Roles of Enterobacteria, Nitric Oxide and Neutrophil in Pathogenesis of Indomethacin-Induced Small Intestinal Lesions in Rats

Konaka, Akira; Kato, Shinichi; Tanaka, Akiko; Kunikata, Tomonori; Korolkiewicz, Roman; Takeuchi, Koji

doi:10.1006/phrs.1999.0550

Cited by 145 publications

(211 citation statements)

References 30 publications

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“…This is in agreement with the earlier reports that have administered NSAIDs and observed severe hepatotoxicity and intestinal damage in the rat small intestine that was evident both macroscopically and histologically, resulting in loss of surface epithelium, mucosal necrosis and massive inflammatory cell infiltration (14,25,30,35,36) . Previous studies have reported that NSAIDs may also induce gastric damage by acid-independent mechanisms such as by increasing oxidative stress parameters viz.…”

Section: • Change In Phsupporting

confidence: 93%

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.

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-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.

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Section: • Change In Phsupporting

confidence: 93%

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.

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“…30) In addition, Whittle et al 11) and Konaka et al 12) further showed that the excessive NO via iNOS may also play a key pathogenic role in the ulcerogenic response. Tanaka et al 31) also reported that the oral administration of aminoguanidine, a selective inhibitor of iNOS, prevented the development of IMC-induced intestinal ulcerogenic lesions in AA rats.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7] On the other hand, a number of elements, such as inducible nitric oxide synthase (iNOS), bacterial flora and neutrophils are also involved in the pathogenesis of intestinal ulceration induced by NSAIDs. [8][9][10][11][12] In particularly, the presence of enterobacteria is essential for NSAID-induced ulceration to occur in the small intestine. 10,11) Previously reports show that the excessive production of nitric oxide (NO) plays a key pathogenic role in the intestinal ulcerogenic response to indomethacin (IMC) in model rats for RA, and the number of intestinal ulcerogenic lesions increases with the increasing oral dose.…”

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confidence: 99%

Excessive Interleukin 18 Relate the Aggravation of Indomethacin-Induced Intestinal Ulcerogenic Lesions in Adjuvant-Induced Arthritis Rat

Nagai

Tanino

Ito

2015

Biological & Pharmaceutical Bulletin

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It is well known that rheumatoid arthritis patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) are more susceptible to NSAIDs-induced gastroenteropathy in comparison with other patients. In this study we demonstrate that expression levels of interleukin (IL)-18 are related to aggravation of intestinal ulcerogenic lesions in adjuvant-induced arthritis (AA) rats following oral administration of indomethacin. AA rats were administered oral indomethacin (40 mg/kg) and killed under deep isoflurane anesthesia after 24 h. The small intestinal mucosa was then examined. Oral administration of indomethacin caused hemorrhagic lesions in the small intestinal mucosa of AA rats, and the lesion score of AA rats 24 h after indomethacin treatment was approximately 5.6-fold higher than for normal rats administered indomethacin. IL-18 expression in the small intestinal mucosa of AA rats administered indomethacin was also higher in comparison with normal rats receiving indomethacin. In addition, interferon-γ and nitric oxide levels in the small intestinal mucosa of AA rats were increased following oral administration of indomethacin. It is possible that IL-18 expression in AA rats renders the small intestinal mucosa more sensitive to indomethacin, and that IL-18 may play a role in aggravating intestinal ulcerogenic lesions in AA rats treated with this drug.

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“…MPO is an essential enzyme for PMNs function and a useful indicator of its infiltration. Evidence indicates that normal small intestine bears a low background of MPO activity, and the enzyme activity increased significantly in ischemic small intestine followed by PMNs infiltration [48,49] . MPO activity also increased in the lung of rats with acute pancreatitis [50,51] .…”

Section: Discussionmentioning

confidence: 99%

Epidermal growth factor prevents gut atrophy and maintains intestinal integrity in rats with acute pancreatitis

Chen¹

2000

WJG

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Roles of Enterobacteria, Nitric Oxide and Neutrophil in Pathogenesis of Indomethacin-Induced Small Intestinal Lesions in Rats

Cited by 145 publications

References 30 publications

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

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

Excessive Interleukin 18 Relate the Aggravation of Indomethacin-Induced Intestinal Ulcerogenic Lesions in Adjuvant-Induced Arthritis Rat

Epidermal growth factor prevents gut atrophy and maintains intestinal integrity in rats with acute pancreatitis

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