Comparative study of anti-inflammatory and ulcerogenic activities of different cyclo-oxygenase inhibitors

Gambero, Alessandra; Becker, T; Zago, Andrea; Oliveira, Andréa Fermino de; Pedrazzoli, José

doi:10.1163/156856005774649377

Cited by 15 publications

(11 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…achieving an 80% inhibition of platelet COX-1 in vivo, considered as a COX-1 index [26], was ulcerogenic and inhibitory for gastric PGE 2 generation as well as ibuprofen, diclofenac and meloxicam. These results were in accordance with our previous report [14] and with others, showing that nimesulide at a dosage of 3 to 10 mg/kg did not affect PGE 2 formation in rat stomachs [27,28]. In contrast, the administration of 200 mg/kg of nimesulide by oral route, described by Laudanno et al [29], resulted in a nonulcerogenic response compared with animals receiving indomethacin by the same route.…”

Section: Controlsupporting

confidence: 93%

“…After 1 hr, the animals were treated with 1 ml of 100% ethanol or 1 ml of different NSAIDs (diclofenac, ibuprofen, meloxicam, nimesulide, or celecoxib) at two different doses. These doses were obtained from dose-response inhibitory curves, by evaluating PGE 2 production, as a COX-2 index, in the carrageenan-induced air pouch and TXB 2 production, as a COX-1 index, in peripheral blood, in vivo, as previously published [14]. Air pouches were induced by subcutaneous injection of 20 ml of sterile air into the dorsal skin of rats.…”

Section: Adaptive Cytoprotection Induced By 20% Ethanolmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Different Cyclooxygenase Inhibitors on Gastric Adaptive Cytoprotection Induced by 20% Ethanol

et al. 2007

Self Cite

View full text Add to dashboard Cite

In this study, we evaluated the effect of two different dosages of therapeutically prescribed nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen, diclofenac, nimesulide, meloxicam, and celecoxib (ED80 for COX-1 and COX-2) on normal gastric mucosa and mucosa, previously exposed to 20% ethanol. At COX-2-inhibiting dosages, the NSAIDs tested were nonulcerogenic, and the same response profile was observed in "adapted" stomachs. Interestingly, low doses of nimesulide and celecoxib increase the levels of Prostaglandin E(2) and COX-2, and protect against subsequent 100% ethanol exposition, suggesting that these drugs may act as "mild irritants" to gastric mucosa. The ulcerogenic response to NSAIDs was prevented by the previous 20% ethanol exposition, probably the result of nitric oxide synthesis, because PGE(2) levels in gastric mucosa were reduced by these agents and a concomitant nitric oxide blockade reversed this protection.

show abstract

Section: Controlsupporting

confidence: 93%

Section: Adaptive Cytoprotection Induced By 20% Ethanolmentioning

confidence: 99%

Effect of Different Cyclooxygenase Inhibitors on Gastric Adaptive Cytoprotection Induced by 20% Ethanol

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…Because DIC is a noxious agent affecting the mucosa [20], we believe that the increase in the HSP70 production was an adaptive response to the damaging effects of DIC, which is in accord with the findings of other studies showing that a variety of NSAIDs enhance the HSP70 expression in the gastric mucosa, in addition to their damaging effects [21, 22]. In study 2, we also found that GGA treatment significantly decreased the number of endoscopically detected gastric erosions and attenuated DNA injury in gastric mucosal cells, especially in the antrum.…”

Section: Discussionmentioning

confidence: 99%

“…The protective effect of GGA on the gastric mucosa against various NSAIDs has been reported in other studies. In a study performed by Ushijima et al [17], GGA prevented the disruption of the cell membrane integrity induced by a variety of NSAIDs; Gambero et al [20] found that it prevented the cellular injury induced by indomethacin in vitro, and Murakami et al [23] observed that GGA protected the rat gastric mucosa from aspirin-induced injury in vivo. Thus, it seems reasonable to assume that GGA will protect the human gastric mucosa against NSAIDs other than DIC, although such findings have not been specifically reported.…”

Section: Discussionmentioning

confidence: 99%

Geranylgeranylacetone Protects the Human Gastric Mucosa from Diclofenac-Induced Injury via Induction of Heat Shock Protein 70

et al. 2007

View full text Add to dashboard Cite

Background/Aim: Geranylgeranylacetone (GGA) enhances gastric mucosal protection against nonsteroidal anti-inflammatory drugs by upregulating mucosal heat shock proteins (HSP), but the effects of GGA on the human gastric mucosa have not been well examined. This study was conducted to determine whether a clinical dose of GGA protects the human gastric mucosa from diclofenac (DIC)-induced gastric mucosal injury. Methods: The study group comprised 40 healthy volunteers: 20 subjects were randomly assigned to take either placebo (lactose 1.5 g/day) or GGA (150 mg/day) for 2 weeks (study 1), and 20 subjects were assigned to take DIC (75 mg/day) plus placebo (lactose 1.5 g/day) or DIC (75 mg/day) plus GGA (150 mg/day) for 2 weeks (study 2). In both studies, gastroscopic biopsy specimens were obtained before and after treatment. Mucosal HSP70 expression and DNA damage were analyzed by measuring the levels of HSP70 and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-OHdG), respectively. Results: In study 1, GGA increased the mucosal HSP70 expression without increasing the 8-OHdG production. In study 2, DIC treatment increased the 8-OHdG production, whereas the combination of GGA and DIC enhanced the HSP70 expression and attenuated the increase in 8-OHdG induced by DIC. Conclusion: The clinical dose of GGA enhanced the gastric mucosal HSP70 expression and inhibited the DIC-induced gastric mucosal damage in humans.

show abstract

“…In humans, chronic administration of diclofenac for the treatment of various diseases such as rheumatoid and osteoarthritis induces gastric ulcer in 35%-60% of patients (9) . In general, NSAIDs are prescribed for its analgesic, antipyretic, and anti-inflammatory properties; its action is mediated by inhibition of the biosynthesis of prostaglandins, cyclooxygenase, and leukotriene (8,36) . They induce gastric mucosal lesions because of its acidic properties.…”

Section: Introductionmentioning

confidence: 99%

ADMINISTRATION OF H2 BLOCKERS IN NSAID INDUCED GASTROPATHY IN RATS: effect on histopathological changes in gastric, hepatic and renal tissues

Manocha

Lal

Venkataraman

2016

Arq. Gastroenterol.

View full text Add to dashboard Cite

-Background -Nonsteroidal anti-inflammatory drugs induces gastric mucosal lesions because of its acidic properties.Ranitidine, an H 2 receptor antagonist, has proved beneficial in patients with gastric ulcers. Objective -The present study was performed to assess the effect of administering ranitidine in Nonsteroidal anti-inflammatory drugs (diclofenac, nimesulide) induced gastropathy, and their effect on the histopathology of stomach, kidney and liver. Methods -Diclofenac, nimesulide, and ranitidine were administered in doses of 2, 4, and 6 mg/kg, p.o. once daily for 14 days, and their effect on gastric volume, acidity, mean ulcer number, and gastric pH. In addition, histopathological examination was also performed on sections of stomach, kidney and liver.Results -Following the administration of diclofenac or nimesulide, all the gastric parameters were significantly altered as well as the histopathology of stomach, liver and kidney. In the control group, the renal sections showed normal glomeruli with no thickening of glomerular basement membrane, while in diclofenac alone, nimesulide alone, and ranitidine with nimesulide groups, the thickening of glomerular basement membrane was observed. These alterations were observed to be reversed in the ranitidine with diclofenac group. In the sections from the liver, the control group showed anastomosing plates and cords of cuboidal hepatocytes with round well stained nuclei and abundant cytoplasm. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, mild dilatation of sinusoids is seen coupled with prominence of central vein. In the diclofenac alone and nimesulide alone groups, the proximal and distal convoluted tubules show mild focal tubular necrosis. In the gastric sections, the control group showed several folds forming villi, and the epithelial lining surface of the mucosa. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, the duodenum showed scattered inflammatory cells composed predominantly of lymphocytes. In diclofenac alone and nimesulide alone group, the sections from the gastric areas showed partial necrosis and mild chronic inflammation respectively. Conclusion -The study, therefore, has provided therapeutic rationale towards simultaneous administration of H 2 receptor blocker ranitidine with diclofenac to be more beneficial as compared to ranitidine with nimesulide, to minimise the gastric intolerance of diclofenac in long term treatment of inflammatory conditions. HEADINGS -Diclofenac. Ranitidine. Histamine H 2 antagonist. Stomach diseases. Non-steroidal anti-inflammatory agents.

show abstract

Comparative study of anti-inflammatory and ulcerogenic activities of different cyclo-oxygenase inhibitors

Cited by 15 publications

References 30 publications

Effect of Different Cyclooxygenase Inhibitors on Gastric Adaptive Cytoprotection Induced by 20% Ethanol

Effect of Different Cyclooxygenase Inhibitors on Gastric Adaptive Cytoprotection Induced by 20% Ethanol

Geranylgeranylacetone Protects the Human Gastric Mucosa from Diclofenac-Induced Injury via Induction of Heat Shock Protein 70

ADMINISTRATION OF H2 BLOCKERS IN NSAID INDUCED GASTROPATHY IN RATS: effect on histopathological changes in gastric, hepatic and renal tissues

Contact Info

Product

Resources

About