Determination of expression of cyclooxygenase-1 and -2 isozymes in canine tissues and their differential sensitivity to nonsteroidal anti-inflammatory drugs

Wilson, Joel E.; Chandrasekharan, N.V.; Westover, Kenneth D.; Eager, Kendra B.; Simmons, Denise R.

doi:10.2460/ajvr.2004.65.810

Cited by 77 publications

(58 citation statements)

References 21 publications

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“…The cell-free supernatant was collected and stored for analysis. To evaluate the effects of NSAIDs and DEX on canine BMCMCs in response to chemical challenge, BMCMCs were treated with various NSAIDs or DEX in the Tyrode’s salt solution at the concentrations indicated in Table 2 for 1 h. The concentrations of carprofen, deracoxib and piroxicam were chosen based on previous canine whole blood assays of these NSAIDs (McCann et al, 2004; Wilson et al, 2004). NGDA at 2 μM has previously been used to inhibit LOX activity in RBL cells (Glitsch et al, 2002).…”

Section: Methodsmentioning

confidence: 99%

Characterization and modulation of canine mast cell derived eicosanoids

Lin

London

2010

Veterinary Immunology and Immunopathology

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Mast cells play an important role in both innate and acquired immunity as well as several pathological conditions including allergy, arthritis and neoplasia. They influence these processes by producing a variety of mediators including cytokines, chemokines and eicosanoids. Very little is currently known about the spectrum of inflammatory mediators, particularly eicosanoids (prostaglandins and leukotrienes), produced by canine mast cells. This is important since modulating mast cell derived eicosanoids may help in the treatment of autoimmune and inflammatory disorders. The purpose of this study was to investigate the spectrum of eicosanoids produced by normal canine mast cells and to evaluate the effects of cytokines and non-steroidal anti-inflammatory mediators (NSAIDS) on eicosanoid production and release. Canine bone marrow derived cultured mast cells (cBMCMCs) expressed COX-1, COX-2, and 5-LOX and synthesized and released PGD2, PGE2, LTB4, and LTC4 following activation by a variety of stimuli. The selective COX-2 NSAIDs carprofen (Rimadyl®) and deracoxib (Deramaxx®) inhibited PGD2 and PGE2 production but only slightly inhibited LTB4 and LTC4. The mixed COX-1/COX-2 inhibitor piroxicam blocked PGD2 and PGE2 production, but upregulated LTC4 following treatment while tepoxilan (Zubrin®), a pan COX/LOX inhibitor, markedly reduced the production of all eicosanoids. The LOX inhibitor nordihydroguaiaretic acid (NDGA) prevented LTB4/LTC4 release and BMBMC degranulation. Pre-incubation of cBMCMCs with IL-4 and SCF sensitized these cells to degranulation in response to substance P. In conclusion, canine BMCMCs produce an array of eicosanoids similar to those produced by mast cells from other species. Tepoxilan appeared to be the most effective NSAID for blocking eicosanoid production and thus may be useful for modulating mast cell mediated responses in dogs.

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Section: Methodsmentioning

confidence: 99%

Characterization and modulation of canine mast cell derived eicosanoids

Lin

London

2010

Veterinary Immunology and Immunopathology

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“…15 Additionally, no data are available on mRNA or protein concentrations for COX isoforms in the laminae in horses with acute clinical laminitis.…”

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confidence: 99%

Cyclooxygenase Expression in The Early Stages of Equine Laminitis: A Cytologic Study

Blikslager¹,

Yin²,

Cochran³

et al. 2006

J Vet Int Med

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Background: Recent reports indicate increased amounts of mRNA from inflammation-related genes in the prodromal stage of laminitis.Hypothesis: Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) undergo distinct patterns of expression in equine laminae in the developmental stage (DEV) and acute clinical stage (LAM) of laminitis.Animals: Horses selected from an outbred population were placed into 1 of 4 groups: DEV (n 5 5), CON-3h (control group for DEV, n 5 5), LAM (n 5 5) and CON-10h (control group for LAM, n 5 5).Methods: Laminar and skin samples were obtained from (1) animals either undergoing leukopenia (DEV) or the onset of clinical signs of laminitis (LAM) after black walnut extract (BWE) administration and (2) animals either 3 (CON-3h ) or 10 (CON-10h) hours after administration of water. Real-time quantitative polymerase chain reaction (RT-qPCR), immunoblotting, and immunohistochemical analysis were performed for COX-1 and COX-2.Results: Upon immunohistochemical analysis of all 4 groups, COX-2 was expressed by most viable epithelial cells in both laminae and skin. COX-1 exhibited similar epithelial expression to COX-2 in skin epidermis, but was expressed exclusively in the basal layer of laminar epidermis. COX-1 protein was not detectable in dermal vasculature of equine skin or laminae, whereas COX-2 was present in endothelial and vascular smooth muscle cells of dermal vasculature in both skin and laminae in all groups. A marked increase in laminar COX-2 protein concentrations was detected on immunoblotting in the DEV group, although a lesser increase was observed in the LAM group.Conclusions and Clinical Importance: COX-2 protein expression is markedly increased in the resident laminar cell types in the developmental stage of BWE-induced laminitis.

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“…It is a preferential COX-2 inhibitor. The ratio of selective inhibition of COX-1 to COX-2 declared by the manufacturer (Rimadyl ® , tablets for dogs) is at least 1 : 3 (Ricketts et al 1998;KayMugford et al 2000;Wilson et al 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Both COX-1 expression and relative COX-1/COX-2 are higher in some animal species (including dogs and rats) in comparison with humans, and this fact may partially explain the sensitivity of these species to even low NSAID doses (Table 1) (Wilson et al 2004;Radi and Khan 2006). COX-2 expression in the colon in the dog has attracted special attention.…”

Section: Discussionmentioning

confidence: 99%

Effect of selected non-steroidal anti-inflammatory drugs on the pathomorphology of the mucous membrane of the canine colon

Szweda¹,

Szarek²,

Dublan³

et al. 2013

Vet. Med. - Czech

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Non-steroidal anti-inflammatory drugs (NSAIDs) have been commonly used for the management of chronic pain caused by inflammatory joint disease in dogs. Although effective at relieving pain and inflammation, NSAIDs are associated with a significant risk of serious gastrointestinal side effects. The present study was therefore designed to investigate the effects of carprofen as a poorly-selective COX (cyclooxygenase) inhibitor and robenacoxib as a selective COX-2 inhibitor on the colon mucosa. A biopsy of the gastrointestinal tract was performed before treatment and on the last day of treatment with orally-administered carprofen (Group I), robenacoxib (Group II) and empty gelatine capsule (Group III) for twenty-one days in a randomised study. The most evident microscopic lesions in the colonic mucosa in young beagles were caused by a 21-day treatment with robenacoxib. The infiltration with inflammatory cells in the lamina propria of the colonic mucosa was the most commonly-found histopathological lesion.Keywords: carprofen; robenacoxib; cyclooxygenase; beagle; gastrointestinal tract; inflammatory cells List of abbrevationsARI = absolute risk increase, BM = body mass, CBC = complete blood count, COX = cyclooxygenase, GI = gastrointestinal, IC 50 = half maximal inhibitory concentration, NSAIDs = non-steriodal anti-inflammatory drugs, PGE 2 = prostaglandin, PGI 2 = prostacyclin

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Determination of expression of cyclooxygenase-1 and -2 isozymes in canine tissues and their differential sensitivity to nonsteroidal anti-inflammatory drugs

Cited by 77 publications

References 21 publications

Characterization and modulation of canine mast cell derived eicosanoids

Characterization and modulation of canine mast cell derived eicosanoids

Cyclooxygenase Expression in The Early Stages of Equine Laminitis: A Cytologic Study

Effect of selected non-steroidal anti-inflammatory drugs on the pathomorphology of the mucous membrane of the canine colon

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