Inhibition of both COX-1 and COX-2 is required for development of gastric damage in response to nonsteroidal antiinflammatory drugs

Tanaka, Akiko; Araki, Hideo; Komoike, Yusaku; Hase, Shoko; Takeuchi, Koji

doi:10.1016/s0928-4257(01)00005-5

Cited by 143 publications

(124 citation statements)

References 20 publications

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“…The dosage of ketoprofen used in the present study was 0.25 mg/ kg; we have previously reported that ketoprofen alone at a reduced dosage had caused mild to moderate gastric mucosal injuries, such as invasive erosions, without clinical signs in healthy dogs [31]. Tanaka et al have also reported that the gastric ulcerogenic property of NSAIDs cannot be accounted for solely by COX-1 inhibition; it requires the inhibition of both COX-1 and COX-2 [39]. One dog in the NC group exhibited the weakly positive fecal blood, and had small mucosal erosion in the pyloric antrum.…”

Section: Disccusionmentioning

confidence: 71%

The Interaction between Orally Administered Non-Steroidal Anti-Inflammatory Drugs and Prednisolone in Healthy Dogs

Narita

Sato

Motoishi

et al. 2007

The Journal of Veterinary Medical Science

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ABSTRACT. The interaction between oral non-steroidal anti-inflammatory drugs (NSAIDs) and prednisolone administered concurrently for 30 days was studied in 18 healthy dogs divided into 3 groups of 6 dogs each: a drug-free negative control group (NC group) given 2 gelatin capsules; a group given meloxicam (0.1 mg/kg) and prednisolone (0.5 mg/kg) (MP group); and a group given a reduced dosage of ketoprofen (0.25 mg/kg, PO) and prednisolone (0.5 mg/kg, PO) (KP group). The dogs were periodically monitored by physical examinations, blood analyses, endoscopic examinations, fecal occult blood tests, renal function tests [effective renal plasma flow (ERPF) and glomerular filtration rate (GFR)], urinalyses [urinary sediments, and urinary micro-albumin to creatinine ratio (UAlb/Cre)], urinary enzyme indices, and haemostatic function tests [buccal mucosa bleeding time (BMBT), cuticle bleeding time (CBT)]. Significant changes were observed in the KP group, including a decrease of ERPF and GFR, an increased UAlb/Cre ratio, prolonged BMBT and CBT, as well as the presence of more severe grades of endoscopic lesions and fecal occult blood. In both the MP and KP groups, abnormal enzymuria with exfoliation of renal tubular epithelial cells in the urine was found. However, no significant changes in any of the other tests were observed in the MP group compared with the NC group. These findings suggest that the combination of NSAIDs, even selective COX-2 inhibitors, with prednisolone may be contraindicated due to the potential for serious adverse effects on the kidneys, the platelets, and the gastrointestinal tract.

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Section: Disccusionmentioning

confidence: 71%

The Interaction between Orally Administered Non-Steroidal Anti-Inflammatory Drugs and Prednisolone in Healthy Dogs

Narita

Sato

Motoishi

et al. 2007

The Journal of Veterinary Medical Science

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“…These observations indicate that, in contrast to the initial concept, COX-2 plays an important role in gastric mucosal defense. Accordingly to this, experimental studies have reported that inhibition of both COX-1 and COX-2 is required for NSAID-induced gastric injury Tanaka et al, 2001;Peskar et al, 2001) and therefore Coxibs markedly decrease but do not eliminate NSAIDs associated gastric and duodenal ulceration (Silverstein et al, 2000;Sostres et al, 2010). In fact, indomethacin and similar NSAIDs, which inhibit both isoforms of the COX enzyme, produce more severe damage in gastric tissue, even gastrointestinal bleeding, than more selective drugs (Delaney et al, 2007).…”

Section: Non-steroidal Anti-inflammatory Drugs (Nsaids)mentioning

confidence: 98%

Gastric Ulcer Etiology

Silva¹,

Sousa²

2011

Peptic Ulcer Disease

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“…10 min before L-NAME treatment. The histamine H 1 -receptor antagonist tripelennamine (Sigma), the nonselective cyclooxygenase inhibitors indomethacin (Sigma) and diclofenac (Sigma) (20,21), as well as 16,16-dimethyl prostaglandin E 2 (dm-PGE 2 ) (Cayman, Ann Arbor, MI, USA) were all administered (s.c.) 1 h before partial gastric vascular occlusion (22). The cyclooxynase (COX)-2 inhibitor rofecoxib (21,23) and the COX-1 inhibitor SC-560 (21,24), suspended in 0.5% CMC, were administered p.o.…”

Section: Agentsmentioning

confidence: 99%

On the Mechanisms Underlying Histamine Induction of Gastric Mucosal Lesions in Rats With Partial Gastric Vascular Occlusion

Amagase

Okabe

2003

J Pharmacol Sci

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Abstract. Although it is well known that histamine induces gastric mucosal lesions in laboratory animals, the fundamental mechanisms remain unclear. In order to further analyze the vascular mechanisms underlying histamine-induced lesions, a new model was developed in the glandular stomach via administration of histamine (40 mg / kg, s.c.) twice to rats with partial gastric vascular occlusion (ligated left gastric artery and vein) also subjected to pylorus ligation. Both antagonists of histamine H 2 -receptors (roxatidine and famotidine) and H 1 -receptors (epinastine and tripelennamine) significantly inhibited lesion formation at doses that did not inhibit acid secretion. Combined treatment of tripelennamine and famotidine synergistically inhibited lesion formation. Nitro L-arginine methyl ester inhibited lesion development; inhibition was reversed by concomitantly administered L-arginine. Indomethacin, diclofenac, and SC-560 (a selective COX-1 inhibitor), but not rofecoxib (a selective COX-2 inhibitor), significantly inhibited lesion formation. In addition, sodium bicarbonate, pirenzepine, S-0509 (a gastrin / CCK 2 inhibitor), omeprazole, sucralfate, and a prostaglandin analog also significantly inhibited lesion formation. It was concluded that the mechanism by which histamine induces gastric lesions in rats with partial gastric vascular occlusion appears to involve extensive vasodilation resulting from histamine acting on microvasculature histamine H 1 -and H 2 -receptors, generation of endogenous nitric oxide and prostaglandins, with the presence of gastric acid.

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Inhibition of both COX-1 and COX-2 is required for development of gastric damage in response to nonsteroidal antiinflammatory drugs

Cited by 143 publications

References 20 publications

The Interaction between Orally Administered Non-Steroidal Anti-Inflammatory Drugs and Prednisolone in Healthy Dogs

The Interaction between Orally Administered Non-Steroidal Anti-Inflammatory Drugs and Prednisolone in Healthy Dogs

Gastric Ulcer Etiology

On the Mechanisms Underlying Histamine Induction of Gastric Mucosal Lesions in Rats With Partial Gastric Vascular Occlusion

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