OBJECTIVE: To elucidate the molecular mechanisms underlying sepsis-induced injury in mouse intestinal organoids and investigate the possible mechanisms or potential drug targets of myeloid differentiation factor 88 inhibitor [TJ-M2010-5 (TJ5)] on this condition. METHODS: Small intestinal organoids from C57BL/6 mice aged 6-8 weeks were established and characterized using immunofluorescence for cell growth and proliferation marker nuclear antigen Ki-67, goblet cell marker mucin-2 (MUC-2), epithelial cell marker E-cadherin, and Paneth cell marker lysozyme (Lyz). Small intestinal organoids after 3 days of passaging were divided into different groups: a normal control group treated with culture medium containing 0.2% dimethyl sulfoxide (DMSO) for 10 hours, a lipopolysaccharide (LPS) group treated with culture medium containing 200 mg/L LPS and 0.2% DMSO for 10 hours, and a TJ5 group pre-treated with 10 mmol/L TJ5 for 2 hours followed by treatment with culture medium containing 200 mg/L LPS for 10 hours. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to measure the expression levels of interleukin-6 (IL-6) and zonula occludens-1 (ZO-1) in the small intestinal organoids. RNA transcriptome sequencing was performed on the small intestinal organoids from each group to analyze differentially expressed genes between groups, and significant enrichment was analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). RESULTS: By the 7th day of primary culture, mature organoids had formed, and their growth rate increased after passaging. Immunofluorescence identification showed expressions of Ki-67, MUC-2, E-cadherin, and Lyz, indicating that the mouse small intestinal organoids maintained their cellular composition and functional characteristics under in vitro culture conditions. RT-qPCR results showed that compared with the normal control group, the mRNA expression of IL-6 in the small intestinal organoids of the LPS group was significantly increased (2^-ΔΔCT: 1.83±0.16 vs. 1.02±0.28, P < 0.05), while the mRNA expression of ZO-1 was significantly decreased (2^-ΔΔCT: 0.53±0.11 vs. 1.01±0.18, P < 0.05). In contrast, the mRNA expression trends of both IL-6 and ZO-1 were reversed in the TJ5 group, showing statistically significant differences as compared with the LPS group (2^-ΔΔCT: IL-6 mRNA was 1.24±0.01 vs. 1.83±0.16, ZO-1 mRNA was 1.97±0.29 vs. 0.53±0.11, both P < 0.05). RNA transcriptome sequencing showed 49 differentially expressed genes in the LPS group compared to the normal control group, with 42 upregulated and 7 downregulated. Compared to the LPS group, the TJ5 group showed 84 differentially expressed genes, with 47 upregulated and 37 downregulated. GO enrichment analysis of these differentially expressed genes showed that the significantly enriched biological processes of the differentially expressed genes between the normal control group and the LPS group included responses to LPS, responses to molecule of bacterial origin and responses to bacterium. The significantly enriched biological processes of the differentially expressed genes between the LPS group and the TJ5 group included glutathione metabolic processes, responses to stress cellular and responses to chemical stimulus. In molecular function groups, glutathione binding and oligopeptide binding were significantly enriched by the differentially expressed genes. In cellular component classifications, the enrichment of the differentially expressed genes was mainly observed in the cytoplasm, endoplasmic reticulum, and microsomes. KEGG pathway enrichment analysis indicated that the differentially expressed genes between the normal control group and LPS group were enriched in IL-17 signaling pathways, tumor necrosis factor (TNF) signaling pathways, viral protein interactions with cytokines and cytokine receptors signaling pathways, and cytokine-cytokine receptor interaction signaling pathways. In contrast, the differentially expressed genes between the LPS and TJ5 groups were mainly enriched in atherosclerosis signaling pathways, ferroptosis signaling pathways, glutathione metabolism signaling pathways, and cytochrome P450-mediated drug metabolism signaling pathways. CONCLUSIONS Mouse small intestinal organoids were successfully extracted and cultured. TJ5 may exert its protective effects by regulating gene expression and related signaling pathways (fluid shear stress and atherosclerosis, ferroptosis, glutathione metabolism, cytochrome P450 drug metabolism, etc.) in sepsis-injured mouse small intestinal organoids. These genes and signaling pathways may be key targets for treating sepsis-induced intestinal injury.
Animals ; Mice ; Sepsis/genetics* ; Organoids/drug effects* ; Mice, Inbred C57BL ; Intestine, Small/metabolism* ; Gene Expression Profiling ; Transcriptome ; Lipopolysaccharides

In order to establish a stable in vitro culture platform for chicken small intestine three-dimensional (3D) organoids, in this study, crypt cells were collected from the small intestine of 18-day-old embryos of AA broilers. On the basis of the L-WRN conditioned medium, we optimized the culture conditions of chicken small intestinal organoids by adjusting the proportions of nicotinamide, N-acetylcysteine, LY2157299, CHIR99021, Jagged-1, FGF, and other cytokines to select the medium suitable for the long-term stable growth of the organoids. The optimization results showed that the addition of 1.5 µmol/L CHIR99021 significantly improved the organoid formation efficiency and organoid diameter. When 0.5 µmol/L Jagged-1 was added, a small amount of bud-like tissue appeared in organoids. After the addition of 50 ng/mL FGF-2, the rate of organoid germination was significantly increased. The 1.5 µmol/L CHIR99021, 0.5 µmol/L Jagged-1, and 50 ng/mL FGF-2 added in the medium can cooperate with each other to improve the formation and speed up the proliferation and differentiation of organoids, while improving the stemness maintenance of cells. The morphology, cell types, and culture characteristics of chicken small intestinal organoids were studied by HE staining, transmission electron microscopy, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), indirect immunofluorescence, and immunohistochemistry. The results showed that the 3D organoids of the chicken small intestine cultured in vitro were morphologically consistent with the chicken intestinal tissue and contained differentiated epithelial cells. In summary, we successfully established an in vitro culture system for chicken small intestinal organoids, providing a new method for the subsequent research on chicken intestinal physiology, pathology, and host-pathogen interaction mechanism and the development of relevant drugs.
Animals ; Organoids/metabolism* ; Intestine, Small/drug effects* ; Chickens ; Cell Culture Techniques/methods* ; Culture Media ; Chick Embryo ; Tissue Culture Techniques/methods*

OBJECTIVETo examine whether sodium tanshinone II A sulfonate (STS), the main effective component of Salvia miltiorrhiza is effective in relieving the microcirculatory disturbance of small intestine by suppressing the production of reactive oxygen species (ROS) in rats with sepsis.

METHODSA rat model of sepsis was induced by cecal ligation and puncture (CLP). Rats (n =40) were randomly divided into 4 groups: sham-operated group (sham, n =10), sepsis group (CLP, n =10), STS treatment group (STS, n =10) and ROS scavenger dimethylthiourea (DMTU, n =10) group. Animals in the STS group were injected with STS (1 mg/kg) for 10 min through the right external jugular vein after the CLP operation, and animals in the CLP group were given the same volume of normal saline after the CLP operation. Animals in the DMTU group were intraperitoneally injected with 5 mL/kg of 20% DMTU 1 h before CLP. The histopathologic changes in the intestinal tissues and changes of mesenteric microcirculation were observed. The levels of ROS in intestinal tissues from each group were qualitatively evaluated using a fluorescent microscope. The expressions of apoptosis signal-regulating kinase (ASK1), phosphorylated ASK1 (phospho-ASK1), p38 mitogen-activated protein kinases (p38 MAPK), phosphorylated p38 MAPK (phospho-p38 MAPK) and tissue factor (TF) were determined by Western blotting.

RESULTSIt was shown that there were obvious microcirculatory disturbance (P <0.05) and tissue injuries in intestinal tissues after CLP operation. The levels of ROS production, phospho-ASK1, phospho-p38 MAPK and TF were increased. Both STS and DMTU suppressed ROS, phospho-ASK1, phospho-p38 MAPK and TF production, and ameliorated the microcirculatory disturbance and tissues injury (P <0.01).

CONCLUSIONSTS can ameliorate the microcirculatory disturbance of the small intestine by attenuating the production of ROS in rats with sepsis.

Animals ; Intestine, Small ; blood supply ; drug effects ; pathology ; MAP Kinase Kinase Kinase 5 ; metabolism ; Male ; Microcirculation ; drug effects ; Phenanthrenes ; chemistry ; pharmacology ; therapeutic use ; Phosphorylation ; drug effects ; Rats, Wistar ; Reactive Oxygen Species ; metabolism ; Sepsis ; drug therapy ; enzymology ; pathology ; physiopathology ; Thromboplastin ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

Vertical sleeve gastrectomy (VSG) is becoming more and more popular among the world. Despite its dramatic efficacy, however, the mechanism of VSG remains largely undetermined. This study aimed to test interferon (IFN)-γ secretion n of mesenteric lymph nodes in obese mice (ob/ob mice), a model of VSG, and its relationship with farnesoid X receptor (FXR) expression in the liver and small intestine, and to investigate the weight loss mechanism of VSG. The wild type (WT) mice and ob/ob mice were divided into four groups: A (WT+Sham), B (WT+VSG), C (ob/ob+Sham), and D (ob/ob+VSG). Body weight values were monitored. The IFN-γ expression in mesenteric lymph nodes of ob/ob mice pre- and post-operation was detected by flow cytometry (FCM). The FXR expression in the liver and small intestine was detected by Western blotting. The mouse AML-12 liver cells were stimulated with IFN-γ at different concentrations in vitro. The changes of FXR expression were also examined. The results showed that the body weight of ob/ob mice was significantly declined from (40.6±2.7) g to (27.5±3.8) g on the 30th day after VSG (P<0.05). At the same time, VSG induced a higher level secretion of IFN-γ in mesenteric lymph nodes of ob/ob mice than that pre-operation (P<0.05). The FXR expression levels in the liver and small intestine after VSG were respectively 0.97±0.07 and 0.84±0.07 fold of GAPDH, which were significantly higher than pre-operative levels of 0.50±0.06 and 0.48±0.06 respectively (P<0.05). After the stimulation of AML-12 liver cells in vitro by different concentrations of IFN-γ (0, 10, 25, 50, 100, and 200 ng/mL), the relative FXR expression levels were 0.22±0.04, 0.31±0.04, 0.39±0.05, 0.38±0.05, 0.56±0.06, and 0.35±0.05, respectively, suggesting IFN-γ could distinctly promote the FXR expression in a dose-dependent manner in comparison to those cells without IFN-γ stimulation (P<0.05). It was concluded that VSG induces a weight loss in ob/ob mice by increasing IFN-γ secretion of mesenteric lymph nodes, which then increases the FXR expression of the liver and small intestine.
Animals ; Body Weight ; Cell Line ; Gastrectomy ; methods ; Gene Expression ; Hepatocytes ; cytology ; drug effects ; metabolism ; Interferon-gamma ; biosynthesis ; pharmacology ; secretion ; Intestine, Small ; drug effects ; metabolism ; Liver ; drug effects ; metabolism ; Lymph Nodes ; drug effects ; metabolism ; Mesentery ; drug effects ; metabolism ; Mice ; Mice, Obese ; Obesity ; metabolism ; pathology ; surgery ; Receptors, Cytoplasmic and Nuclear ; agonists ; genetics ; metabolism ; Weight Loss

OBJECTIVETo observe the effects of astragalus polysaccharide (AP) on the intestinal mucosal morphology, level of secretory IgA (s-IgA) in intestinal mucus, and distribution of T lymphocyte subsets in Peyer's patch in rats with severe scald injury.

METHODSOne hundred and thirty SD rats were divided into sham injury group (SI, sham injured, n = 10), scald group (S, n = 30), low dosage group (LD, n = 30), moderate dosage group (MD, n = 30), and high dosage group (HD, n = 30) according to the random number table. Rats in the latter 4 groups were inflicted with 30% TBSA full-thickness scald on the back. From post injury hour 2, rats in groups LD, MD, and HD were intraperitoneally injected with 0.5 mL AP solution with the dosage of 100, 200, and 300 mg/kg each day respectively, and rats in group S were injected with 0.5 mL normal saline instead. Ten rats from group SI immediately after injury and 10 rats from each of the latter 4 groups on post injury day (PID) 3, 7, 14 were sacrificed, and their intestines were harvested. The morphology of ileal mucosa was examined after HE staining; the level of s-IgA in ileal mucus was determined with double-antibody sandwich ELISA method; the proportions of CD3⁺, CD4⁺, CD8⁺ T lymphocytes in Peyer's patches of intestine were determined with flow cytometer, and the proportion of CD4⁺ to CD8⁺ was calculated. Data were processed with one-way analysis of variance, analysis of variance of factorial design, and SNK test.

RESULTS(1) Villi in normal form and intact villus epithelial cells were observed in rats of group SI immediately after injury, while edema of villi and necrosis and desquamation of an enormous amount of villi were observed in groups with scalded rats on PID 3, with significant infiltration of inflammatory cells. On PID 7, no obvious improvement in intestinal mucosal lesion was observed in groups with scalded rats. On PID 14, the pathology in intestinal mucosa of rats remained nearly the same in group S, and it was alleviated obviously in groups LD and MD, and the morphology of intestinal mucosa of rats in group HD was recovered to that of group SI. (2) On PID 3, 7, and 14, the level of s-IgA in intestinal mucus significantly decreased in groups S, LD, MD, and HD [(43 ± 5), (45 ± 5), (46 ± 5) µg/mL; (47 ± 5), (48 ± 5), (49 ± 6) µg/mL; (50 ± 6), (51 ± 5), (52 ± 5) µg/mL; (53 ± 6), (54 ± 5), (55 ± 5) µg/mL] as compared with that of rats in group SI immediately after injury [(69 ± 4) µg/mL, with P values below 0.05]. The level of s-IgA in intestinal mucus of rats in group MD was significantly higher than that in group S at each time point (with P values below 0.05), and that of group HD was significantly higher than that in groups S and LD at each time point (with P values below 0.05). (3) Compared with those of rats in group SI immediately after injury, the proportions of CD3⁺ T lymphocytes and CD4⁺ T lymphocytes significantly decreased in groups with scalded rats at each time point (with P values below 0.05), except for those in group HD on PID 14. The proportion of CD4⁺ T lymphocytes of rats in group LD was significantly higher than that in group S on PID 3 (P < 0.05). The proportions of CD3⁺ T lymphocytes and CD4⁺ T lymphocytes were significantly higher in groups MD and HD than in groups S and LD (except for the proportion of CD4⁺ T lymphocytes in group MD on PID 3 and 14) at each time point (with P values below 0.05). The proportion of CD3⁺ T lymphocytes on PID 7 and 14 and that of CD4⁺ T lymphocytes on PID 3 were significantly higher in group HD than in group MD (with P values below 0.05). Compared with that of rats in group SI immediately after injury, the proportion of CD8⁺ T lymphocytes significantly increased in the other 4 groups at each time point (with P values below 0.05). The proportion of CD8⁺ T lymphocytes was significantly lower in rats of group LD on PID 7 and 14 and groups MD and HD at each time point than in group S (with P values below 0.05). The proportion of CD8⁺ T lymphocytes was significantly lower in rats of group MD on PID 7 and 14 and group HD at each time point than in group LD (with P values below 0.05). The proportion of CD8⁺ T lymphocytes was significantly lower in rats of group HD on PID 7 and 14 than in group MD (with P values below 0.05). On PID 3, 7, and 14, the proportion of CD4⁺ to CD8⁺ was significantly lower in groups S, LD, MD, and HD (0.65 ± 0.11, 0.68 ± 0.13, 0.73 ± 0.22; 0.76 ± 0.15, 0.78 ± 0.14, 0.90 ± 0.10; 0.85 ± 0.21, 0.89 ± 0.18, 1.08 ± 0.19; 0.99 ± 0.20, 1.05 ± 0.21, 1.25 ± 0.23) as compared with that of rats in group SI immediately after injury (1.74 ± 0.20, with P values below 0.05). The proportion of CD4⁺ to CD8⁺ was significantly higher in rats of group HD than in group MD on PID 7 (P < 0.05), and the proportion was significantly higher in these two groups than in group S at each time point (with P values below 0.05). The proportion of CD4⁺ to CD8⁺ was significantly higher in rats of group MD on PID 14 and group HD at each time point than in group LD (with P values below 0.05). Compared within each group, the proportions of CD3⁺, CD4⁺, CD8⁺ T lymphocytes and the proportion of CD4⁺ to CD8⁺ of rats in groups LD, MD, and HD showed a trend of gradual elevation along with passage of time.

CONCLUSIONSAP can improve the injury to intestinal mucosa and modulate the balance of T lymphocyte subsets in Peyer's patch in a time- and dose-dependent manner, and it can promote s-IgA secretion of intestinal mucosa in a dose-dependent manner.

Animals ; Astragalus Plant ; adverse effects ; Burns ; immunology ; pathology ; physiopathology ; Dose-Response Relationship, Drug ; Immunity, Mucosal ; Immunoglobulin A ; metabolism ; Intestinal Mucosa ; metabolism ; physiology ; Intestine, Small ; metabolism ; Peyer's Patches ; immunology ; physiopathology ; Polysaccharides ; Rats ; Rats, Sprague-Dawley ; Soft Tissue Injuries ; T-Lymphocyte Subsets ; immunology

BACKGROUND/AIMS: We evaluated the long-term outcome and clinical course of patients of nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal injury by performing capsule endoscopy (CE). METHODS: A multicenter retrospective study was conducted using data collected from the CE nationwide database registry, which has been established since 2002. RESULTS: A total of 140 patients (87 males; mean age, 60.6+/-14.8 years) from the CE nationwide database registry (n=2,885) were diagnosed with NSAID-induced small intestinal injury and enrolled in our study. Forty-nine patients (35.0%) presented with a history of aspirin use and an additional 49 (35.0%) were taking NSAIDs without aspirin. The most prominent findings after performing CE were multiple ulcerations (n=82, 58.6%) and erosions or aphthae (n=32, 22.9%). During the follow-up period (mean, 15.9+/-19.0 months; range, 0 to 106 months), NSAID-induced small intestinal injury only recurred in six patients (4.3%). Older age and hypertension were positive predictive factors for recurrence. CONCLUSIONS: These results suggest that the recurrence of NSAID-induced small bowel injury was not frequent in the presence of conservative treatment. Therefore, the initial diagnosis using CE and the medication history are important.
Age Factors ; Aged ; Anti-Inflammatory Agents, Non-Steroidal/*adverse effects ; Aspirin/adverse effects ; *Capsule Endoscopy ; Female ; Humans ; Intestinal Diseases/chemically induced/*pathology ; Intestine, Small/*drug effects/injuries/*pathology ; Male ; Middle Aged ; Recurrence ; Republic of Korea ; Retrospective Studies ; Time Factors ; Ulcer/chemically induced/*pathology

No abstract available.
Anti-Inflammatory Agents, Non-Steroidal/*adverse effects ; *Capsule Endoscopy ; Female ; Humans ; Intestinal Diseases/*pathology ; Intestine, Small/*drug effects/*pathology ; Male ; Ulcer/*pathology

OBJECTIVETo observe the intervention of Dachengqi Granule (DG) on the apoptosis of small intestine smooth muscle cells (SMCs) in rats with multiple organ dysfunction syndrome (MODS) and its mechanisms.

METHODSHealthy 100 adult Wistar rats were randomly divided into the control group (n =20), the MODS model group (n =40), and the DG group (n =40).E. coli suspension was peritoneally injected to rats in the model group and the DG group to establish bacterial peritonitis induced MODS model. DG at 1 mL/100 g was administered by gastrogavage to rats of the DG group, twice daily for 3 successive days. Twenty-four hours after modeling, the proximal segment of intestine was taken and stained by using terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) and immunohistochemistry. Changes of apoptosis quantity of SMCs and the expression of Bcl-2 associated X protein (Bax), B cell lymphoma/leukemia-2 (Bcl-2) and cytochrome c protein (Cyt c) in mitochondrial apoptotic signaling pathway were observed.

RESULTSCompared with the control group, the apoptosis quantity of SMCs and the expression of Bax and Cyt c protein significantly increased, and the expression of Bcl-2 protein significantly decreased in the MODS model group (P <0.01). Compared with the MODS model group, the apoptosis quantity of SMCs and the expression of Bax and Cyt c proteins significantly decreased, and the expression of Bcl-2 protein significantly increased in the DG group (allP <0.01).

CONCLUSIONDG could inhibit apoptosis of SMCs through suppressing activation of mitochondrial apoptotic signaling pathway in intestinal SMCs, thus promoting the recovery of the gastrointestinal motility function in rats with MODS.

Animals ; Apoptosis ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; In Situ Nick-End Labeling ; Intestine, Small ; physiopathology ; Multiple Organ Failure ; drug therapy ; Muscle, Smooth ; physiopathology ; Myocytes, Smooth Muscle ; drug effects ; Plant Extracts ; pharmacology ; therapeutic use ; Proto-Oncogene Proteins c-bcl-2 ; Rats ; Rats, Wistar ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo compare the difference of Euphorbia Pekinensis Radix before and after being processed with vinegar in the toxicity on rat small intestinal crypt epithelial cells IEC-6, and make a preliminary study on the mechanism of detoxication of Euphorbia Pekinensis Radix processed with vinegar.

METHODWith rat small intestinal crypt epithelial cells IEC-6 as the study object, the MTT method was adopted to detect the effect of Euphorbia Pekinensis Radix before and after being processed with vinegar on IEC-6 cell activity. The morphology of cells were observed by the inverted microscope. The down-regulated mitochondrial apoptosis pathway of enterocytes caused by the vinegar processing was analyzed by using the high content screening.

RESULTCompared with the negative control group, the proliferation inhibition experiment showed that Euphorbia Pekinensis Radix showed a relatively high intestinal cell toxicity (P < 0.01). The results of HCS analysis showed that Euphorbia Pekinensis Radix could significantly reduce the cell nucleus Hoechst fluorescence intensity and mitochondria membrane (P < 0.05, P < 0.01), and increase Annexin V-FITC and PI fluorescence intensity and membrane permeability (P < 0.01, P < 0.01, P < 0.01). After being processed with vinegar, compared with Euphorbia Pekinensis Radix groups with different doses, Euphorbia Pekinensis Radix processed with vinegar could significantly decrease the cell proliferation inhibition effect on enterocytes, increase the cell nuclear Hoechst fluorescence intensity and mitochondria membrane (P < 0.05, P < 0.05), and decrease Annexin V-FITC and PI fluorescence intensity and membrane permeability (P < 0.01, P < 0.01, P < 0.05), and showed a certain dose-effect relationship.

CONCLUSIONThe vinegar processing can further reduce the toxicity of Euphorbia Pekinensis Radix on enterocytes. Its possible mechanism can decrease the effect of Euphorbia Pekinensis Radix on the permeability of IEC-6 cell membrane, so as to provide a basis for further explanation of the detoxication mechanism of Euphorbia Pekinensis Radix processed with vinegar.

Acetic Acid ; chemistry ; Animals ; Apoptosis ; drug effects ; Cell Line ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Chemistry, Pharmaceutical ; methods ; Drugs, Chinese Herbal ; chemistry ; toxicity ; Epithelial Cells ; cytology ; drug effects ; Euphorbia ; chemistry ; Intestine, Small ; cytology ; Rats

BACKGROUND/AIMS: The prevalence of peptic ulcer disease has not decreased mainly due to an increase in the use of NSAIDs. This study was conducted in order to determine whether a chronic NSAID-induced gastric inflammation model could be established by repeated administration of NSAID. METHODS: Indomethacin (10 mg/kg) was administered once per week for six weeks in 8- and 26-week rats and animals were sacrificed every week after administration. Gross ulcer index, histologic damage index, myeloperoxidase (MPO) activity, and mucus (glucosamine) levels were measured. Small bowel damage was also evaluated. RESULTS: Gross gastric damage index showed a peak level at three weeks and then decreased slowly in the 26-week indomethacin group. Gastric mucosal glucosamine level increased in both the 8-week (p=0.038) and 26-week groups (p=0.007). In addition, gastric mucosal MPO level decreased in the 8-week group (p=0.018) but did not show a decrease in the 26-week group. Small bowel damage began to occur at three weeks during the schedule and eight of 36 rats (22.2%) died due to perforation or peritonitis of the small bowel in the 8- and 26-week indomethacin groups, respectively. CONCLUSIONS: Due to gastric adaptation and small bowel damage, repeated administration of NSAID to experimental animals may not be an adequate method for establishment of the chronic gastric inflammation model.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*toxicity ; Disease Models, Animal ; Gastric Mucosa/*drug effects/enzymology/pathology ; Glucosamine/metabolism ; Indomethacin/*toxicity ; Intestine, Small/*drug effects/pathology ; Male ; Peroxidase/metabolism ; Rats ; Rats, Sprague-Dawley ; Time Factors