Search results for "cyclooxygenase"
showing 10 items of 235 documents
Heme oxygenase-1 induction by nitric oxide in RAW 264.7 macrophages is upregulated by a cyclo-oxygenase-2 inhibitor.
2001
Unstimulated RAW 264.7 macrophages express negligible heme oxygenase-1 (HO-1) protein but incubation with the nitric oxide (NO) donor spermine nonoate (SPNO) induced HO-1 and weakly cyclo-oxygenase-2 (COX-2) protein. This effect was potentiated by coincubation with the COX-2 selective inhibitor, SC58125. Cells incubated with SPNO showed a strong increase in HO-1 mRNA levels after 4 h with a significant potentiation in the presence of SC58125, which did not modify HO-1 mRNA stability. The induction of HO-1 by NO and its potentiation by anti-inflammatory agents may play a role in inflammatory and immune responses.
Role of NO-synthases and cyclooxygenases in the hyperreactivity of male rabbit carotid artery to testosterone under experimental diabetes.
2009
Abstract Cardiovascular disease is the major cause of morbidity and mortality in diabetic patients, which in turn is also associated with low levels of serum testosterone. The working hypothesis was that diabetes might modify the mechanisms involved in the vascular actions of testosterone in isolated rabbit carotid arteries. Testosterone (10 −8 –3 × 10 −4 M) induced a concentration-dependent relaxation of precontracted carotid arteries, which was higher in diabetic than in control rabbits. In control rabbits neither endothelium removal nor the nitric oxide synthase (NOS) inhibitor N G -nitro- l -arginine ( l -NOArg, 10 −5 M) modified the relaxant action of testosterone, and the cyclooxyge…
Mechanisms involved in the relaxant action of testosterone in the renal artery from male normoglycemic and diabetic rabbits.
2009
Kidney disease is a frequent complication in diabetes, and significant differences have been reported between male and female patients. Our working hypothesis was that diabetes might modify the vascular actions of testosterone in isolated rabbit renal arteries and the mechanisms involved in these actions. Testosterone (10(-8) to 10(-4)M) induced relaxation of precontracted arteries, without significant differences between control and diabetic rabbits. Both in control and diabetic rabbits endothelium removal inhibited testosterone relaxant action. In arteries with endothelium, incubation with indomethacin (10(-5)M), N(G)-nitro-l-arginine (10(-5)M) or tetraethylammonium (10(-5)M) did not modi…
Facilitation of Insulin Effects by Ranolazine in Astrocytes in Primary Culture
2022
Ranolazine (Rn) is a drug used to treat persistent chronic coronary ischemia. It has also been shown to have therapeutic benefits on the central nervous system and an anti-diabetic effect by lowering blood glucose levels and however, no effects of Rn on cellular sensitivity to insulin (Ins) have been demonstrated yet. The present study aimed to investigate the permissive effects of Rn on the actions of Ins in astrocytes in primary culture. Ins at 10-8 M, Rn (10-6 M) and Ins+Rn (10-8 M and 10−6 M respectively) were added to astrocytes during 24 h. In comparison to control cells, Rn and/or Ins caused modifications in cell viability and proliferation. p-AKT, p-ERK, p-eNOS, Mn-SOD, COX-2, and t…
Oleanonic acid, a 3-oxotriterpene from Pistacia, inhibits leukotriene synthesis and has anti-inflammatory activity.
2001
One of the best known bioactive triterpenoids is oleanolic acid, a widespread 3-hydroxy-17-carboxy oleanane-type compound. In order to determine whether further oxidation of carbon 3 affects anti-inflammatory activity in mice, different tests were carried out on oleanolic acid and its 3-oxo-analogue oleanonic acid, which was obtained from Pistacia terebinthus galls. The last one showed activity on the ear oedema induced by 12-deoxyphorbol-13-phenylacetate (DPP), the dermatitis induced by multiple applications of 12-O-tetradecanoyl-13-acetate (TPA) and the paw oedemas induced by bradykinin and phospholipase A2. The production of leukotriene B4 from rat peritoneal leukocytes was reduced by ol…
Synthesis and Evaluation of a Novel Series of Pyrrolizine Derivatives as Dual Cyclooxygenase-1 and 5-Lipoxygenase Inhibitors
1997
The aim of our study was to investigate structure activity relationship following the replacement of the 6-phenyl substituent at the 6,7-diaryl-2,3-dihydropyrrolizine template by various heteroaromatic residues. In this context we developed a new, efficient, and highly sensitive test method for the screening of dual cyclooxygenase-1 (COX-1) and 5-lipoxygenase (5-LOX) inhibitors. We used human platelets as a source of COX-1 and human PMNLs as a source of 5-LOX. Both cell types were isolated from the same volume of blood. PGE2 and LTB4 respectively were determined by highly selective and sensitive ELISA kits, using monoclonal antibodies. For a single determination at most 0.5 mL whole blood i…
Non-steroidal Anti-inflammatory Agents, Part 19:E-2-Pyrrolizin-5-yl Acrylic Acids as Potent Dual or Selective Inhibitors of Bovine Cyclooxygenase and…
1995
The pyrrolizinyl substituted acrylic acid derivatives represent another class of dual and selective inhibitors of cyclooxygenase and 5-lipoxygenase. By modifying their substitution pattern at the phenyl moiety of C-6 the balance between the activity against cyclooxygenase and against 5-lipoxygenase can be shifted. Structure-activity relationships are discussed. Compound 6k is the most potent and well-balanced dual inhibitor of both enzymes, while the highest selectivity of lipoxygenase inhibition was found for 6j. The activity and selectivity of compounds with an additional sulfur moiety depend on the oxidation status of this atom, giving an indication of the discussed coupling between pero…
Influence of traditional Chinese anti-inflammatory medicinal plants on leukocyte and platelet functions.
2003
Abstract The enzymes 5-lipoxygenase and elastase are therapeutic targets in dermatological disorders such as psoriasis. Fifteen extracts from traditional Chinese medicinal plants used to treat topical inflammations were screened for their inhibitory effect on lipoxygenase, cyclooxygenase and elastase activity in intact leukocytes and platelets. Astragalus membranaceus, Forsythia suspensa and Poria cocos inhibited 5-lipoxygenase, with IC50 values of 141, 80 and 141 μg mL−1, respectively. The latter two species, along with Angelica dahurica and Angelica pubescens, also inhibited elastase (IC50 values of 80, 123, 68 and 93 μg mL−1, respectively), while A. pubescens, Atractylodes macrocephala, …
Cyclooxygenase-1/2 (COX-1/COX-2) and 5-lipoxygenase (5-LOX) inhibitors of the 6,7-diaryl-2,3-1H-dihydropyrrolizine type
2003
A series of 6,7-diaryl-2,3-1H-dihydropyrrolizines was prepared as COX-1/COX-2 and 5-LOX inhibitors. The inhibition of COX-1 was evaluated using intact bovine platelets as the enzyme source, whereas LPS-stimulated human monocytes served as the enzyme source for inducible COX-2. The determination of arachidonic metabolites was performed by HPLC for COX-1 and RIA for COX-2. The balance between COX-1/COX-2 and 5-LOX inhibition can be shifted by modifying the substitution pattern of the phenyl moiety at the 6- and 7-position of the pyrrolizine nucleus. Structure-activity relationships are discussed.
COX-1/COX-2 inhibitors based on the methanone moiety
2002
This paper focuses on the synthesis and the in vitro testing of dual COX-1/COX-2 inhibitors. Starting from structures of non-steroidal anti-inflammatory drugs (NSAIDs) the diaryl methanone element was chosen as a lead. Modifications were carried out on this scaffold to obtain potent inhibitors of the COX enzymes. The N-(2-aroylphenyl)sulphonamides and -amides were studied in detail, and to consolidate the data evaluated the corresponding 3- and 4-regioisomers were also investigated. The potency and the enzyme selectivity were varied by structural modifications of the lead.