INDUCTION OF NITRIC-OXIDE SYNTHASE IN-VIVO AND CELL INJURY IN RAT DUODENAL EPITHELIUM BY A WATER-SOLUBLE EXTRACT OF HELICOBACTER-PYLORI

Citation
D. Lamarque et al., INDUCTION OF NITRIC-OXIDE SYNTHASE IN-VIVO AND CELL INJURY IN RAT DUODENAL EPITHELIUM BY A WATER-SOLUBLE EXTRACT OF HELICOBACTER-PYLORI, British Journal of Pharmacology, 123(6), 1998, pp. 1073-1078
Citations number
35
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00071188
Volume
123
Issue
6
Year of publication
1998
Pages
1073 - 1078
Database
ISI
SICI code
0007-1188(1998)123:6<1073:IONSIA>2.0.ZU;2-9
Abstract
1 Helicobacter pylori (Hp) infection, which involves the gastric antru m and duodenal mucosa, may be involved in peptic ulceration by stimula ting the local release of cytoxic or pro-inflammatory factors. 2 Nitri c oxide (NO) is known to be cytotoxic at high concentration. The aim o f the present study was therefore to investigate the ability of a wate r soluble extract of Hp to induce NO synthase in duodenal mucosa and e pithelial cells following its administration in vivo in rats and deter mine its association with cell damage. 3 Administration of Hp water ex tract (4 ml kg(-1)) led to the expression of the calcium-independent i nducible nitric oxide synthase (iNOS) after 4 h in the duodenum, deter mined as [C-14]-arginine conversion to citrulline. 4 This iNOS activit y was not reduced by pretreatment with anti-neutrophil serum (0.4 mi k g(-1), i.p., 3 h before challenge). However, dexamethasone pretreatmen t (1 mg kg(-1), i.v., 2 h before the extract), or administration of th e NO synthase inhibitor N-G-nitro-L-arginine methyl ester (L-NAME, 5 m g kg(-1), i.v., 2.5 h after the extract) reduced this activity. 5 Furt hermore, iNOS was expressed in duodenal isolated epithelial cells 4 h after the i.v. challenge with the extract, at a time when the cellular viability was also reduced, as assessed by trypan blue exclusion. 6 D examethasone pretreatment, administration of L-NAME, or pretreatment w ith polymyxin B (1 mg kg(-1), i.v.) which binds endotoxin, reduced bot h the iNOS activity and epithelial cell damage. 7 The induction of NO synthase by the Hp extract thus results in duodenal epithelial cell in jury and such actions could play a role in pathogenesis of peptic ulce r disease.