Helicobacter pylori-associated gastric pro- and antioxidant formation in Mongolian gerbils

Helicobacter pylori colonized gastric mucosa is manifest in a significant neutrophil infiltration with an extensive level of oxyradical formation. Mongolian gerbil is one of the excellent models for H. pylori-infection. The present study was designed to investigate pro- and antioxidant formation in the stomach of H. pylori-positive gerbils. Fourteen male Mongolian gerbils (MGS/Sea) were orally inoculated with H. pylori (ATCC43504) (Hp group) and 15 gerbils were inoculated with the culture media (Control). H. pylori infection was confirmed by the serum anti-H. pylori IgG test. Each gerbil was evaluated 6 or 12 weeks after the inoculation. Neutrophil infiltration was assessed by the tissue MPO activity. Mucosal oxidative stress was evaluated by thiobarbituric acid-reactive substances (TBARS), total glutathione contents, glutathione peroxidase (GSHPx) activity and Cu-, Zn-superoxide dismutase (SOD) activity. In Hp group, the H. pylori was persistently infected until 12 weeks. The level of MPO activity was significantly higher in Hp group at 6 and 12 weeks. Although the levels of TBARS and total glutathione were within the same range as controls at 6 weeks, they were significantly increased at 12 weeks. However, GSHPx activity was significantly increased at 6 weeks, but became the same range with the controls at 12 weeks. SOD activity showed no significant increase in Hp group at 6 and 12 weeks. In conclusion, H. pylori inoculation induced gastric mucosal neutrophil activation and pro-oxidant formation and also increased total glutathione contents, one of the mucosal antioxidants in gerbils.     

Effect of probiotics and triple eradication therapy on the cyclooxygenase (COX)-2 expression, apoptosis, and functional gastric mucosal impairment in Helicobacter pylori-infected Mongolian gerbils

BACKGROUND: Helicobacter pylori infection in Mongolian gerbils is an established experimental model of gastric carcinogenesis that mimics H. pylori-positive patients developing gastric ulcer and gastric cancer, but the effect of probiotic therapy on functional aspects of this infection remains unknown. METHODS: We compared the effects of intragastric inoculation of gerbils with H. pylori strain (cagA+ vacA+, 5 x 10(6) colony forming units/ml) with or without triple therapy including omeprazole, amoxicillin, and tinidazol or probiotic bacteria Lacidofil. Histology of glandular mucosa, the viable H. pylori, and density of H. pylori colonization were evaluated. The gastric blood flow was measured by H2-gas clearance method; the plasma gastrin and gastric luminal somatostatin were determined by RIA and expression of cyclooxygenase (COX)-2 and apoptotic Bax and Bcl-2 proteins were evaluated by Western blot. RESULTS: The gastric H. pylori infection was detected in all animals by histology and H. pylori culture. Basal gastric acid was significantly reduced in H. pylori-infected animals but not in those with triple therapy or Lacidofil. Early lesions were seen already 4 weeks upon H. pylori inoculation and consisted of chronic gastritis and glandular atypia associated with typical regenerative hyperplasia and increased mitotic activity and formation of apoptotic bodies. The H. pylori infection was accompanied by the fall in gastric blood flow, the marked increase in plasma gastrin, the significant fall in gastric somatostatin levels and Bcl-2 protein expression, and the rise in expression of COX-2 and Bax proteins. These mucosal changes were counteracted by the triple therapy and Lacidofil. CONCLUSIONS: H. pylori infection in gerbils, associated with regenerative hyperplasia of glandular structure, results in the suppression of gastric secretion, overexpression of COX-2, and enhancement in apoptosis and impairment of both, gastric blood flow and gastrin-somatostatin link that were reversed by anti-H. pylori triple therapy and attenuated by probiotics.     

Influence of vitamin E on gastric mucosal injury induced by Helicobacter pylori infection

We investigated the effect of vitamin E on gastric mucosal injury induced by Helicobacter pylori (H. pylori) infection. Male Mongolian gerbils were divided into 4 groups (normal group without H. pylori infection, vitamin E-deficient, -sufficient and -supplemented groups with H. pylori infection). Following oral inoculation with H. pylori (ATCC43504 2 x 10(8) CFU), animals were fed diets alpha-tocopherol 2 mg/100 g diet in the normal and vitamin E-sufficient groups and alpha-tocopherol 0.1 mg/100 g and 50 mg/100 g in the vitamin E-deficient and -supplemented groups, respectively, for 24 weeks. Chronic gastritis was detected in all gerbils inoculated H. pylori. Gastric ulcer was detected in 2 of 7 gerbils only in the vitamin E-deficient group. In the vitamin E-deficient group, myeloperoxidase activity and mouse keratinocyte derived chemokine (KC) in gastric mucosa was significantly higher than in the vitamin E supplemented group. Subsequently, in an in vitro study expression of CD11b/CD18 on neutrophils was enhanced by H. pylori water extract. This effect was suppressed in a dose dependent manner by the addition of alpha-tocopherol. These results suggest that vitamin E has a protective effect on gastric mucosal injury induced by H. pylori infection in gerbils, through the inhibition of accumulation of activated neutrophils.     

The role of luminal factors in the recovery of gastric function and behavioral changes after chronic Helicobacter pylori infection

The role of chronic infections, such as Helicobacter pylori (Hp), to produce sustained changes in host physiology remains controversial. In this study, we investigate whether the antigenic or bacterial content of the gut, after Hp eradication, influences the changes in gut function induced by chronic Hp infection. Mice were infected with Hp for 4 mo and then treated with antibiotics or placebo for 2 wk. Gastric emptying was measured using videofluoroscopy, feeding behavior using a 24-h feeding system, and intestinal permeability using an isolated jejunal segment arterially perfused with an artificial oxygen carrier, hemoglobin vesicles. Immune responses were assessed by CD3(+) cell counts and anti-Hp antibodies using ELISA. To determine the role of luminal factors in host physiology posteradication, groups of mice received the probiotics containing Lactobacillus rhamnosus R0011 and L. helveticus R0052 or placebo for 2 wk or crude Hp antigen weekly for 2 mo. Chronic Hp infection was associated with delayed gastric emptying, increased intestinal permeability, and increased gastric CD3(+) cell counts. Hp-induced altered feeding patterns did not reverse after eradication. Probiotics accelerated the recovery of paracellular permeability and delayed gastric emptying, improved the CD3(+) cell counts, and normalized altered feeding patterns posteradication. Hp antigen resulted in increased anti-Hp antibodies and increased CD3(+) cell counts in the stomach and delayed recovery of gastric function. Our results suggest that the bacterial content of the gut, as well as the presence of relevant antigens, influences the rate of recovery of host pathophysiology induced by chronic Hp infection. These changes do not seem to occur in association with modulation of intestinal permeability.     

Suppressed apoptosis in the inflamed gastric mucosa of Helicobacter pylori-colonized iNOS-knockout mice

Deregulated cell turnover in Helicobacter pylori (H. pylori)-colonized gastric mucosa has been suggested to be linked to the gastric carcinogenesis pathway. We previously reported attenuation of apoptosis and enhancement of cellular proliferation in the H. pylori-colonized gastric mucosa of Mongolian gerbils as compared to that in mice, which might reflect a specific link between H. pylori colonization and carcinogenesis in the Mongolian gerbils; the difference between the two strains could be attributable to differences in the host genetic background. Inducible-type nitric oxide synthase (iNOS) is thought to participate in not only the inflammatory response, but also in the regulation of gastric mucosal cell turnover in H. pylori-colonized gastric mucosa. Thus, the present study was designed to examine gastric leukocyte activation and epithelial cell apoptosis in the gastric mucosa following H. pylori inoculation in iNOS-knockout mice. Methods: iNOS-knockout mice (iNOS^−/−) and their iNOS^+/+ littermates were orally inoculated with the Sydney strain of H. pylori (SS1, 10⁸ colony-forming units [CFU]). H. pylori infection was confirmed by microaerobic bacterial culture. The stomach of each mouse was evaluated 14 weeks and 30 weeks after the inoculation. Gastric mucosal accumulation of polymorphonuclear leukocytes (PMN) was assessed by determining the myeloperoxidase (MPO) activity and histological score based on the updated Sydney system. The level of apoptosis was determined by estimation of the cytoplasmic levels of mono- and oligonucleosomes and by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method. Results: The SS1-inoculated mice showed persistent H. pylori colonization for 12 weeks. While gastric mucosal PMN infiltration increased following SS1 inoculation in both iNOS^+/+ and iNOS^−/−strains, enhanced DNA fragmentation was observed in only SS1-colonized iNOS^+/+ mice, and not in the iNOS^−/− mice. In conclusion, although the recruitment of PMN in response to H. pylori was evoked even in the gastric mucosa of iNOS^−/− mice, epithelial cell apoptosis induced by H. pylori was attenuated in this strain. These data suggest that iNOS may play an important role in promoting apoptosis in the H. pylori-infected inflamed gastric mucosa, and that persistent inflammation without apoptosis in iNOS^−/− mice with H. pylori infection may be linked to preneoplastic transformation.     

Gastric mucosal changes induced by long term infection with Helicobacter pylori in Mongolian gerbils: effects of bacteria eradication.

Helicobacter pylori infection has been reported to induce various mucosal changes, including gastric adenocarcinoma, in Mongolian gerbils 62 weeks after inoculation. Using Mongolian gerbils, this study examined whether or not eradication of the bacteria with drugs at specified times after infection prevents the development of mucosal changes. After orally inoculating with H. pylori (TN2GF4, vacA- and cagA-positive), the animals were killed 18 months later. Four or 8 months after H. pylori inoculation, eradication was performed by concurrent treatment with omeprazole+clarithromycin. Immediately after treatment ended, in both the 5 and 9 month groups, it was verified that H. pylori was completely eradicated. Autopsy performed 18 months after H. pylori inoculation revealed gastric hyperplastic polyps with erosive lesions and ulcers that were grossly visible in the non-treated control group. In addition, atrophic gastritis, intestinal metaplasia, carcinoids, and adenocarcinomas were histologically observed in the animals. In animals eradicated after 4 months and autopsied after 18 months, however, such mucosal changes were not observed. In contrast, intestinal metaplasia and mucosal atrophy was observed in animals eradicated after 8 months and autopsied after 18 months. It was concluded that early eradication of H. pylori infection with drug therapy can prevent severe gastric mucosal changes, to include adenocarcinomas, in Mongolian gerbils.     

Gastric mucosal changes induced by long term infection with Helicobacter pylori in Mongolian gerbils: effects of bacteria eradication

Helicobacter pylori infection has been reported to induce various mucosal changes, including gastric adenocarcinoma, in Mongolian gerbils 62 weeks after inoculation. Using Mongolian gerbils, this study examined whether or not eradication of the bacteria with drugs at specified times after infection prevents the development of mucosal changes. After orally inoculating with H. pylori (TN2GF4, vacA- and cagA-positive), the animals were killed 18 months later. Four or 8 months after H. pylori inoculation, eradication was performed by concurrent treatment with omeprazole+clarithromycin. Immediately after treatment ended, in both the 5 and 9 month groups, it was verified that H. pylori was completely eradicated. Autopsy performed 18 months after H. pylori inoculation revealed gastric hyperplastic polyps with erosive lesions and ulcers that were grossly visible in the non-treated control group. In addition, atrophic gastritis, intestinal metaplasia, carcinoids, and adenocarcinomas were histologically observed in the animals. In animals eradicated after 4 months and autopsied after 18 months, however, such mucosal changes were not observed. In contrast, intestinal metaplasia and mucosal atrophy was observed in animals eradicated after 8 months and autopsied after 18 months. It was concluded that early eradication of H. pylori infection with drug therapy can prevent severe gastric mucosal changes, to include adenocarcinomas, in Mongolian gerbils.     

Mast cells and cells producing alpha-endorphin in the mucosa of the antral section of the stomach

The distribution of mast cells, alpha-endorphine-producing cells (AER-cells) and argyrophilic cells in lamina propria of the antral mucosa was determined quantitatively in 13 normal men. The cells were detected by histochemical and immunohistochemical (PAP) methods. The form and site of AER-cells resembled those of mast cells and mucosal argyrophilic cells (in lamina propria). The authors assume that part of human gastric mucosal cells have argyrophilic properties and contain alpha-endorphine.     

Long-standing gastric mucosal barrier dysfunction in Helicobacter pylori-induced gastritis in mongolian gerbils

BACKGROUND AND AIMS: Helicobacter pylori infection causes chronic gastritis and leads to peptic ulcer and gastric adenocarcinoma. An impaired gastric mucosal barrier could be involved in these processes. Our aim was to investigate gastric barrier function in H. pylori-induced gastritis. METHODS: Stripped gastric mucosal tissues of H. pylori-infected Mongolian gerbils (4 weeks and 70 weeks after inoculation, respectively) and controls were mounted in Ussing chambers. (51)Cr-EDTA (paracellular probe) and horseradish peroxidase (HRP, protein antigen) were used to assess mucosal barrier function. The electrophysiological parameters of the mucosa (transepithelial potential, short circuit current, and transepithelial resistance) were monitored as measurements of barrier integrity and viability. Tissue histology was performed to assess inflammation. RESULTS: In the antrum, both short-term gastritis [4.68 (3.88-5.74) x 10(-6) vs. control 2.86 (2.34-3.77) x 10(-6) cm/s, p <.001] and gastritis of long-standing [5.72 (3.88-10.94) x 10(-6) cm/s, p <.001 vs. control] showed increased permeability to (51)Cr-EDTA. In long-standing antral gastritis there was also an increased HRP flux [9.01 (2.98-45.02) vs. control 0.52 (0.06-1.20) pmol/h/cm(2), p <.001]. In the corpus, permeability to (51)Cr-EDTA was increased only in long-standing gastritis [4.63 (3.64-7.45) x 10(-6) vs. control 2.86 (2.12-3.98) x 10(-6) cm/s, p <.01]. Gastric mucosal permeability to (51)Cr-EDTA was correlated to histological inflammation and inflammatory activity. The levels of serum anti-H. pylori immunoglobulin G were positively correlated to HRP flux and (51)Cr-EDTA permeation. CONCLUSIONS: Helicobacter pylori-induced gastritis in Mongolian gerbils was associated with a long-standing gastric mucosal barrier dysfunction. The barrier defect extended from the antrum into the corpus over time. This impaired barrier function may contribute to perpetuation of chronic inflammation and may be involved in H. pylori-associated carcinogenesis.     

Enterocromaffin-like cell tumor induced by Helicobacter pylori infection in Mongolian gerbils

Background. Gastric carcinoids are strongly associated with chronic atrophic gastritis A, and it is suggested that hypergastrinemia plays a critical role in development of gastric carcinoids. Since Helicobacter pylori infection causes hypergastrinemia, it is held that H. pylori infection produces gastric carcinoids. We followed the histological changes of H. pylori‐infected stomachs of Mongolian gerbils for a long time. Materials and Methods. Five‐week‐old‐male Mongolian gerbils were infected with H. pylori ATCC 43504 with cagA gene, expressing vacuolating cytotoxin. Determination of the serum gastrin and histopathological examination of the stomach at 6, 12, 18, and 24 months after H. pylori inoculation was studied and compared with uninfected animals . Results In infected animals, the gastric carcinomas appeared 18 and 24 months after infection. Endocrine cell dysplasias and carcinoids with marked atrophic gastritis of the oxyntic mucosa were observed in the infected animals 24 months after H. pylori inoculation. The serum gastrin level in the infected group increased from an average of 86.2 pg/ml at the beginning of the study to an average of 498 pg/ml and 989 pg/ml at 18 and 24 months after infection, respectively. These changes in the serum gastrin levels were significant compared with uninfected controls that showed no changes. Conclusions. H. pylori infection caused not only gastric carcinomas but also enterochromaffin‐like cell tumors in Mongolian gerbils, due to hypergastrinemia. This model is thought to be useful to study the relationship between hypergastrinemia and gastric carcinoids.     

Enterohepatitis in Mongolian gerbils (Meriones unguiculatus) inoculated perorally with Tyzzer's organism (Bacillus piliformis)

Enterohepatitis was produced in Mongolian gerbils by intragastric inoculation with Tyzzer's organism from natural infection of a gerbil. Death occurred in 50 to 60% animals 5 to 7 days postinoculation (p.i.). On day 3 p.i., when a few necrotic foci appeared in the liver, a large amount of bacterial antigen was present within ileocecal enterocytes and reticuloendothelial cells of the Peyer's patches. Neutrophil and monocyte infiltration was found in the lamina propria. On day 5 or 6 p.i. there was severe necrotizing and hemorrhagic ileotyphlocolitis. Bacterial antigen was abundant within not only enterocytes, but also smooth muscle cells of the ileum and jejunum as well as reticular cells of the mesenteric lymph nodes. On day 7 p.i. the intestinal lesions subsided in the presence of fewer bacteria, while necrotizing hepatitis became well developed. The results indicated that Mongolian gerbils were highly susceptible to the oral route of infection with the Tyzzer's organism.     

Effect of dietary anti-urease immunoglobulin Y on Helicobacter pylori infection in Mongolian gerbils

BACKGROUND AND AIM: Helicobacter pylori is known to be a major pathogenic factor in the development of gastritis, peptic ulcer disease and gastric cancer. Recently, chicken egg yolk immunoglobulin Y (IgY) has been recognized as an inexpensive antibody source for passive immunization against gastrointestinal infections. The present study was designed to investigate the effect of anti-urease IgY on H. pylori infection in Mongolian gerbils. METHODS: H. pylori-infected Mongolian gerbils were administered a diet containing anti-urease IgY, with or without famotidine (F). After 10 weeks, bacterial culture and measurement of the gastric mucosal myeloperoxidase (MPO) activity were performed. In a second experiment, another group of gerbils was started on a diet containing F + IgY a week prior to H. pylori inoculation. After 9 weeks, these animals were examined. RESULTS: In the H. pylori-infected gerbils, there were no significant differences in the level of H. pylori colonization among the different dietary and control groups. However, the MPO activity was significantly decreased in the H. pylori group administered the F + IgY diet compared with that in the H. pylori group administered the IgY, F, or control diet. Furthermore, in the gerbils administered the F + IgY diet prior to the bacterial inoculation, inhibition of H. pylori colonization and suppression of the elevated gastric mucosal MPO activity were observed. CONCLUSIONS: Oral administration of urease-specific IgY not only inhibited H. pylori disease activity in H. pylori-infected gerbils, but also prevented H. pylori colonization in those not yet infected. These encouraging results may pave the way for a novel therapeutic and prophylactic approach in the management of H. pylori-associated gastroduodenal disease.     

Effects of antioxidant vitamin supplements on Helicobacter pylori-induced gastritis in Mongolian gerbils

BACKGROUND: Epidemiological studies show that high intake of food-bound vitamin C and E reduces the risk of gastric cancer. Whether dietary supplementation with antioxidant micronutrients interferes with Helicobacter pylori infection and associated diseases is unclear. The aim of this study was to investigate if dietary vitamin C or E supplementation influences the progression of gastritis, gastric mucosal nitrosative and oxidative protein damage, gastric mucosal lipid peroxidation, or gastric mucosal oxidative DNA damage in H. pylori-infected Mongolian gerbils. MATERIALS AND METHODS: Gerbils were divided into four groups: H. pylori-infected animals fed with vitamin C- or vitamin E-supplemented food, and infected and uninfected animals given standard rodent food. Subgroups of animals were killed at different time-points until 52 weeks postinfection. Concentrations of 3-nitrotyrosine and thiobarbituric acid-reactive substances (TBARS) in the gastric mucosa were determined with an immunodot blot and a fluorometric method, respectively. Mucosal concentrations of carbonyl carbons on proteins and 8-hydroxydeoxyguanosine were determined by enzyme-linked immunosorbent assay. Gastritis was scored semiquantitatively. RESULTS: Vitamin supplements had no effect on the colonization with H. pylori. Vitamin C as well as vitamin E supplements reduced mucosal 3-nitrotyrosine concentrations to normal levels in infected animals. Vitamin E supplements decreased mucosal protein carbonyls and TBARS in short-term gastritis. In addition, vitamin C supplements caused attenuated mucosal oxidative DNA damage and milder mucosal inflammation in short-term gastritis. CONCLUSION: Vitamin C or vitamin E supplementation leads to some short-term protective effects on H. pylori-induced gastritis in Mongolian gerbils. These effects seem to subside over time when the infection persists.     

Scanning electron microscopy of vascular architecture in the gastric mucosa of the golden hamster

Summary The three-dimensional architectures and the regional differences of the vascular system in the mucosa of the hamster stomach were revealed by scanning electron microscopy of corrosion casts. In the forestomach, the vascular network spreads two-dimensionally in a thin lamina propria. In the corpus and the antrum, the capillaries in the thick lamina propria are well developed, extending three-dimensionally along the gastric pits and glands. In the corpus, the submucosal arteries enter the lamina propria to become ascending capillaries, which project toward the top of the lamina propria and anastomose to create a capillary network beneath the mucosal epithelium. A subepithelial capillary is much wider in diameter than an ascending capillary and is, therefore, a sinusoid capillary. Subepithelial capillaries join descending venules, which are less numerous than the ascending capillaries. Near the gastric lumen, the capillaries in the corpus can be classified into two types: arched type in the cephalic (upper) region and honeycomb type in the caudal (lower) region. In the antrum, the submucosal arterial plexus is less well developed than that in the corpus. The mucosal aspect of the corrosion cast shows many clumps, formed by a unit of capillary network. Functional significances of different vascular architectures in the gastric mucosa of the forestomach, corpus, and antrum are discussed.This study was supported in part by grants from the Research Fund of the Ministry of Education, Science, and Culture, Japan     

Characteristics of a clinical isolate of urease-negative Helicobacter pylori and its ability to induce gastric ulcers in Mongolian gerbils

BACKGROUND: We clinically obtained urease-negative mutant strains of Helicobacter pylori. The goal of this study was to investigate the ability of the urease-negative strain to colonize and subsequently damage the gastric mucosa in Mongolian gerbils. In addition, the genes encoding the urease production in the test strain were analyzed, and other genes encoding the virulence factors, cytotoxin-associated protein and vacuolating-cytotoxin were evaluated. MATERIALS AND METHODS: The character of urease-negative isolates of H. pylori was defined. The identification of H. pylori was confirmed by polymerase chain reaction (PCR). The H. pylori isolate was transfected into Mongolian gerbils as previously described, which were followed up to 42 weeks, and the changes in their gastric mucosa were examined histologically. RESULTS AND CONCLUSION: Fifteen Mongolian gerbils orally infected with 10(7) colony forming units of urease-negative H. pylori were killed at 4, 12, 24, 36 and 42 weeks (n = 3) after infection. Culture medium without urease-negative H. pylori was given to the Mongolian gerbils as control. H. pylori continued to exist in the subject's stomach and gastric ulceration was observed and compared with the control. Clinically obtained urease-negative H. pylori continued to exist for at least 42 weeks in the subject's stomach and it induced gastric ulcers. These data demonstrated that the urease in H. pylori was not a necessary factor in the formation of gastric ulcers in the Mongolian gerbil model.     

尾斑瘰螈主要消化器官组织结构观察

本研究采用组织学方法对尾斑瘰螈(Paramesotriton caudopunctatus)的消化器官进行了显微结构观察。结果表明,尾斑瘰螈食管较短,胃、肠壁组织结构分为黏膜层、黏膜下层、肌层和外膜,小肠前段的黏膜下层缺失。胃黏膜层中有许多胃腺,胃腺细胞胞质含嗜酸性颗粒。小肠前段绒毛细长密集,中段、后段逐渐短小稀疏,在黏膜层的固有膜中没有肠腺分布。肝实质中肝小叶界限不明显,肝小叶内有大量色素颗粒成团分布。     

Apoptosis in gastric mucosa with stress-induced gastric ulcers.

The maintenance of gastric mucosal integrity depends upon the interplay between epithelial cell proliferation and apoptosis (programmed cell death). The Bcl-2 family of proteins plays a central role in the regulation of apoptotic cell death by suppressing the apoptosis while some others such as Bax proteins promote this process. Stress-induced gastric ulcerations are accompanied by the fall in gastric mucosal cell proliferation but little is known about the influence of the stress on the apoptosis in gastric mucosa. In the present study, the gastric epithelial apoptosis was determined by means of expression of Bax and Bcl-2 mRNA in the gastric mucosa following acute stress. Wistar rats were exposed to mild water immersion and restraint stress (WRS) for 3.5 h and then sacrificed at 0, 2, 4, 6, 12 and 24 h after the termination of WRS. At each time interval after WRS, the gastric blood flow (GBF) and the proliferating cell nuclear antigen (PCNA) labeling were determined. The apoptosis rate in the gastric mucosa was determined by the terminal deoxynucleotidyl transferase (TDT) mediated 2-deoxyuridine 5-triphosphate (dUTP)-biotin nick end-labeling (TUNEL) staining method and the expression of Bax and Bcl-2 mRNA was analyzed by RT-PCR and southern blot hybridization. WRS produced multiple erosions accompanied by the fall in GBF and PCNA index and by a dramatic enhancement in gastric epithelial apoptosis rate reaching maximum at 4 h after exposure to WRS. Following 6 and 12 h after the end of WRS the apoptotis declined but even 24 h after WRS it failed to reach the value recorded in intact gastric mucosa. The PCNA index was still significantly inhibited at 2 h after WRS but then showed significant rise at 6 and 12 h to reach at 24 h after WRS, the level similar to that measured in intact gastric mucosa. The expression of Bax mRNA was detected in intact gastric mucosa and gradually increased in first 4 h after WRS to decline at 24 h to the level not significantly different from that observed in the intact mucosa. In contrast, the expression of Bcl-2 mRNA was almost undetectable during first 4 h but showed strong signal at 6 and 12 h to decline to the control level 24 h after WRS. We conclude that: 1. Healing of WRS lesions involves an increase in GBF and mucosal cell proliferation and 2. The enhancement in gastric epithelial apoptosis accompanies the mucosal damage induced by stress and this appears to be triggered by the shift from the cell death effector Bax to the cell death repressor Bcl-2 protein.     

Is Mongolian gerbil really adequate host animal for study of Helicobacter pylori infection-induced gastritis and cancer?

BACKGROUND: Many researches have been published to understand the pathogenesis and mechanism of Helicobacter pylori (Hp)-associated diseases, including gastritis followed by gastric cancer, using Mongolian gerbil (MG) model because Hp could be hardly inoculated in other animal species. The aim of this study was to evaluate the induction ability of heat shock protein (HSP70) and protective ability in the gastric mucosa of MG comparing with those of Sprague-Dawley (SD) rats, since HSP70 is a key molecule known to be involved in important biological activities such as apoptosis, carcinogenesis, and cytoprotection from cytotoxic damage. MATERIALS AND METHODS: Basal expression level and induction ability of gastric mucosal HSP70 were evaluated by immunoblotting and densitometric analysis in MG and SD rats before and after HSP-induction by zinc l-carnosine, gastric HSP70 inducer, administration. Mucosal protective ability against water-immersion stress-induced mucosal lesion was also compared. RESULTS: Basal expression level of HSP70 was not significantly different between MG and SD rats. However, HSP70-induction by zinc derivatives was not observed in MG. Mucosal lesion induced by water-immersion stress was significantly severe in MG compared with SD rats. CONCLUSIONS: MG might be special (not ordinary) animal, in which HSP70-induction was absent and has extremely poor mucosal protective ability in view of HSP-dependent cytoprotection in the gastric mucosa. Our results may suggest that MG is not an adequate animal to evaluate the effect of Hp-infection-associated gastric inflammation followed by development of gastric cancer.