Eradication of Helicobacter pylori induces apoptosis and inhibits proliferation of heterotopic proliferative glands in infected Mongolian gerbils

Abstract

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. elicobacter pylori (H. pylori) infection has been implicated as a major cause of chronic gastritis and a strong risk factor for gastric adenocarcinoma. Epidemiological and experimental studies have demonstrated associations between H. pylori infection and the development of chronic superficial gastritis, atrophic gastritis and intestinal metaplasia.

Effect of Helicobacter pylori eradication on gastric carcinogenesis

“…17 Cao et al 23 reported that antimicrobial therapy induces apoptosis and inhibits proliferation in H. pylori-infected gerbil gastric mucosa. However, the effect of H. pylori eradication on pre-malignant (eg, dysplasia) and malignant histological lesions was not examined.…”

“…21 This regimen was selected based on previous studies demonstrating the efficacy of this therapy for H. pylori eradication in infected gerbils. 22,23 Sham therapy consisted of 500 ml sterile water delivered daily for 14 days. Infected and uninfected gerbils, treated with antibiotics or water, were euthanized 8 weeks post-treatment (Figure 1).…”

Late reactivation of sonic hedgehog by Helicobacter pylori results in population of gastric epithelial cells that are resistant to apoptosis: Implication for gastric carcinogenesis

“…However, most in vitro studies have shown the opposite result, that is, apoptosis prevails rather than proliferation after H. pylori or its supernatants treatment. Therefore, it is suggested that increased cell proliferation in gastric epithelium in vivo might be an indirect or secondary response to H. pylori infection [43][44][45]. Together with the previous publications that suppressed apoptosis might be one of major pathogenic factors in H. pylori-associated carcinogenesis [46][47][48] and oncogenic stem cells contributed to H. pylori-associated carcinogenesis [49], we could conclude that the reemergence of Shh expressing cells can explain these compensatory or counteractive privileges of proliferation through imbalanced epithelial turnover and this anti-apoptotic steps and proliferative privileges through Shh reactivation could be the necessary path for H. pylori-associated carcinogenesis.…”

Helicobacter pylori infection stimulates intestinalization of endocrine cells in glandular stomach of Mongolian gerbils

“…Samples (0.8 mL) containing approximately 1.0 × 10 8 colonyforming units per mL were used as the inoculum, as described earlier. (16)(17)(18)(19) Uninfected gerbils underwent sham inoculation using the same sterile Brucella broth.…”

“…Samples (0.8 mL) containing approximately 1.0 × 10 8 colonyforming units per mL were used as the inoculum, as described earlier. (16)(17)(18)(19) Uninfected gerbils underwent sham inoculation using the same sterile Brucella broth.The animals were divided into two major groups: H. pyloriinfected (Hp[+]), and non-infected (Hp [-]) groups, and each group was subclassified with reference to time of death at 50, 75 and 100 weeks. Finally, the animals (n = 70) were divided into Hp(+)-50-week (n = 18), Hp(+)-75-week (n = 6), Hp(+)-100-week (n = 17), Hp(-)-50-week (n = 19), Hp(-)-75-week (n = 6) and Hp(-)-100-week (n = 4) groups (Fig.…”