Reactive Nitrogen Species Mediate DNA Damage in Helicobacter pylori-Infected Gastric Mucosa

被引:38
作者
Katsurahara, Masaki [1 ]
Kobayashi, Yoshinao [1 ]
Iwasa, Motoh [1 ]
Ma, Ning [2 ]
Inoue, Hiroyuki [1 ]
Fujita, Naoki [1 ]
Tanaka, Kyosuke [1 ]
Horiki, Noriyuki [1 ]
Gabazza, Esteban C. [1 ]
Takei, Yoshiyuki [1 ]
机构
[1] Mie Univ, Grad Sch Med, Div Clin Med & Biochem Sci, Dept Gastroenterol & Hepatol, Tsu, Mie 5148507, Japan
[2] Suzuka Univ Med Sci, Fac Hlth Sci, Tsu, Mie, Japan
关键词
Helicobacter pylori; oxidative stress; nitrative stress; reactive nitrogen species; 8-nitroguanine; chronic gastritis; eradication; NITRIC-OXIDE SYNTHASE; OXIDATIVE STRESS; CAGA PROTEIN; IN-VIVO; CANCER; CARCINOGENESIS; ERADICATION; ACCUMULATION; INFLAMMATION; EXPRESSION;
D O I
10.1111/j.1523-5378.2009.00719.x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) can play an important role in cellular injury and carcinogenesis of gastric epithelial cells infected with Helicobacter pylori. 8-OH-deoxy guanosine (8-OHdG) and 8-nitroguanine (8-NG) are markers for ROS- and RNS-mediated DNA oxidation, respectively. in this study, RNS-mediated DNA damage in gastric mucosa was observed directly using a newly developed antibody to 8-NG to clarify how H. pylori infection causes nitrative DNA damage to gastric epithelial cells. Methods: Immunohistochemistry with anti-8-OHdG and anti-8-NG antibodies was performed on gastric tissue samples from 45 patients (25 men and 20 women) with H. pylori-positive gastritis and 19 patients (11 men and 8 women) exhibiting Successful H. pylori eradication. Histologic factors for gastric mucosal inflammation were graded according to the guidelines of the Updated Sydney system. Results: In corpus mucosa, 8-OHdG and 8-NG production were significantly associated with the degree of glandular atrophy, infiltration of chronic inflammatory cells and intestinal metaplasia in the glandular epithelial cells. Successful H. pylori eradication resulted in a significant reduction of chronic inflammatory cell infiltration and neutrophilic activity. Mean 8-OHdG production was lower after H. pylori eradication in both corpus and antral mucosa (p = .022 and .049, respectively). However, the reduction in 8-NG exhibited was more pronounced than the reduction of 8-OhdG (p = .004 and .007, respectively). Conclusions: Helicobacter pylori infection can induce inflammatory cells infiltration, which evokes DNA damage of gastric epithelial cells through ROS and RNS production. 8-NG might be a more sensitive biomarker than 8-OHdG for H. pylori-induced DNA damage in gastric mucosa.
引用
收藏
页码:552 / 558
页数:7
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