Cyclo-oxygenase

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Effects of selected cyclo-oxygenase inhibitors on cardiovascular preparations in rabbits

Effects of selected cyclo-oxygenase inhibitors on cardiovascular preparations in rabbits

Cyclo-oxygenase- (COX-) inhibitors are those drugs which have the ability to inhibit the activity of COX enzymes (types 1 and 2) resulting in inhibition of prostaglandin synthesis [1]. Two types of COX- inhibitors are established, the traditional non-selective non-steroidal anti-inflammatory drugs (NSAIDs) which block both types of COX. The second type is the selective COX-2 inhibitors which have no or minimal affinity, and thus, no effect on COX-1. The development of the COX-2 selective inhibitors was intended to provide drugs that would offer the same pain-relieving and anti-inflammatory effects as the traditional NSAIDs without causing the gastric ulcers and nephrotic effects that have been associated with the pioneer drugs [2].
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Immunoexpression of constitutive and inducible cyclo-oxygenase isoforms in the rat foetal and maternal digestive tract

Immunoexpression of constitutive and inducible cyclo-oxygenase isoforms in the rat foetal and maternal digestive tract

Numerous experimental and clinical studies have shown that cyclo-oxygenase inhibitors, also known as non-steroidal anti-inflammatory drugs, may dam- age the gastrointestinal mucosa. The harmful effect is mediated by various mechanisms including topical injury, increased expression of intercellular adhesion molecules, thromboxane depletion, and probably the most important, inhibition of prostaglandin synthe- sis [12, 22]. 6-keto-prostaglandins increase epithelial cell proliferation, stimulates mucin, bicarbonate and phospholipid secretion, which protects the gas- troduodenal mucosa against hydrochloric acid, pep- sin and bile salts. Unlike that of gastroduodenal inju- ry, the pathogenesis of oesophageal, jejunal and ileal mucosa injury is still unclear. It is suggested that the drugs, in spite of prostaglandin synthesis blockade, directly uncouple oxidative metabolism in the mito- chondria of the enterocytes. This leads to cell dam- age and an increase in intestinal mucosal permeabil- ity, thus permits bacteria and bile from the lumen to penetrate the intestinal wall and to cause deep dam- age [19, 22].
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First dose analgesic effect of the cyclo oxygenase 2 selective inhibitor lumiracoxib in osteoarthritis of the knee: a randomized, double blind, placebo controlled comparison with celecoxib [NCT00267215]

First dose analgesic effect of the cyclo oxygenase 2 selective inhibitor lumiracoxib in osteoarthritis of the knee: a randomized, double blind, placebo controlled comparison with celecoxib [NCT00267215]

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely regarded as the agents of choice when treating the chronic pain of osteoarthritis (OA) [1-3]. This class of drugs prevents prostaglandin synthesis by nonselectively inhibiting both iso- forms of cyclo-oxygenase (COX) [4,5]; this profile also accounts for their common side effects, including gastric irri- tation, renal impairment and inhibition of platelet aggregation [6-9]. NSAID use is associated with an increased risk for gas- trointestinal ulcers and associated ulcer complications such as bleeds and perforations [7]. COX-2 selective inhibitors have demonstrated analgesic and anti-inflammatory efficacies comparable with those of traditional NSAIDs in patients with arthritis, combined with an improved safety profile [10-13]. Lumiracoxib (Prexige ® , Novartis Pharma AG, Basel, Switzer-
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Candida albicansinduces cyclo oxygenase 2 expression and prostaglandin E2 production in synovial fibroblasts through an extracellular regulated kinase 1/2 dependent pathway

Candida albicansinduces cyclo oxygenase 2 expression and prostaglandin E2 production in synovial fibroblasts through an extracellular regulated kinase 1/2 dependent pathway

Cyclo-oxygenase 2 (COX-2) expression following co-culture of Cand- ida albicans with synovial fibroblasts. COX-2 expression by synovial fibroblasts was assessed after 12-h co-culture of synovial fibroblasts with different seeding densities of C. albicans. (a) Gene expression. A representative agarose gel demonstrating COX-2 mRNA expression as assessed by reverse transcription polymerase chain reaction (RT-PCR). Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) served as internal control. The graph shows the results of densitometric analysis of DNA bands expressed as the mean ± standard deviation (SD) of the relative fold change in COX-2/GAPDH ratio with the ratio of the control condition normalized to 1 (N = 6, * P < 0.05). (b) Protein expression. A representative western blot of COX-2 protein expression following infection by C. albicans with tubulin as an internal protein loading con- trol. The graph shows the results of densitometric analysis of bands expressed as the mean ± SD of the relative change in COX-2/tubulin ratio with the ratio of the control condition normalized to 1 (N = 5, * P < 0.05).
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Epstein-Barr Virus Protein Can Upregulate Cyclo-Oxygenase-2 Expression through Association with the Suppressor of Metastasis Nm23-H1

Epstein-Barr Virus Protein Can Upregulate Cyclo-Oxygenase-2 Expression through Association with the Suppressor of Metastasis Nm23-H1

Previous studies have demonstrated the interaction between the Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA3C) and the metastatic suppressor Nm23-H1 both in vitro and in vivo (C. Subramanian, M. A. Cotter II, and E. S. Robertson, Nat. Med. 7:350–355, 2001). EBNA3C can reverse the ability of Nm23-H1 to suppress migration of Burkitt’s lymphoma and breast carcinoma cell lines in vitro. EBNA3C contributes to EBV- associated human cancers by regulating transcription of a number of cellular and viral promoters and by targeting and altering the transcription activities of the metastasis suppressor Nm23-H1. Cyclo-oxygenase-2 (COX-2), an inducible enzyme important in inflammation, is overexpressed in a variety of cancers and can influence cell migration. In this report we show that Nm23-H1 and EBNA3C can modulate expression of COX-2 in the context of EBV infection and transformation. The levels of COX-2 were consistently higher in EBV- positive cells than in EBV-negative cells. Additionally, we show that Nm23-H1 can upregulate the COX-2 promoter element in luciferase reporter assays, whereas EBNA3C alone did not affect the level of response but clearly contributed to an additive increase when coexpressed with Nm23-H1. The downstream effect of COX-2 expression was also evaluated and showed that prostaglandin E 2 levels increased with Nm23-H1 and that there
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The Association between Cyclo-oxygenase Inhibitor Medications and Clinical Relapse in Inflammatory Bowel Disease: Review of Current Perspectives

The Association between Cyclo-oxygenase Inhibitor Medications and Clinical Relapse in Inflammatory Bowel Disease: Review of Current Perspectives

Arachidonic acid is the precursor for the eicosanoids (that is mediators derived from 20- carbon polyunsaturated fatty acids); these include several families of mediators, predominantly prostaglandin (PG), thromboxane (TX) and leukotriene (LT) families. The polyunsaturated omega-6 fatty acid arachidonic acid is metabolised via three different pathways, the cyclo-oxygenase, the lipoxygenase and the cytochrome P450 pathways [11,20,21]. It is via the COX pathway that prostaglandins are formed, whereas it is currently believed that metabolism of arachidonic acid through the lipooxygenase and cytochrome P450 pathways generally produces non-prostaglandin family mediators: the leukotrienes, lipoxins hydroxyeicosatetraenoic (HETE), epoxyeicosatrienoic acid (EET) and hydroperoxyeicosatetraenic acid (5-HPETE). [11,20,21]. The isozymes COX-1 and COX-2 catalyse the production of PGH2 (prostaglandin H2) from arachidonic acid which is then metabolized by specific prostaglandin and thromboxane synthases to produce PGI2 (prostacyclin), PGD2, PGE2, PGF2 and TXA2 (thromboxane A2) [22]. COX-2 is the inducible form of the enzyme and its expression is up- regulated during inflammation. COX-1 is generally regarded as a constitutive (‘housekeeping’) non-inducible enzyme with widespread tissue distrubtion.
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Mechanisms underlying the growth inhibitory effects of the cyclo oxygenase 2 inhibitor celecoxib in human breast cancer cells

Mechanisms underlying the growth inhibitory effects of the cyclo oxygenase 2 inhibitor celecoxib in human breast cancer cells

Various mechanisms may be responsible for the observed effects of NSAIDs against breast cancer. Inhibition of cyclo- oxygenase (COX), particularly the COX-2 isozyme, and block- ade of the prostaglandin (PG) cascade may have impacts on neoplastic growth and development by inhibiting several key features of mammary carcinogenesis – namely proliferation, angiogenesis and metastasis. Inhibition of COX also causes induction of apoptosis in malignant cells and enhances antin- eoplastic activity of cytotoxic T lymphocytes [5-8]. Our study conducted in newly diagnosed stage I and stage II breast can- cer patients [9] showed impaired functionality of T cells and dendritic cells, which correlated with COX-2 overexpression in the tumors and increased levels of PGE 2 in the serum and tumor milieu. Therefore, a convincing case has been made for COX-2 being an important target for the antineoplastic action of NSAIDs. Unlike NSAIDs, COX-2 selective inhibitors such as celecoxib and rofecoxib do not inhibit COX-1 and thus show promise as drugs that spare the gastrointestinal system. COX-2 is overexpressed in breast cancer tissues, and greater extent of its expression is associated with poorer prognosis [10]. Various environmental and nutritional risk factors induce COX-2 expression in animal models of breast cancer [11,12]. Moreover, COX-2 selective inhibitors significantly delayed the incidence of mammary tumors in transgenic mice expressing the Her2/Neu, and polyoma-middle T oncogenes [13,14]. Recently, a transgenic mouse model was developed in which the human COX-2 gene was expressed in the mammary gland under the control of the murine mammary tumor virus promoter [15]. That study demonstrated that enhanced COX-2 expres- sion strongly predisposes to transformation of the mammary gland in multiparous animals. These data strongly suggest that local expression of COX-2 is sufficient for in situ tumor initia- tion and/or progression. Another transgenic overexpression study with COX-2 targeted to the epidermis also supports the concept that COX-2 is a critical regulator of tumor progression [16]. Transfections of the breast cancer cell line Hs578T with cDNA for COX-2 led to an increase in expression and activity of matrix metalloproteinase-2, resulting in increasingly invasive behavior of the cells [17]. COX-2 specific inhibitors have the ability to block cell growth, and induce apoptosis and cell cycle arrest in murine mammary tumor cell lines [18]. However, the molecular mechanisms involved are not well understood. If COX-2 inhibitors act only by modulating COX-2 expression, then that would imply that this therapy would be limited to COX-2 overexpressing tumors; hence, this question is of con- siderable clinical importance.
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EVALUATION OF AQUEOUS FRUIT EXTRACT OF TAMARINDUS INDICA (L) FOR INHIBITION OF TUMOR NECROSIS FACTOR a AND CYCLO OXYGENASE ENZYMES IN EXPERIMENTAL ANIMAL

EVALUATION OF AQUEOUS FRUIT EXTRACT OF TAMARINDUS INDICA (L) FOR INHIBITION OF TUMOR NECROSIS FACTOR a AND CYCLO OXYGENASE ENZYMES IN EXPERIMENTAL ANIMAL

Vol 11, Issue 3, 2018 Online 2455 3891 Print 0974 2441 EVALUATION OF AQUEOUS FRUIT EXTRACT OF TAMARINDUS INDICA (L) FOR INHIBITION OF TUMOR NECROSIS FACTOR a AND CYCLO OXYGENASE ENZYMES IN EXPERIMENTA[.]

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Role of Selective Cyclo Oxygenase 2 Inhibitor Celecoxib in Canine Osteosarcoma Cell Culture

Role of Selective Cyclo Oxygenase 2 Inhibitor Celecoxib in Canine Osteosarcoma Cell Culture

Background: Experimental studies have shown that cyclo-oxygenase-2 (Cox2) is related to the development and pro- gression of tumors, since this enzyme is induced and expressed by cells such as macrophages, osteoblasts, “activated” endothelial cells, and tumor cells. The activity in tumors includes proliferation, cell transformation, tumor growth, inva- sion and metastasis and may play an important role in carcinogenesis of the canine osteosarcoma, since it has high ex- pression in tissue fragments. The combination of selective Cox2 inhibitors and other treatment modalities is the basis for a new anti-cancer therapy strategy. This in vitro study exposed primary cells of five different canine osteosarcoma cultures to selective Cox2 inhibitor at increasing concentrations and times. Results: For Cox2 negative cultures, despite the absence of differences, greater sensitivity of cells to treatment was observed. For Cox2 positive cultures, a higher number of necrotic cells were observed (P ≤ 0.05), when compared with negative cultures. For exposure times with Celecoxib doses, no difference (P > 0.05) was found between the three times analyzed for living, apoptotic and apop- totic/necrotic cells. There are similarities in the values of 24 h and 48 h, with slight reduction of living cells, increasing those undergoing apoptosis and apoptosis/necrosis. There was significance for necrosis (P ≤ 0.05). In 72 hours, a sig- nificant difference was observed between the other two previous values (P ≤ 0.05). It was found for the group of 100 µM·L −1 , that there was a numerically greater signaling for apoptosis and lower (P = 0.08) for necrosis, and this point
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Cyclo oxygenase 2 selective inhibitors and nonsteroidal anti inflammatory drugs: balancing gastrointestinal and cardiovascular risk

Cyclo oxygenase 2 selective inhibitors and nonsteroidal anti inflammatory drugs: balancing gastrointestinal and cardiovascular risk

For complicated gastrointestinal events we chose to use data only from meta-analyses of randomised trials for celecoxib [28], etoricoxib [29], and valdecoxib [30], for rofecoxib we combi[r]

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Differential direct effects of cyclo oxygenase 1/2 inhibition on proteoglycan turnover of human osteoarthritic cartilage: an in vitrostudy

Differential direct effects of cyclo oxygenase 1/2 inhibition on proteoglycan turnover of human osteoarthritic cartilage: an in vitrostudy

cartilage Shown are the percentage changes compared with healthy cartilage of proteoglycan synthesis rate as a measure of cartilage matrix synthesis pg synthesis; percentage release of n[r]

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Dynamic compression counteracts IL 1β induced inducible nitric oxide synthase and cyclo oxygenase 2 expression in chondrocyte/agarose constructs

Dynamic compression counteracts IL 1β induced inducible nitric oxide synthase and cyclo oxygenase 2 expression in chondrocyte/agarose constructs

IL-1β induced iNOS and COX-2 and inhibited aggrecan expression Figure 2 illustrates the effects of IL-1β on the relative expression levels of iNOS, COX-2, aggrecan and collagen type II i[r]

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Hippocampal CA1 βCaMKII mediates neuroinflammatory responses via COX-2/PGE2 signaling pathways in depression

Hippocampal CA1 βCaMKII mediates neuroinflammatory responses via COX-2/PGE2 signaling pathways in depression

Results from previous studies have shown that the Ca 2+ -triggered activation of calcium/calmodulin-de- pendent protein kinases type II (CaMKIIs) are related to stress-induced depressive symptoms [3–6]. More- over, inhibition of CaMKII attenuates inflammatory- associated protein kinases and mediators in rat cerebrovascular inflammation [7]. Within spinal neu- rons, CaMKII acts as an upstream cascade to facilitate cyclo-oxygenase (COX)-2 transcription and expres- sion, which is involved in the development and/or maintenance of inflammatory pain [8]. COX-2 enzymatic hyperactivity can prompt production of the pro-inflammatory factor, PGE2. However, with regard to depression, the specific isoforms of CaMKIIs, as well as specific brain regions where this may function, have yet to be identified. Recent findings have revealed that βCaMKII is present in the lateral habenula, an area which serves as a key determinant for neuronal
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Pharmacological basis for the therapy of pain and inflammation with nonsteroidal anti inflammatory drugs

Pharmacological basis for the therapy of pain and inflammation with nonsteroidal anti inflammatory drugs

Another milestone was the discovery by Vane and co- workers that the analgesic, antipyretic and anti-inflamma- tory properties of acetylsalicylate were based on the inhibition of prostaglandin synthesis [4]. Vane showed that the acidic anti-inflammatory analgesics decreased pro- inflammatory prostaglandin concentrations by inhibiting cyclo-oxygenase. This finding made sense because the prostaglandins characterized in the 1960s were found to be substantially involved in bringing about and maintaining inflammatory processes by increasing vascular permeabil- ity and amplifying the effects of other inflammatory media- tors such as kinins, serotonin and histamine. Prostaglandin E 2 (PGE 2 ) is also involved in the induction of fever. As we now know, prostaglandins are not themselves significant mediators of pain; instead, they increase the sensitivity of nociceptors to other stimuli in traumatized tissue. They switch normally non-excitable polymodal receptors (‘silent nociceptors’) into a state in which they are easily excitable.
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EFFECT OF FICUS HISPIDA IN INFLAMMATORY BOWEL DISEASE IN EXPERIMENTAL ANIMALS

EFFECT OF FICUS HISPIDA IN INFLAMMATORY BOWEL DISEASE IN EXPERIMENTAL ANIMALS

The inflammatory response initiated by acetic acid includes activation of cyclo-oxygenase and lipooxygenase pathways.17 The FH treated rats showed a dose dependent decrease in macroscopi[r]

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Thromboxane A2 Mediates Augmented Polymorphonuclear Leukocyte Adhesiveness

Thromboxane A2 Mediates Augmented Polymorphonuclear Leukocyte Adhesiveness

polymorphonuclear leukocyte adherence, nor were they detected in significant quantities in supernates of polymorphonuclear leukocytes exposed to lipopolysaccharide. However, inhibitors of both cyclo-oxygenase and thromboxane synthetase reduced increases in adherence induced by arachidonic acid (10 µg/ml), suggesting that lipopolysaccharide- mediated increases in adherence were due to an arachidonic acid product other than prostaglandin E 2 or F 2 a. 8,11,14-Eicosatrienoic acid, a precursor of monoenoic prostaglandins, did not enhance polymorphonuclear leukocyte adhesiveness.

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Cells of the synovium in rheumatoid arthritis  Synovial fibroblasts

Cells of the synovium in rheumatoid arthritis Synovial fibroblasts

CCL = C-C motif ligand; COX = cyclo-oxygenase; CXCL = C-X-C motif ligand; DMARD = disease-modifying antirheumatic drug; FGF = fibroblast growth factor; FLIP = FLICE inhibitory protein; I[r]

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KINETIC ESTIMATION OF GABAPENTIN AND ETORICOXIB IN PHARMACEUTICALS

KINETIC ESTIMATION OF GABAPENTIN AND ETORICOXIB IN PHARMACEUTICALS

Etoricoxib 5‐chloro‐2‐[6‐methylpyridine‐3‐yl]‐3[4‐sulfonylphenyl]  pyridine) is a novel, selective second generation cyclo‐oxygenase‐ 2  inhibitor  administered  orally  as  an  analgesi[r]

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Developments in the scientific understanding of osteoarthritis

Developments in the scientific understanding of osteoarthritis

In recent population studies, genome-wide linkage scans have highlighted several specific genes involved in disease risk [15]. Chromosome 2q was positive in several scans, suggesting that this chromosome is likely to harbor one or more susceptibility genes. Two IL-1 genes (IL1 α and IL1 β ) and the gene encoding IL-1 receptor antagonist (IL1RN), located on chromosome 2q13 within a 430-kilobase genomic fragment, have been shown to associate with the development of primary knee, but not hip, OA [16]. IL1RN haplotype variants have also been shown to associate with radiographic severity of the OA [17]. Recently, a genome- wide association scan has identified a cyclo-oxygenase (COX)-2 variant involved in risk for knee OA [18]. These genetic associations of genes such as IL1 α , IL1 β , IL1RN, and COX2 underscore the potential role of inflammatory pathways in the pathogenesis of knee OA.
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Association of serum uric acid levels on birth weight, in women with hypertension in pregnancy: A retrospective cohort study

Association of serum uric acid levels on birth weight, in women with hypertension in pregnancy: A retrospective cohort study

ANNEXTURE I-ABBREVIATIONS ACOG American college of obstetrics and gynecology APH Antepartum hemorrhage BOH Bad obstetric history CHTN Chronic hypertension Cox -2 Cyclo-oxygenase 2 DBP Di[r]

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