Effects of phenacetin and its metabolite p-phenetidine on COX-1 and COX-2 activities and expression in vitro

2003 ◽  
Vol 110 (5-6) ◽  
pp. 299-303 ◽  
Author(s):  
Esko Kankuri ◽  
Erkka Solatunturi ◽  
Heikki Vapaatalo
Keyword(s):  
Cox 2 ◽  
Cox 1

Cyclooxygenase-2 plays a significant role in regulating the tone of the fetal lamb ductus arteriosus

1999 ◽  
Vol 276 (3) ◽  
pp. R913-R921 ◽  
Author(s):  
Ronald I. Clyman ◽  
Pierre Hardy ◽  
Nahid Waleh ◽  
Yao Qi Chen ◽  
Françoise Mauray ◽  
...  
Keyword(s):  
Significant Role ◽  
Ductus Arteriosus ◽  
Late Gestation ◽  
Relative Contribution ◽  
Cox Inhibitor ◽  
Fetal Lamb ◽  
Cox 2 ◽  
Cox 2 Inhibitors ◽  
Cox 1

Nonselective cyclooxygenase (COX) inhibitors are potent tocolytic agents but have adverse effects on the fetal ductus arteriosus. We hypothesized that COX-2 inhibitors may not affect the ductus if the predominant COX isoform is COX-1. To examine this hypothesis, we used ductus arteriosus obtained from late-gestation fetal lambs. In contrast to our hypothesis, fetal lamb ductus arteriosus expressed both COX-1- and COX-2-immunoreactive protein (by Western analysis). Although COX-1 was found in both endothelial and smooth muscle cells, COX-2 was found only in the endothelial cells lining the ductus lumen (by immunohistochemistry). The relative contribution of COX-1 and COX-2 to PGE2 synthesis was consistent with the immunohistochemical results: in the intact ductus, PGE2 formation was catalyzed by both COX-1 and COX-2 in equivalent proportions; in the endothelium-denuded ductus, COX-2 no longer played a significant role in PGE2 synthesis. NS-398, a selective inhibitor of COX-2, was 66% as effective as the selective COX-1 inhibitor valeryl salicylate and the nonselective COX inhibitor indomethacin in causing contraction of the ductus in vitro. At this time, caution should be used when recommending COX-2 inhibitors for use in pregnant women.

scholarly journals Aktivitas Antiinflamasi Keladi Belau (Caladium bicolor (W. Ait) Vent.) Terhadap Enzim Siklooksigenase (COX) Secara In Vitro

2016 ◽  
Vol 3 ◽  
pp. 331-334
Author(s):  
Nisa Naspiah ◽  
Yoppi Iskandar ◽  
Moelyono M W Moelyono M W ◽  
Febrina Mahmudah ◽  
Lia Puspitasari
Keyword(s):  
Cox 2 ◽  
Cox 1

Penelitian mengenai aktivitas antiinflamasi keladi belau (Caladium bicolor (W. Ait) Vent.) terhadap enzim siklooksigenase (COX) secara in vitro telah dilakukan. Aktivitas antiinflamasi secara in vitro terhadap enzim COX ditentukan dengan menggunakan metode TMPD (N,N,N’,N’-tetrametil-p-fenilendiamin) secara spektrofotometri. Enzim COX yang diuji meliputi enzim COX-1 dan COX-2. Berdasarkan hasil pengujian diketahui ekstrak batang keladi belau mempunyai aktivitas antiinflamasi dengan nilai IC50 sebesar 250,66 ppm terhadap COX-1 dan 255,27 ppm terhadap COX-2. Hasil pengujian menunjukkan bahwa ekstrak tersebut lebih banyak menghambat enzim COX-1.

scholarly journals Cyclooxygenases Inhibitors Efficiently Induce Cardiomyogenesis in Human Pluripotent Stem Cells

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 554 ◽  
Author(s):  
Harshal Nemade ◽  
Aviseka Acharya ◽  
Umesh Chaudhari ◽  
Erastus Nembo ◽  
Filomain Nguemo ◽  
...  
Keyword(s):  
Wnt Signaling Pathway ◽  
Calcium Transient ◽  
Cardiac Differentiation ◽  
Cyclooxygenase Inhibitors ◽  
Cox Inhibitors ◽  
Screening Model ◽  
Cox 2 ◽  
Transient Measurements ◽  
Cox 1

Application of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is limited by the challenges in their efficient differentiation. Recently, the Wingless (Wnt) signaling pathway has emerged as the key regulator of cardiomyogenesis. In this study, we evaluated the effects of cyclooxygenase inhibitors on cardiac differentiation of hPSCs. Cardiac differentiation was performed by adherent monolayer based method using 4 hPSC lines (HES3, H9, IMR90, and ES4SKIN). The efficiency of cardiac differentiation was evaluated by flow cytometry and RT-qPCR. Generated hPSC-CMs were characterised using immunocytochemistry, electrophysiology, electron microscopy, and calcium transient measurements. Our data show that the COX inhibitors Sulindac and Diclofenac in combination with CHIR99021 (GSK-3 inhibitor) efficiently induce cardiac differentiation of hPSCs. In addition, inhibition of COX using siRNAs targeted towards COX-1 and/or COX-2 showed that inhibition of COX-2 alone or COX-1 and COX-2 in combination induce cardiomyogenesis in hPSCs within 12 days. Using IMR90-Wnt reporter line, we showed that inhibition of COX-2 led to downregulation of Wnt signalling activity in hPSCs. In conclusion, this study demonstrates that COX inhibition efficiently induced cardiogenesis via modulation of COX and Wnt pathway and the generated cardiomyocytes express cardiac-specific structural markers as well as exhibit typical calcium transients and action potentials. These cardiomyocytes also responded to cardiotoxicants and can be relevant as an in vitro cardiotoxicity screening model.

scholarly journals Intraluteal regulation of prostaglandin F2α-induced prostaglandin biosynthesis in pseudopregnant rabbits

Reproduction ◽  
2007 ◽  
Vol 133 (5) ◽  
pp. 1005-1016 ◽  
Author(s):  
M Zerani ◽  
C Dall’Aglio ◽  
M Maranesi ◽  
A Gobbetti ◽  
G Brecchia ◽  
...  
Keyword(s):  
Prostaglandin F2α ◽  
Enzymatic Activities ◽  
Synthesis Rate ◽  
Corpora Lutea ◽  
Positive Staining ◽  
Mrna Levels ◽  
Cox 2 ◽  
Pg E2 ◽  
Cox 1

The objective of the present study was to investigate in rabbit corpora lutea (CL), at both the cellular and molecular level, intraluteal cyclooxygenase (COX)-1, COX-2 and prostaglandin (PG) E2-9-ketoreductase (PGE2-9-K) enzymatic activities as well asin vitroPGE2 and PGF2α synthesis following PGF2α treatment at either early- (day-4) or mid-luteal (day-9) stage of pseudopregnancy. By immunohistochemistry, positive staining for COX-2 was localized in luteal and endothelial cells of stromal arteries at both the stages. In CL of both stages, basal COX-2 mRNA levels were poorly expressed, but rose (P< 0.01) 4- to 10-fold 1.5–6 h after treatment and then gradually decreased within 24 h. Compared to mid-stage, day-4 CL had lower (P< 0.01) COX-2 and PGE2-9-K basal activities, and PGF2α synthesis rate, but higher (P< 0.01) PGE2 production. Independent of luteal stage, PGF2α treatment did not affect COX-1 activity. In day-4 CL, PGF2α induced an increase (P< 0.01) in both COX-2 activity and PGF2α synthesis, whereas that of PGE2 remained unchanged. In day-9 CL, PGF2α up-regulated (P< 0.01) both COX-2 and PGE-9-K activities, and PGF2α production, but decreased (P< 0.01) PGE2 synthesis. All changes in gene expression and enzymatic activities occurred within 1.5 h after PGF2α challenge and were more marked in day-9 CL. Our data suggest that PGF2α directs intraluteal PG biosynthesis in mature CL, by affecting the CL biosynthetic machinery to increase the PGF2α synthesis in an auto-amplifying manner, with the activation of COX-2 and PGE-9-K; this may partly explain their differentially, age-dependent, luteolytic capacity to exogenous PGF2α in rabbits.

scholarly journals Are there attacking points in the eicosanoid cascade for chemotherapeutic options in benign meningiomas?

2007 ◽  
Vol 23 (4) ◽  
pp. E8 ◽  
Author(s):  
Christina Pfister ◽  
Rainer Ritz ◽  
Heike Pfrommer ◽  
Antje Bornemann ◽  
Marcos S. Tatagiba ◽  
...  
Keyword(s):  
World Health ◽  
Pcr Analysis ◽  
Prostaglandin E ◽  
Tissue Samples ◽  
Human Cortex ◽  
Normal Human ◽  
Cox 2 ◽  
Cox 1

Object The current treatment for recurrent or malignant meningiomas with adjuvant therapies has not been satisfactory, and there is an intense interest in evaluating new molecular markers to act as therapeutic targets. Enzymes of the arachidonic acid (AA) cascade such as cyclooxygenase (COX)–2 or 5-lipoxygenase (5-LO) are upregulated in a number of epithelial tumors, but to date there are hardly any data about the expression of these markers in meningiomas. To find possible targets for chemotherapeutic intervention, the authors evaluated the expression of AA derivatives at different molecular levels in meningiomas. Methods One hundred and twenty-four meningioma surgical specimens and normal human cortical tissue samples were immunohistochemically and cytochemically stained for COX-2, COX-1, 5-LO, and prostaglandin E receptor 4 (PTGER4). In addition, Western blot and polymerase chain reaction (PCR) analyses were performed to detect the presence of eicosanoids in vivo and in vitro. Results Sixty (63%) of 95 benign meningiomas, 21 (88%) of 24 atypical meningiomas, all five malignant meningiomas, and all normal human cortex samples displayed high COX-2 immunoreactivity. All cultured specimens and IOMM-Lee cells stained positive for COX-2, COX-1, 5-LO, and PTGER4. The PCR analysis demonstrated no changes in eicosanoid expression among meningiomas of different World Health Organization grades and in normal human cortical and dura mater tissue. Conclusions Eicosanoid derivatives COX-1, COX-2, 5-LO, and PTGER4 enzymes show a high universal expression in meningiomas but are not upregulated in normal human cortex and dura tissue. This finding of the ubiquitous presence of these enzymes in meningiomas offers an excellent baseline for testing upcoming chemotherapeutic treatments.

Role of prostaglandins in collecting duct-derived endothelin-1 regulation of blood pressure and water excretion

2007 ◽  
Vol 293 (6) ◽  
pp. F1805-F1810 ◽  
Author(s):  
Yuqiang Ge ◽  
Kevin A. Strait ◽  
Peter K. Stricklett ◽  
Tianxin Yang ◽  
Donald E. Kohan
Keyword(s):  
Blood Pressure ◽  
Collecting Duct ◽  
Urine Volume ◽  
Mrna Levels ◽  
Water Excretion ◽  
Salt Loading ◽  
Endothelin 1 ◽  
Cox 2 ◽  
Cox 1

Collecting duct (CD)-derived endothelin-1 (ET-1) exerts natriuretic, diuretic, and hypotensive effects. In vitro studies have implicated cyclooxygenase (COX) metabolites, and particularly PGE2, as important mediators of CD ET-1 effects. However, it is unknown whether PGE2 mediates CD-derived ET-1 actions in vivo. To test this, CD ET-1 knockout (KO) and control mice were studied. During normal salt and water intake, urinary PGE2 excretion was unexpectedly increased in CD ET-1 KO mice compared with controls. Salt loading markedly increased urinary PGE2 excretion in both groups of mice; however, the levels remained relatively higher in KO animals. Acutely isolated inner medullary collecting duct (IMCD) from KO mice also had increased PGE2 production. The increased IMCD PGE2 was COX-2 dependent, since NS-398 blocked all PGE2 production. However, increased CD ET-1 KO COX-2 protein or mRNA could not be detected in inner medulla or IMCD, respectively. Inner medullary COX-1 mRNA and protein levels and IMCD COX-1 mRNA levels were unaffected by Na intake or CD ET-1 KO. KO mice on a normal or high-Na diet had elevated blood pressure compared with controls; this difference was not altered by indomethacin or NS-398 treatment. However, indomethacin or NS-398 did increase urine osmolality and reduce urine volume in KO, but not control, animals. In summary, IMCD COX-2-dependent PGE2 production is increased in CD ET-1 KO mice, indicating that CD-derived ET-1 is not a primary regulator of IMCD PGE2. Furthermore, the increased PGE2 in CD ET-1 KO mice partly compensates for loss of ET-1 with respect to maintaining urinary water excretion, but not in blood pressure control.

scholarly journals Increased cyclooxygenase-2 expression and prostaglandin E2production in pressurized renal medullary interstitial cells

2010 ◽  
Vol 299 (3) ◽  
pp. R823-R831 ◽  
Author(s):  
Inge Carlsen ◽  
Kaitlin E. Donohue ◽  
Anja M. Jensen ◽  
Angela L. Selzer ◽  
Jie Chen ◽  
...  
Keyword(s):  
Mechanical Stress ◽  
Ureteral Obstruction ◽  
Interstitial Cells ◽  
Inflammatory Stress ◽  
Protein Levels ◽  
Cox 2 ◽  
Cox 1 ◽  
Expression And Activity

Renal medullary interstitial cells (RMICs) are subjected to osmotic, inflammatory, and mechanical stress as a result of ureteral obstruction, which may influence the expression and activity of cyclooxygenase type 2 (COX-2). Inflammatory stress strongly induces COX-2 in RMICs. To explore the direct effect of mechanical stress on the expression and activity of COX-2, cultured RMICs were subjected to varying amounts of pressure over time using a novel pressure apparatus. COX-2 mRNA and protein were induced following 60 mmHg pressure for 4 and 6 h, respectively. COX-1 mRNA and protein levels were unchanged. PGE2production in the RMICs was increased when cells were subjected to 60 mmHg pressure for 6 h and was prevented by a selective COX-2 inhibitor. Pharmacological inhibition indicating that pressure-induced COX-2 expression is dependent on p38 MAPK and biochemical knockdown experiments showed that NF-κB might be involved in the COX-2 induction by pressure. Importantly, terminal deoxyneucleotidyl transferase-mediated dUTP nick-end labeling and methylthiazoletetetrazolium assay studies showed that subjecting RMICs to 60 mmHg pressure for 6 h does not affect cell viability, apoptosis, and proliferation. To further examine the regulation of COX-2 in vivo, rats were subjected to unilateral ureteral obstruction (UUO) for 6 and 12 h. COX-2 mRNA and protein level was increased in inner medulla in response to 6- and 12-h UUO. COX-1 mRNA and protein levels were unchanged. These findings suggest that in vitro application of pressure recapitulates the effects on RMICs found after in vivo UUO. This directly implicates pressure as an important regulator of renal COX-2 expression.

scholarly journals The Medicinal Timber Canarium patentinervium Miq. (Burseraceae Kunth.) Is an Anti-Inflammatory Bioresource of Dual Inhibitors of Cyclooxygenase (COX) and 5-Lipoxygenase (5-LOX)

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
R. Mogana ◽  
K. Teng-Jin ◽  
C. Wiart
Keyword(s):  
Inflammatory Diseases ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
Frap Assay ◽  
Dual Inhibitor ◽  
Lead Compounds ◽  
Dual Inhibitors ◽  
Cox 2 ◽  
Cox 1

The barks and leaves extracts of Canarium patentinervium Miq. (Burseraceae Kunth.) were investigated for cyclooxygenase (COX) and 5-lipoxygenase (LOX) inhibition via in vitro models. The corresponding antioxidative power of the plant extract was also tested via nonenzyme and enzyme in vitro assays. The ethanolic extract of leaves inhibited the enzymatic activity of 5-LOX, COX-1, and COX-2 with IC50 equal to 49.66±0.02 μg/mL, 0.60±0.01 μg/mL, and 1.07±0.01 μg/mL, respectively, with selective COX-2 activity noted in ethanolic extract of barks with COX-1/COX-2 ratio of 1.22. The ethanol extract of barks confronted oxidation in the ABTS, DPPH, and FRAP assay with EC50 values equal to 0.93±0.01 μg/mL, 2.33±0.02 μg/mL, and 67.00±0.32 μg/mL, respectively, while the ethanol extract of leaves confronted oxidation in β-carotene bleaching assay and superoxide dismutase (SOD) assay with EC50 value of 6.04±0.02 μg/mL and IC50 value of 3.05±0.01 μg/mL. The ethanol extract acts as a dual inhibitor of LOX and COX enzymes with potent antioxidant capacity. The clinical significance of these data is quite clear that they support a role for Canarium patentinervium Miq. (Burseraceae Kunth.) as a source of lead compounds in the management of inflammatory diseases.

Targeting Mediators Of Chronic Inflammation: A Promising Alternative Therapeutic Use Of Plant-Derived Remedies With Potent Bioactivity And Lower Cytotoxicity

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S114-S115
Author(s):  
S Adebayo
Keyword(s):  
Medicinal Plants ◽  
Chronic Inflammation ◽  
Bioactive Molecules ◽  
Care Needs ◽  
Leaf Extracts ◽  
Promising Alternative ◽  
Cox 2 ◽  
Pharmacologically Active ◽  
Cox 1

Abstract Introduction/Objective Medicinal plants have a long history of use and has been exploited for basic health care needs for many centuries. The various parts of plants are rich sources of a plethora of pharmacologically active remedies that has remained largely unexplored for their therapeutic capabilities. Grewia mollis is one of the medicinal plants that are used to treat painful inflammatory conditions including rheumatism and associated fever. The inhibition of enzymes involved in prostaglandin (PG) synthesis are of great interest in combating chronic inflammation. Cyclooxygenases (COX) and Lipoxygenases (LOX), in particular COX-2 and 5-LOX utilize different pathways for PG synthesis and are important drivers of chronic inflammation. However, the use of conventional anti-inflammatory drugs and specific enzyme inhibitors against them are associated with severe adverse side-effects and organ toxicities. Therefore, attention has shifted to the search for potent and safer alternative strategies to treat chronic inflammation involving these mediators Methods The leaf part of G. mollis was extracted with solvents of varying polarities. The extracts were tested in vitro against COX-1, 2 and 5-LOX. In addition, the cytotoxicity and selectivity index of the plant extracts were evaluated using vero monkey kidney cells Results The hexane fraction of G. mollis leaf extracts had better inhibition against COX-1 (0,97±1,9 µg/mL) and COX-2 (1,13±0,2 µg/mL) when compared with the indomethacin control (1,30±0,6 µg/mL) and (1,52±0,2 µg/mL) respectively. Also, the butanol fraction inhibited 5-LOX (12,48±2,9 µg/mL) better than quercetin positive control (61,82±5,5 µg/mL). Overall, the extracts and fractions indicated reduced cytotoxicity (30,56-689,39 µg/mL) relative to the doxorubicin control (2,59 µg/mL). Conclusion The results indicated that extracts of G. mollis contained bioactive molecules capable of inhibiting the activities of C0X and 5-LOX with lower cytotoxicity. Pharmacologically active molecules with safety profile could be used, at least as a part of the template for remedies against mediators of chronic inflammation

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