Effect of Cyclooxygenase-2 Inhibitor (Celecoxib) on the Infarcted Heart in situ

Yamamoto, Tohru; Kakar, Naseebullah; Vina, Ernest R.; Johnson, Paul E.; Bing, Richard J.

doi:10.1159/000056109

Cited by 9 publications

(5 citation statements)

References 20 publications

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“…These authors demonstrated that the relative risk of developing cardiovascular events was greater than with the nonselective COX inhibitor naproxen. These conclusions were confirmed by experimental evidence in infarcted heart muscle; here celecoxib (5 mg/kg) lowered the ratio of PGI 2 /thromboxane because of a diminished PGI 2 production [2,5]. In the present study, the average medullary values of the ratio PGI 2 /TXA 2 are lower for celecoxib than for aspirin (table 4), suggesting that, as in heart muscle, celecoxib tips the ratio PGI 2 /TXA 2 in favor of thromboxane.…”

Section: Resultssupporting

confidence: 87%

“…On the other hand, COX-2 inhibitors may predispose to thrombotic diseases, including myocardial infarction, and cause damage to the kidney [2,4]. In both heart and kidney, COX-2 inhibitors cause a decline in PGI 2 concentrations and a fall in the ratio prostacyclin/thromboxane [5,6]. In the current report, we compared the effects of Lomnicka/Karouni/Sue/Wessel/Bing …”

Section: Introductionmentioning

confidence: 97%

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Effects of Nonsteroidal Anti-Inflammatory Drugs on Prostacyclin and Thromboxane in the Kidney

Łomnicka

Karouni²,

Sue³

et al. 2003

Pharmacology

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Dose-response curves were obtained relating the effects of increasing amounts of aspirin, a nonselective cyclooxygenase (COX) inhibitor, and celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, on the concentrations of prostacyclin and thromboxane in renal cortex and medulla of rabbits. The concentrations of the two agonists (aspirin and celecoxib) which elicit a half-maximal response on the prostanoid concentration (EC₅₀) were compared. Additionally, controls for prostacyclin and thromboxane were related to values for the experimental groups. The EC₅₀ values for celecoxib were considerably lower than those for aspirin, indicating that celecoxib was more effective in suppressing prostanoid production. There were also significant differences between the majority of experimental groups and their respective controls, further evidence for the greater inhibitory activity of celecoxib on prostacyclin. Celecoxib lowered the ratio prostacyclin/thromboxane in the renal medulla; mercuric chloride further diminished the concentration of prostacyclin in the renal medulla. The results confirm that in the normal rabbit kidney, both nonselective and specific COX inhibitors interfere with renal prostanoid synthesis, but that a selective COX-2 inhibitor is more effective.

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Section: Resultssupporting

confidence: 87%

Section: Introductionmentioning

confidence: 97%

Effects of Nonsteroidal Anti-Inflammatory Drugs on Prostacyclin and Thromboxane in the Kidney

Łomnicka

Karouni²,

Sue³

et al. 2003

Pharmacology

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“…25 The effect of aspirin and celecoxib was previously described in the infarcted heart in situ. 27 Similar to the kidney, in the heart, aspirin did not change myocardial iNOS production and celecoxib lowered myocardial PGI 2 production but did not interfere with the induction of iNOS. 11 In summary, we have shown that both selective and nonselective COX-2 inhibitors cause a significant decline in prostacyclin and thromboxane in the renal medulla, whereas expression of COX-2 and iNOS remains unchanged.…”

Section: Inos and Cox-2mentioning

confidence: 88%

Nitric Oxide, Anti-Inflammatory Drugs on Renal Prostaglandins and Cyclooxygenase-2

Miyataka

Rich²,

Ingram³

et al. 2002

Hypertension

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Abstract-Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used as analgesics. They inhibit cyclooxygenases (COX), preventing the formation of prostaglandins, including prostacyclin and thromboxane. A serious side effect of COX-1 and COX-2 is renal damage. We report here that both a nonselective NSAID (aspirin, acetylsalicylic acid) and COX-2 selective NSAIDs (celecoxib and NS-398) diminished renal prostacyclin and thromboxane concentration in the renal medulla. NSAIDs failed to change COX-2 and iNOS (the inducible form of NO synthase) expression. A NO donor, B-NOD, preserved renal prostacyclin and thromboxane after administration of aspirin. PGI 2 and COX-2 protein were mainly expressed in the renal medulla, whereas iNOS expression was greater in the cortex. NSAIDs act by inhibition of cyclooxygenases. 2 Two isoforms of COX have been identified: cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). They are homodimers, heme-containing glycosylated proteins with 2 catalytic sites. 2 Aspirin, the classical nonselective NSAID, inhibits platelet thromboxane A2 formation through inhibition of COX-1; this forms the basis for the therapeutic and preventive effects in coronary artery disease.Inhibition of COX can cause severe gastric disturbances because of diminished prostacyclin synthesis in the gastric mucosa. 3 To overcome this side effect, selective COX-2 inhibitors, such as rofecoxib (VIOXX), celecoxib (Celebrex), and NS-398 have been developed. 2,4 These selective COX-2 inhibitors protect the gastric mucosa but, like nonselective COX inhibitors, cause renal damage, which is expressed as a reduction in glomerular filtration rate, renal blood flow, and diminished sodium and potassium excretion. 4 The decline in renal function is especially pronounced in the elderly and in patients with preexisting renal disease. 5 The renal effects are related to depletion of prostacyclin. 6 On the other hand, Wang et al 7 found that chronic administration of a selective COX-2 inhibitor decreased proteinuria and inhibited development of glomerular sclerosis in rats with reduced functional renal mass. The decrease in proteinuria was comparable to that seen with an ACE inhibitor. 7 Prostanoids result from the activity of cyclooxygenases on arachidonic acid. 2 Prostaglandins modulate renal microvascular hemodynamics, renin release, and tubular salt and water reabsorpotion. 8 Prostaglandins diminish vascular resistance in the renal vascular bed, increase perfusion, and mediate natriuretic processes; their presence maintains glomerular filtration rate. 9 Diminution of renal prostacyclin results in papillary necrosis or in interstitial nephritis. 9 Urinary sodium excretion is also reduced after application of celecoxib. 9 The role of COX-2 in the mammalian kidney has been thoroughly investigated. It was found that it is constitutionally expressed and that COX-2 mRNA is present at detectable concentrations in normal adult rat kidneys, particularly in microsomes, cortex, and papilla. Immunoreactivity of COX-2 mRNA was also loc...

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“…Therefore, Sal-B, the major functional component of S. miltiorrhiza Bge may be able to mediate the cardiovascular risk of celecoxib. The mechanism of celecoxib increasing cardiovascular risk is not clear, but there is some evidence that celecoxib might lower the production of prostacyclin without affecting the synthesis of thromboxane A 2 , contribution to a prothrombotic state (42). Sal-B exerts cardiovascular prevention via making balance with prostacyclin and thromboxane A 2 (43).…”

Section: Discussionmentioning

confidence: 99%

Combination Effects of Salvianolic Acid B with Low-Dose Celecoxib on Inhibition of Head and Neck Squamous Cell Carcinoma Growth In vitro and In vivo

Zhao

Hao

et al. 2010

Cancer Prevention Research

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Head and neck squamous cell carcinoma (HNSCC) development is closely associated with inflammation. Cyclooxygenase-2 (COX-2) is an important mediator of inflammation. Therefore, celecoxib, a selective inhibitor of COX-2, was hailed as a promising chemopreventive agent for HNSCC. Dose-dependent cardiac toxicity limits long-term use of celecoxib, but it seems likely that this may be diminished by lowering its dose. We found that salvianolic acid B (Sal-B), isolated from Salvia miltiorrhiza Bge, can effectively suppress COX-2 expression and induce apoptosis in a variety of cancer cell lines. In this study, we report that combination of Sal-B with low-dose celecoxib results in a more pronounced anticancer effect in HNSCC than either agent alone. The combination effects were assessed in four HNSCC cell lines (JHU-06, JHU-011, JHU-013, and JHU-022) by evaluating cell viability, proliferation, and tumor xenograft growth. Cell viability and proliferation were significantly inhibited by both the combined and single-agent treatments. However, the combination treatment significantly enhanced anticancer efficacy in JHU-013 and JHU-022 cell lines compared with the single treatment regimens. A half-dose of daily Sal-B (40 mg/kg/d) and celecoxib (2.5 mg/kg/d) significantly inhibited JHU-013 xenograft growth relative to mice treated with a full dose of Sal-B or celecoxib alone. The combination was associated with profound inhibition of COX-2 and enhanced induction of apoptosis. Taken together, these results strongly suggest that combination of Sal-B, a multifunctional anticancer agent, with low-dose celecoxib holds potential as a new preventive strategy in targeting inflammatory-associated tumor development. Cancer Prev Res; 3(6); 787-96. ©2010 AACR.

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Effect of Cyclooxygenase-2 Inhibitor (Celecoxib) on the Infarcted Heart in situ

Cited by 9 publications

References 20 publications

Effects of Nonsteroidal Anti-Inflammatory Drugs on Prostacyclin and Thromboxane in the Kidney

Effects of Nonsteroidal Anti-Inflammatory Drugs on Prostacyclin and Thromboxane in the Kidney

Nitric Oxide, Anti-Inflammatory Drugs on Renal Prostaglandins and Cyclooxygenase-2

Combination Effects of Salvianolic Acid B with Low-Dose Celecoxib on Inhibition of Head and Neck Squamous Cell Carcinoma Growth In vitro and In vivo

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