Interaction between cyclooxygenase (COX)-1- and COX-2-products modulates COX-2 expression in the late phase of acute inflammation

Opioids confer biphasic (early and late) cardioprotection against myocardial infarction by opening mitochondrial ATP-sensitive K+ channels. It is unknown whether cyclooxygenase-2 (COX-2), which mediates ischemia-induced late preconditioning, also mediates opioid-induced cardioprotection. Isolated perfused rat hearts were subjected to 20 min of global ischemia followed by 20 min of reperfusion. BW-373U86 (BW), a δ-opioid receptor agonist, was administered 1, 12, or 24 h before death. Recovery of left ventricular developed pressure (LVDP) after ischemia-reperfusion improved when BW was administered 1 or 24 h before ischemia (control: 57 ± 8, BW 1 h: 75 ± 5, BW 24 h: 85 ± 6%) but not when it was administered 12 h before (60 ± 5%). Levels of 6-keto-PGF1α (a stable metabolite of PGI2) in coronary effluent after 20 min of reperfusion were higher with 24-h BW pretreatment than in controls (1,053 ± 92 vs. 724 ± 81 pg/ml), whereas 6-keto-PGF1α levels at baseline did not differ. Administration of a selective COX-2 inhibitor, NS-398, abolished the late phase of cardioprotection (recovery of LVDP, 53 ± 8%) and attenuated the increase in PGI2 (706 ± 138 pg/ml) but did not block the early phase of cardioprotection. The selective COX-1 inhibitor SC-560 did not affect either phase of protection. Western immunoblotting revealed upregulation of PGI2 synthase protein 24 h after BW administration without changes in COX-1 and COX-2 protein levels. In conclusion, the late (but not the early) phase of δ-opioid receptor-induced preconditioning is mediated by COX-2. A functional coupling between COX-2 and upregulated PGI2synthase appears to underlie this cardioprotective phenomenon in the rat.

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Contribution of Interaction between Nitric Oxide and Cyclooxygenases to the Production of Prostaglandins in Carrageenan-induced Inflammation

Anesthesiology ◽

10.1097/00000542-200410000-00025 ◽

2004 ◽

Vol 101 (4) ◽

pp. 983-990 ◽

Cited By ~ 42

Author(s):

Masaki Toriyabe ◽

Keiichi Omote ◽

Tomoyuki Kawamata ◽

Akiyoshi Namiki

Keyword(s):

Nitric Oxide ◽

Inflammatory Process ◽

Inflammatory Responses ◽

Late Phase ◽

Dialysis Catheter ◽

Microdialysis Probe ◽

Plantar Surface ◽

Ringer’S Solution ◽

Cox 2 ◽

Cox 1

Background Nitric oxide (NO) and prostaglandins (PGs) are crucial mediators contributing to generation of inflammatory responses and pain. This study was designed to investigate the effects of peripherally released NO on cyclooxygenase (COX) expression/activation and production of PGs in carrageenan-induced inflammation. Methods A microdialysis probe was implanted subcutaneously into the skin of hind paws of rats. The concentrations of NO metabolites, PGE2, and 6-keto-PGF1alpha (metabolite of PGI2) in the dialysate were measured. Carrageenan was injected into the plantar surface of the hind paw during perfusion of the dialysis catheter with modified Ringer's solution or N-monomethyl-L-arginine acetate. In addition, the effects of the selective COX-1 inhibitor SC-560 and the selective COX-2 inhibitor NS-398 on the production of NO, PGE2, and 6-keto-PGF1alpha were examined. Western blotting was performed to evaluate the expression of COX-1 and COX-2 in the skin at the site of the inflammation. Results Carrageenan injection resulted in increases in the concentrations of NO, PGE2, and PGI2, and these increases were completely suppressed by N-monomethyl-L-arginine acetate. SC-560 effectively inhibited the increase in PGE2 and PGI2 concentrations for the first 2 h, and NS-398 inhibited 3-6 h after carrageenan. Western blot analysis showed that the concentrations of both COX-1 and COX-2 in the skin increased after carrageenan. The up-regulation of COX-1 in the skin was observed 3 and 6 h after carrageenan and was not suppressed in the rats treated with N-monomethyl-L-arginine acetate. The up-regulation of COX-2 in the skin was also observed 3 and 6 h after carrageenan and was completely suppressed in the rats treated with N-monomethyl-L-arginine acetate. Conclusion The results of the current study suggest that NO activates COX-1 in the early phase of carrageenan and up-regulates COX-2 expression in the late phase in the skin, resulting in production of PGE2 and PGI2 at the site of inflammation, which would contribute to exacerbation of the inflammatory process.

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Expression of COX-1 and COX-2 in a Clinical Model of Acute Inflammation

Journal of Pain ◽

10.1016/j.jpain.2006.10.004 ◽

2007 ◽

Vol 8 (4) ◽

pp. 349-354 ◽

Cited By ~ 36

Author(s):

Asma A. Khan ◽

Michael Iadarola ◽

Hsiu-Ying T. Yang ◽

Raymond A. Dionne

Keyword(s):

Acute Inflammation ◽

Clinical Model ◽

Cox 2 ◽

Cox 1

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Design, Synthesis, Characterization and in silico molecular docking studies and in vivo anti-inflammatory Activity of Pyrazoline clubbed Thiazolinone Derivatives

Letters in Organic Chemistry ◽

10.2174/1570178617999201106113114 ◽

2020 ◽

Vol 17 ◽

Author(s):

Deepak Kumar Singh ◽

Mayank Kulshreshtha ◽

Yogesh Kumar ◽

Pooja A Chawla ◽

Akash Ved ◽

...

Keyword(s):

Molecular Docking ◽

Biological Activities ◽

Inflammatory Activity ◽

Standard Drug ◽

Docking Score ◽

Chemical Structures ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 1

Background: The pyrazolines give the reactions of aliphatic derivatives, resembling unsaturated compounds in their behavior towards permanganate and nascent hydrogen. This nucleus has been associated with various biological activities including inflammatory. Thiazolinone is a heterocyclic compound that contains both sulfur and nitrogen atom with a carbonyl group in their structure.Thiazolinone and their derivatives have attracted continuing interest because of their various biological activities, such as anti-inflammatory, antimicrobial, anti-proliferative, antiviral, anticonvulsant etc. The aim of the research was to club pyrazoline nucleus with thiazolinone in order to have significantanti-inflammatory activity. The synthesized compounds were chemically characterized for the establishment of their chemical structures and to evaluate as anti-inflammatory agent. Method: In the present work, eight derivatives of substituted pyrazoline (PT1-PT8) were synthesized by a three step reaction.The compounds were subjected to spectral analysis by Infrared, Mass and Nuclear magnetic resonance spectroscopy and elemental analysis data. All the synthesized were evaluated for their in vivo anti-inflammatory activity. The synthesized derivatives were evaluated for their affinity towards target COX-1 and COX-2, using indomethacin as the reference compound molecular docking visualization through AutoDock Vina. Results: Compounds PT-1, PT-3, PT-4 and PT-8 exhibited significant anti-inflammatory activity at 3rd hour being 50.7%, 54.3%, 52.3% and 57% respectively closer to that of the standard drug indomethacin (61.9%).From selected anti-inflammatory targets, the synthesized derivatives exhibited better interaction with COX-1 and COX-2 receptor, where indomethacin showed docking score of -6.5 kJ/mol, compound PT-1 exhibited highest docking score of -9.1 kJ/mol for COX-1 and compound PT-8 having docking score of 9.4 kJ/mol for COX-2. Conclusion: It was concluded that synthesized derivatives have more interaction with COX-2 receptors in comparison to the COX-1 receptors because the docking score with COX-2 receptors were very good. It is concluded that the synthesized derivatives (PT-1 to PT-8) are potent COX-2 inhibitors.

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COX-1 and COX-2 in Pain

Encyclopedia of Pain ◽

10.1007/978-3-540-29805-2_915 ◽

2006 ◽

pp. 483-485

Author(s):

Irmgard Tegeder

Keyword(s):

Cox 2 ◽

Cox 1

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Inflammatory response and matrix metalloproteinases in chronic kidney failure: Modulation by adropin and spexin

Experimental Biology and Medicine ◽

10.1177/15353702211012417 ◽

2021 ◽

pp. 153537022110124

Author(s):

Burak Yazgan ◽

Filiz Avcı ◽

Gülsün Memi ◽

Ebru Tastekin

Keyword(s):

Inflammatory Response ◽

Kidney Failure ◽

Renal Damage ◽

Urine Volume ◽

Kidney Tissue ◽

Public Health Problem ◽

Chronic Kidney Failure ◽

Urine Protein ◽

Cox 2 ◽

Cox 1

Chronic kidney disease is a major global public health problem. The peptide hormones adropin and spexin modulate many physiological functions such as energy balance and glucose, lipid and protein metabolism. However, it is unclear whether these peptides may exert effects on renal damage, tissue remodeling, and inflammatory conditions. In view of the limited information, we aimed to investigate the effect of adropin and spexin on matrix metalloproteinase and inflammatory response genes a rat model of adenine-induced chronic kidney failure. Chronic kidney failure was induced in rats by administering adenine hemisulfate. Renal function was determined in an autoanalyzer. Histopathological modifications were assessed by H&E staining. mRNA expression levels of ALOX 15, COX 1, COX 2, IL-1β, IL-10, IL-17A, IL-18 IL-21, IL-33, KIM-1, MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, NGAL, TGFβ1, TIMP-1, and TNFα in kidney tissue were measured by qPCR. Our results showed an increase of 24-h urine volume, serum creatinine, BUN, and urine protein levels in group with adenine-induced CKF. Adropin and spexin treatments decreased urine protein and 24-h urine volume. Renal damage, TIMP-1, IL-33, and MMP-2 increased after CKF induction, while COX 1, MMP-9, and MMP-13 levels were significantly reduced. Furthermore, KIM-1, TIMP-1, IL-33, and MMP-2 were downregulated by spexin treatment. Renal damage, NGAL, TIMP-1 IL-17A, IL-33, MMP-2, and MMP-3 decreased after adropin treatment, while MMP-13 levels were upregulated. Treatment with adropin+spexin decreased KIM-1, NGAL, TIMP-1, IL-1β, IL-17A, IL-18, IL-33, ALOX 15, COX 1, COX 2, TGFβ1, TNFα, MMP-2, MMP-3, and MMP-7, but increased MMP-13 levels. Our findings revealed that inflammatory response and MMP genes were modulated by adropin and spexin. These peptides may have protective effects on inflammation and chronic kidney damage progression.

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Differential expression of cyclooxygenase 1 and cyclooxygenase 2 in the bovine oviduct

Journal of Endocrinology ◽

10.1677/joe.1.06761 ◽

2006 ◽

Vol 191 (1) ◽

pp. 263-274 ◽

Cited By ~ 29

Author(s):

Simone Odau ◽

Christoph Gabler ◽

Christoph Holder ◽

Ralf Einspanier

Keyword(s):

Mrna Expression ◽

Estrous Cycle ◽

Luteal Phase ◽

Cellular Level ◽

Differential Distribution ◽

Cyclooxygenase 1 ◽

Epithelial Cell Layer ◽

Cox 2 ◽

Cycle Dependent ◽

Cox 1

The aim of the present study was to investigate the enzymes for the local prostaglandin (PG) biosynthesis present in the bovine oviduct during the estrous cycle to influence early reproductive events. Bovine oviducts were classified into four phases: pre-ovulatory, post-ovulatory, early-to-mid luteal, and late luteal phase, subdivided further into ipsi- or contralateral site and separated into ampulla or isthmus. Oviductal cells were gained by flushing the oviductal regions. Quantitative real-time reverse transcriptase-PCR was performed for the secretory and cytosolic phospholipases A2 (sPLA2IB, cPLA2α, and cPLA2β) and cyclooxygenases (COX-1 and COX-2) as the first step enzymes of PG synthesis. COX-1 and cPLA2β showed significant highest mRNA expression around and before ovulation compared with the luteal phase respectively. sPLA2IB and cPLA2α mRNA expression was unregulated during the estrous cycle. Regional differences in mRNA content were found for sPLA2IB with higher mRNA expression in the ampulla than in the isthmus. Western blot analysis revealed the highest COX-1 protein content in the early-to-mid luteal phase. Immunohistochemistry demonstrated that COX-1 was localized in epithelial and smooth muscle cells, whereas COX-2 was only localized in epithelial cells. COX-2 showed a differential distribution within the epithelial cell layer suggesting a regulation on a cellular level, although the COX-2 mRNA and protein amounts did not vary throughout the estrous cycle. A COX activity assay of oviductal cells revealed that COX activity originated predominantly from COX-1 than from COX-2. Treatment of primary oviductal cells with 10 pg/ml 17β-estradiol or 10 ng/ml progesterone resulted in a higher expression of COX-2 and cPLA2α, but not of the other enzymes. The expression pattern of these enzymes suggests that an estrous-cycle dependent and region-specific PG synthesis in the bovine oviduct may be required for a successful reproduction.

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Chiral Derivatives of Xanthones: Investigation of the Effect of Enantioselectivity on Inhibition of Cyclooxygenases (COX-1 and COX-2) and Binding Interaction with Human Serum Albumin

Pharmaceuticals ◽

10.3390/ph10020050 ◽

2017 ◽

Vol 10 (4) ◽

pp. 50 ◽

Cited By ~ 10

Author(s):

Carla Fernandes ◽

Andreia Palmeira ◽

Inês Ramos ◽

Carlos Carneiro ◽

Carlos Afonso ◽

...

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Binding Interaction ◽

Cox 2 ◽

Derivatives Of ◽

Cox 1

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The Renal Effects of NSAIDs in Dogs

Journal of the American Animal Hospital Association ◽

10.5326/jaaha-ms-6239 ◽

2015 ◽

Vol 51 (3) ◽

pp. 197-203 ◽

Cited By ~ 9

Author(s):

Amy L. Lomas ◽

Gregory F. Grauer

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Adverse Drug Events ◽

Important Species ◽

Federal Drug Administration ◽

Renal Effects ◽

Inflammatory Drugs ◽

Cox 2 ◽

Cox 1

The quality of life for dogs with osteoarthritis can often be improved with nonsteroidal anti-inflammatory drugs (NSAIDs); however, the number of adverse drug events associated with NSAID use reported to the Federal Drug Administration Center for Veterinary Medicine is higher than that for any other companion animal drug. Of those events, adverse renal reactions are the second most reported. NSAIDs produce pharmacologic effects via inhibition of cyclooxygenase (COX), which decreases production of prostanoids. Prostaglandins are synthesized by both the COX-1 and COX-2 enzymes in the healthy kidney and influence renal blood flow, glomerular filtration rate, renin release, and Na excretion. There are important species differences in the renal expression of COX-1 and COX-2. For example, dogs have higher basal levels of COX-2 expression in the kidney compared with humans. In addition, in dogs with chronic kidney disease, an increase in COX-2 expression occurs and synthesis of prostaglandins shifts to the COX-2 pathway. For those reasons, NSAIDs that target COX-2 may be expected to adversely affect renal function in dogs, especially dogs with chronic kidney disease. The purpose of this review was to evaluate the literature to report the renal effects of NSAIDs in dogs.

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