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
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.