Influence of simultaneous inhibition of cyclooxygenase-2 and inducible nitric oxide synthase in experimental colitis in rats

被引：49
作者：
Dudhgaonkar S.P. [1 ]
Tandan S.K. [1 ]
Kumar D. [1 ]
Raviprakash V. [1 ]
Kataria M. [2 ]
机构：
[1] Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Dist. - Bareilly, 243 122, U.P., Izatnagar
[2] Division of Biochemistry, Indian Veterinary Research Institute, U.P. - 243 122, Izatnagar
来源：
Inflammopharmacology | 2007年 / 15卷 / 5期
关键词：
Colitis; COX-2; Inflammation; iNOS; Interaction; Rats;
D O I：
10.1007/s10787-007-1603-3
中图分类号：
学科分类号：
摘要：
The inflamed mucosa in ulcerative colitis produces high amount of prostaglandin (PG) and nitric oxide (NO) through inducible enzymes: cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), respectively, implicating them as potential anti-inflammatory drug targets. COX-2 or iNOS-related treatments in different models of colitis have yielded ambiguous results ranging from exacerbation of disease to abolition of inflammation. iNOS and COX-2 induction is blocked by potent anti-inflammatory glucocorticoids, however, serious side effects including relapses limit their usefulness in colitis for long time. Simultaneous inhibition of iNOS and COX-2 was investigated in the current study in 2, 4, 6 trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. Treatment group received rofecoxib, aminoguanidine hydrochloride or their combination at different doses at 48, 36, 24, 12 and 1 h prior to induction of colitis and 12 h later. Colonic myeloperoxidase (MPO), COX-2, nitrate and nitrite, tumor necrosis factor-α (TNF-α) and lipid peroxidation were maximally reduced by combination of 10 mg/kg rofecoxib and 30 mg/kg of aminoguanidine hydrochloride in TNBS-induced colitis in rats. However, maximum increase in SOD and catalase was noted by this combination. Rats treated with rofecoxib, aminoguanidine hydrochloride and their combinations reduced the inflammation, acute colonic damage produced by TNBS as verified by macroscopic changes in colon. Combination of rofecoxib (10 mg/kg) and aminoguanidine hydrochloride (30 mg/kg) has maximal protective effect on colonic injury induced by TNBS enema which is probably, via mechanism of local inhibition of iNOS and COX-2 activity in colonic mucosa and support the idea that simultaneous inhibition of iNOS and COX-2 inhibitors have a promising potential in the treatment of colitis. © 2007 Birkhäuser Verlag.
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页码：188 / 195
页数：7
相关论文
共 61 条
[1]  
Ademoglu E., Erbil Y., Tam B., Et al., Do vitamin E and selenium have beneficial effects on trinitrobenzenesulfonic acid-induced experimental colitis?, Dig. Dis. Sci, 49, pp. 102-108, (2004)
[2]  
Aebi H.E., Catalase, Methods of Enzymatic Analysis, pp. 273-285, (1983)
[3]  
Ajuebor M.N., Singh A., Wallace J.L., Cyclooxygenase-2-derived prostaglandin D(2) is an early anti-inflammatory signal in experimental colitis, Am. J. Physiol. - Gastrointest. Liver Physiol, 279, (2000)
[4]  
Alderton W.K., Cooper C.E., Knowles R.G., Nitric oxide synthases: Structure, function and inhibition, Biochem. J, 357, pp. 593-615, (2001)
[5]  
Carty E., De Brabander M., Feakin R.M., Et al., Measurement of in vivo rectal mucosal cytokine and eicosanoid production in ulcerative colitis using filter paper, Gut, 46, pp. 487-492, (2000)
[6]  
Cetinkaya A., Bulbuloglu E., Kurutas E.B., Et al., Beneficial effects of N-acetylcysteine on acetic acid-induced colitis in rats, Tohoku J. Exp. Med, 206, pp. 131-139, (2005)
[7]  
Cosme R., Lublin D., Takafuji V., Et al., Prostanoids in human colonic mucosa: Effects of inflammation on PGE(2) receptor expression, Hum. Immunol, 61, pp. 684-696, (2000)
[8]  
Cuzzocrea S., Mazzon E., Serraino I., Et al., Celecoxib, a selective cyclo-oxygenase-2 inhibitor reduces the severity of experimental colitis induced by dinitrobenzene sulfonic acid in rats, Eur. J. Pharmacol, 431, pp. 91-102, (2001)
[9]  
Dieter P., Hempel U., Kamionka S., Et al., Prostaglandin E2 affects differently the release of inflammatory mediators from resident macrophages by LPS and muramyl tripeptides, Mediators Inflamm, 8, pp. 295-303, (1999)
[10]  
Dijkstra G., Moshage H., van Dullemen H.M., Et al., Expression of nitric oxide synthases and formation of nitrotyrosine and reactive oxygen species in inflammatory bowel disease, J. Pathol, 186, pp. 416-421, (1998)
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