Search results for "Cyclooxygenase Inhibitors"
showing 10 items of 76 documents
Raloxifene increases the capacity of serum to promote prostacyclin release in human endothelial cells: implication of COX-1 and COX-2.
2004
OBJECTIVE Prostacyclin is a potent vasodilator synthesized by two isoforms of cyclooxygenase in endothelium. The aim of this study was to investigate the effect of serum from postmenopausal women treated with raloxifene on prostacyclin production by human umbilical vein endothelial cells and on cyclooxygenases-1 and -2. DESIGN Serum was collected from 21 women receiving 60 mg/day of raloxifene, at baseline and at 3 and 6 months. Human umbilical vein endothelial cells were exposed to serum for 24 hours, and prostacyclin production was evaluated in supernatants. Selective inhibitors of cyclooxygenases-1 and -2 (SC-560 and NS-398) were used to investigate the relative contribution of each enzy…
Efficient synthesis and 5-LOX/COX-inhibitory activity of some 3-hydroxybenzo[b]thiophene-2-carboxylic acid derivatives
2012
Abstract A series of 3-hydroxybenzo[ b ]thiophene-2-carboxylic acid derivatives has been prepared and subsequently evaluated with regards to the inhibition of 5-LOX/COX. Structure optimization furnished derivatives with promising in vitro activity as dual 5-LOX/COX inhibitors with submicromolar IC 50 values for inhibition of 5-LOX and COX-1, respectively.
Co-regulation between cyclo-oxygenase-2 and inducible nitric oxide synthase expression in the time-course of murine inflammation.
2000
Many in vitro studies have used cell cultures to focus on the relationships between cyclo-oxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) isoforms. We have investigated the time-course of regulation and the role of COX-2 and iNOS in a model of experimental inflammation in mice, the air pouch injected with zymosan. This study demonstrates that there is an early acute phase (4 h) mediated mainly by eicosanoids, with high levels of prostaglandin E2 (PGE2) produced by cyclo-oxygenase-1. In addition, in the later phase (from 12 h) there is a participation of nitric oxide (NO) and PGE2 accompanied by co-induction of both iNOS and COX-2. These enzymes were detected in migrating leuk…
Effects of cyclooxygenase-1/cyclooxygenase-2 inhibition on leukocyte/endothelial cell interactions in the rat mesentery.
2002
Nonsteroidal anti-inflammatory drugs (NSAID) inhibit cyclooxygenase activity and cause gastrointestinal damage in part by promoting leukocyte accumulation in the mucosa. Our aim was to evaluate the effects of selective blockade of the isoenzymes cyclooxygenase-1 and cyclooxygenase-2 on leukocyte adhesion in vivo. Leukocyte/endothelial cell interactions were examined in rat mesenteric venules before and after treatment with indomethacin, SC-560 (5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole, cyclooxygenase-1 inhibitor), DFP (5,5-dimethyl-3-(2-propoxy)-4-(4-methanesulfonyl)-2(5H)-furanone, cyclooxygenase-2 inhibitor), or SC-560 plus DFP (20 mg/kg, i.v. each). Indomethacin i…
Anti-inflammatory profile of dehydrocostic acid, a novel sesquiterpene acid with a pharmacophoric conjugated diene
2005
Sesquiterpene acids are natural products that, in contrast with the thoroughly studied sesquiterpene lactones, have received little pharmacological attention. A good source of this class of compounds is Inula viscosa (Asteraceae), a plant with documented anti-inflammatory effects. The present paper gives the results of our investigations on the biochemical mechanisms involved in the anti-inflammatory activity of one such compound, dehydrocostic acid. The most salient findings were that in vitro dehydrocostic acid inhibits leukotriene B(4) production (IC(50)=22 microM), elastase activity (IC(50)=43 microM) and bee venom phospholipase A(2) activity (IC(50)=17 microM). Furthermore, this sesqui…
Effect of aspirin on renal disease progression in patients with type 2 diabetes: A multicenter, double-blind, placebo-controlled, randomized trial. T…
2017
Background Type 2 diabetes mellitus (T2DM) is one of the most common causes of chronic kidney disease and kidney failure. It has been estimated that the annual decline of estimated glomerular filtration rate (eGFR) among patients with T2DM is approximately 2.0-2.5 mL min−1 y−1. Cyclooxygenase-dependent eicosanoids, such as 11-dehydro-thromboxane (Tx)B2, are increased in T2DM patients and are potentially involved in the regulation of renal blood flow. Animal models showed that cyclooxygenase inhibitors, such as aspirin, are associated with improvements in renal plasma flow and eGFR values. Hypothesis The primary end point of the LEDA trial is to evaluate the 1-year decline of eGFR in T2DM pa…
Indomethacin enhances endothelial NO release — evidence for a role of PGI2 in the autocrine control of calcium-dependent autacoid production
1998
Objective: We studied whether NO or prostacyclin (PGI2), which are continuously released by endothelial cells, have autocrine/paracrine effects on the calcium-dependent autacoid production by modulating the intracellular Ca2+ concentration ([Ca2+]i). Methods: Histamine(His)-induced [Ca2+]i increases (Fura 2-method) and NO-dependent cGMP increase were measured in human umbilical vein endothelial cells (HUVECs) before and after cyclooxygenase inhibition or application of cAMP- and cGMP-elevating drugs. Results: 0.3 μM His increased endothelial [Ca2+]i from 77±2 nM to 418±59 nM. The His-induced [Ca2+]i increases were significantly attenuated following treatment with PGI2 (by 23%) and forskolin…
Cyclo-oxygenase isoenzymes. How recent findings affect thinking about nonsteroidal anti-inflammatory drugs
1997
International audience; The discovery of at least 2 cyclo-oxygenase (COX) isoenzymes, referred to as COX-1 and COX-2, has updated our knowledge of nonsteroidal anti-inflammatory drugs (NSAIDs). This has lead investigators to reconsider what can be awaited from this class of drugs. The 2 COX isoenzymes share structural and enzymatic similarities, but are specifically regulated at the molecular level and may be distinguished apart in their functions, although some physiological overlap between them does occur. The major goal in developing selective COX inhibitors is to improve NSAID tolerability. Classic NSAIDs preferentially inhibit COX-1 in vitro, but it appears hazardous to judge their gas…
Nonsteroidal Antiinflammatory Agents, XVIII: C-5 Functionalized 6,7-Diphenyl-2,3-dihydro-1H-pyrrolizines as Inhibitors of Bovine Cyclooxygenase and 5…
1994
6-(4-Chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizines with functional groups at position 5 of the heterocyclic moiety were synthesized and tested. To determine their antiinflammatory activity bovine blood was used as enzyme source for the cyclooxygenase and 5-lipoxygenase, respectively. The iminoxy acetic acid derivative and the iminotetrazole selectively inhibit the 5-lipoxygenase, all the other compounds show medium or low affinity to the active sites of cyclooxygenase and 5-lipoxygenase. In general all compounds inhibit 5-lipoxygenase more effectively than cyclooxygenase. Concerning the inhibition of 5-lipoxygenase the most active compounds found are equipotent to the corresponding pro…
Investigations Concerning the Correlation of COX-1 Inhibitory and Hydroxyl Radical Scavenging Activity
2008
The aim was to study the COX-1 inhibiting efficacy in context with hydroxyl radical scavenging properties of compounds bearing a carboxylic acid and ester function, respectively. In general, the acids are more potent radical scavengers than the corresponding esters but there is no clear correlation with their COX-1 inhibiting potencies. A feasible scavenging mechanism of carboxylic acids is discussed.