Eradication of Helicobacter pylori induces apoptosis and inhibits proliferation of heterotopic proliferative glands in infected Mongolian gerbils.
Mongolian gerbils infected with Helicobacter pylori (H. pylori ) develop heterotopic proliferative glands (HPGs) in the glandular stomach submucosa. To investigate the effects of H. pylori eradication on cell turnover in HPGs, three antibiotics, lansoprazole, amoxicillin and clarithromycin, were administered at 50 or 75 weeks after inoculation of H. pylori, and the stomachs were excised for histological examination at 1, 2, 4, 8 or 25 weeks thereafter. The HPGs were classified into gastric type (G-type) and others (GI + I-type), which included both pure intestinal (I-type) and gastric-and-intestinal mixed type (GI-type). Apoptosis and cell proliferation were evaluated by means of TUNEL assay and BrdU labeling, respectively. At 8 weeks post-eradication, apoptotic indices were significantly increased in the eradication group (G-type: 2.5%; GI + I-type: 7.2%) compared to the non-eradication group (G-type: 0.6%; GI + I-type: 2.1%: P < 0.01), while BrdU labeling indices were significantly decreased (G-type: 1.9%; GI + I-type: 6.8% as compared with 4.3% and 13.2%, respectively, P < 0.01 for both). At 25 weeks, the apoptotic indices were similarly higher [G-type: 0.4 (eradication group) vs. 0.2% (non-eradication group); GI + I-type: 5.8 vs. 1.1%, both P < 0.01], and the BrdU labeling indices (G-type: 0.8 vs. 2.2%, P < 0.01; GI + I-type: 5.1 vs. 11%, P < 0.05) continued to be lower in HPGs. Furthermore, there were highly significant reductions in the areas of HPGs at 8 and 25 weeks post-eradication. These findings demonstrated that eradication results in apoptosis and reduction of proliferation of HPGs in H. pylori-infected gerbils, these lesions thus being apparently reversible through regulation of cell kinetics.
Cao
Xueyuan
X
Division of Oncological Pathology, Aichi Cancer Center Research Institute, Aichi 464-8681.
Tsukamoto
Tetsuya
T
Nozaki
Koji
K
Shimizu
Nobuyuki
N
Mizoshita
Tsutomu
T
Kumagai
Toshiko
T
Kaminishi
Michio
M
Tatematsu
Masae
M
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000658:Amoxicillin / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017209:Apoptosis; D049109:Cell Proliferation; D002828:Choristoma / Q000188:drug therapy*; D017291:Clarithromycin / Q000627:therapeutic use; D005753:Gastric Mucosa; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000188:drug therapy / Q000473:pathology*; D016480:Helicobacter pylori; D007422:Intestines; D064747:Lansoprazole; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013270:Stomach
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000900:Anti-Bacterial Agents; D064747:Lansoprazole; D000658:Amoxicillin; D017291:Clarithromycin; D009853:Omeprazole