4 in intact peritoneal polymorphonuclear leukocytes stimulated with calcium ionophore A23187 (IC5012.7 µmol L,1). The distribution of eriocitrin in 39 citrus fruits was investigated by high-performance liquid chromatography analysis. Lumie, eureka lemon (Citrus limon), Sambokan (Citrus sulcata), Sudachi (Citrus sudachi) and Koji (Citrus leiocarpa) fruits were found to contain high levels of eriocitrin in both peel and juice vesicles. Copyright © 2006 Society of Chemical Industry [source] Targeted lipidomics using electron capture atmospheric pressure chemical ionization mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 19 2003Seon Hwa Lee There is an increasing need to be able to conduct quantitative lipidomics analyses as a complement to proteomics studies. The highest specificity for proteomics analysis can be obtained using methodology based on electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI) coupled with liquid chromatography/tandem mass spectrometry (LC/MS/MS). For lipidomics analysis it is often necessary to be able to separate enantiomers and regioisomers. This can be very challenging when using methodology based on conventional reversed-phase chromatography. Normal-phase chromatography using chiral columns can provide dramatic improvements in the resolution of enantiomers and regioisomers. However, conventional ESI- and APCI-MS/MS has limited sensitivity, which makes it difficult to conduct studies in cell culture systems where only trace amounts of non-esterified bioactive lipids are present. The use of electron capture APCI-MS/MS overcomes this problem. Enantiomers and regioisomers of diverse bioactive lipids can be quantified using stable isotope dilution methodology coupled with normal-phase chiral chromatography and electron capture APCI-MS/MS. This methodology has allowed a lipidomics profile from rat epithelial cells maintained in culture to be delineated and allowed the effect of a non-selective lipoxygenase inhibitor to be assessed. Copyright © 2003 John Wiley & Sons, Ltd. [source] Eicosanoids mediate the laminarin-induced nodulation response in larvae of the flesh fly, Neobellieria bullataARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 1 2005Vanessa Franssens Abstract Insects have a highly developed innate immune system, including humoral and cellular components. The cellular immune responses refer to hemocyte-mediated processes such as phagocytosis, nodulation, and encapsulation. Nodulation is considered the predominant defense reaction to infection in insects. Treating third instar larvae of the grey flesh fly, Neobellieria bullata, with laminarin (,-1,3-glucan, a typical component of fungal cell walls) induced nodulation in a dose-dependent manner. This reaction was initiated very soon after injection and reached its maximal response level after 4 h. The nodules were not randomly distributed in the hemocoel, but were concentrated around the crop. The possible role of eicosanoids in this nodulation process was determined by treating larvae with the phospholipase A2 inhibitor, dexamethasone, the cyclooxygenase inhibitor, naproxen, and the lipoxygenase inhibitor, esculetin. Both dexamethasone and naproxen significantly impaired the ability of N. bullata larvae to form nodules in response to laminarin. Supplying dexamethasone-treated larvae with the eicosanoid precursor, arachidonic acid, restored the full response. On the other hand, treating larvae with esculetin did not influence the formation of nodules in response to laminarin. This is the first study that demonstrates the occurrence of a laminarin-induced nodulation response in Diptera. Phospholipase A2 and cyclooxygenase activities, both involved in prostaglandin biosynthesis, appear to play an important role in the regulation of this process. Arch. Insect Biochem. Physiol. 59:32,41, 2005. © 2005 Wiley-Liss, Inc. [source] Interactions between CB1 receptors and TRPV1 channels mediated by 12-HPETE are cytotoxic to mesencephalic dopaminergic neuronsBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2008S R Kim Background and purposes: We recently proposed the existence of neurotoxic interactions between the cannabinoid type 1 (CB1) receptor and transient receptor potential vanilloid 1 (TRPV1) channels in rat mesencephalic cultures. This study seeks evidence for the mediator(s) and mechanisms underlying the neurotoxic interactions between CB1 receptors and TRPV1 in vitro and in vivo. Experimental approach: The mediator(s) and mechanism(s) for the interactions between CB1 receptors and TRPV1 were evaluated by cell viability assays, immunocytochemistry, Fura-2 calcium imaging, mitochondrial morphology assay, ELISA and Western blot assay in vitro in neuron-enriched mesencephalic cultures. Injections into the substantia nigra and subsequent cell counts were also used to confirm these interactions in vivo. Key results: The neurotoxic interactions were mediated by 12(S)-hydroperoxyeicosatetraenoic acid (12(S)-HPETE), an endogenous TRPV1 agonist. CB1 receptor agonists (HU210 and WIN55,212-2) increased the level of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), a downstream metabolite of 12(S)-HPETE, which stimulates TRPV1-mediated death of mesencephalic neurons, both in vitro and in vivo. The neurotoxicity was mediated by increased intracellular Ca2+ concentration ([Ca2+]i) through TRPV1, consequently leading to mitochondrial damage and was attenuated by baicalein, a 12-lipoxygenase inhibitor. Conclusion and implications: Activation of CB1 receptors in rat mesencephalic neurons was associated with biosynthesis of 12(S)-HPETE, which in turn stimulated TRPV1 activity, leading to increased [Ca2+]i, mitochondrial damage and neuronal death. British Journal of Pharmacology (2008) 155, 253,264; doi:10.1038/bjp.2008.246; published online 16 June 2008 [source] New and emerging treatments in dermatology: acneDERMATOLOGIC THERAPY, Issue 2 2008A. Katsambas ABSTRACT:, Topical retinoids, benzoyl peroxide, azelaic acid, and topical and oral antibiotics remain the milestone of treatment for mild to moderate acne vulgaris. Oral isotretinoin is useful for the treatment of severe nodular acne, treatment-resistant acne, and acne with a risk of physical or psychological scarring. Hormonal treatment in female acne is useful in resistant or late-onset acne. With increasing concerns regarding teratogenicity of isotretinoin and increasing antibiotic resistance, there is a clear need for therapeutic alternatives to these long-used treatments. Research in the pathogenesis of acne has allowed for new therapies and future perspectives regarding acne to evolve. They include low-dose long-term isotretinoin regimens, insulin-sensitizing agents, 5,-reductase type 1 inhibitors, topical photodynamic therapy, new combination formulations, dietary interventions, and antiinflammatory agents such as lipoxygenase inhibitors. [source] Inhibition of Oxidative and Antioxidative Enzymes by Trans-ResveratrolJOURNAL OF FOOD SCIENCE, Issue 2 2001X. Fan ABSTRACT: Trans-resveratrol, a phytoalexin produced by a variety of plants, has been shown to inhibit oxidative enzymes in an animal cell system. Its effect on several oxidative and antioxidative enzymes from plants was investigated using in vitro assays. Trans-resveratrol inhibited superoxide dismutase, lipoxygenase, catalase, peroxidase, polyphenol oxidase, and 1-aminocyclopropane-1-carboxylic acid oxidase with apparent KI's of 10, 90, 100, 255, 305, and 350 ,M, respectively. Trans-resveratrol inhibited lipoxygenase activity more effectively than other lipoxygenase inhibitors, including propyl gallate, ibuprofen, ursolic acid, acetylsalicylic acid, and salicylhydroxamic acid. [source] Spinal administration of lipoxygenase inhibitors suppresses behavioural and neurochemical manifestations of naloxone-precipitated opioid withdrawalBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2003Tuan Trang This study investigated the role of spinal lipoxygenase (LOX) products in the induction and expression of opioid physical dependence using behavioural assessment of withdrawal and immunostaining for CGRP and Fos protein expression in the spinal cord. Administration of escalating doses (5,50 mg kg,1; i.p.) of morphine for 5 days markedly elevated CGRP-like immunoreactivity in the dorsal horn of the rat spinal cord. Naloxone (2 mg kg,1; i.p.) challenge precipitated a robust withdrawal syndrome that depleted CGRP-like immunoreactivity and increased the number of Fos-like immunoreactive neurons in the dorsal horn. Intrathecal administration of NDGA (10, 20 ,g), a nonselective LOX inhibitor, AA-861 (1.5, 3 ,g), a 5-LOX selective inhibitor, or baicalein (1.4, 2.8 ,g), a 12-LOX selective inhibitor, concurrently with systemic morphine for 5 days or as a single injection immediately preceding naloxone challenge, blocked the depletion of CGRP-like immunoreactivity, prevented increase in the number of Fos-like immunoreactive neurons in the dorsal horn, and significantly attenuated the morphine withdrawal syndrome. The results of this study suggest that activity of LOX products, at the spinal level, contributes to the expression of opioid physical dependence, and that this activity may be expressed through increased sensory neuropeptide release. British Journal of Pharmacology (2003) 140, 295,304. doi:10.1038/sj.bjp.0705440 [source] Photoactivation of an Inhibitor of the 12/15-Lipoxygenase PathwayCHEMBIOCHEM, Issue 7 2006Stephan Herre Abstract Lipoxygenases are lipid-peroxidizing enzymes that have been implicated in the pathogenesis of inflammatory diseases and lipoxygenase inhibitors may be developed as anti-inflammatory drugs. Structure comparison with known lipoxygenase inhibitors has suggested that (2Z)-2-(3-benzylidene)-3-oxo-2,3-dihydrobenzo[b]thiophene-7-carboxylic acid methyl ester might inhibit the lipoxygenase pathway but we found that it exhibited only a low inhibitory potency for the pure 12/15-lipoxygenase (IC50=0.7 mM). However, photoactivation, which induces a Z -to- E isomerization of the double bond, strongly augmented the inhibitory potency and an IC50 value of 0.021 mM was determined for the pure E isomer. Similar isomer-specific differences were observed with the recombinant enzyme and its 12-lipoxygenating Ile418Ala mutant, as well as in intracellular lipoxygenase activity. Structure modeling of the enzyme/inhibitor complex suggested the molecular reasons for this isomer specificity. Since light-induced isomerization may proceed in the skin, such photoreactive compounds might be developed as potential drugs for inflammatory skin diseases. [source] | ||||||||||||||||