Urine metabolomics of rats with chronic atrophic gastritis.

BACKGROUND/AIM: To use liquid chromatography-mass spectrometry (LC-MS) to identify endogenous differential metabolites in the urine of rats with chronic atrophic gastritis (CAG). MATERIALS AND METHODS: Methylnitronitrosoguanidine (MNNG) was used to produce a CAG model in Wistar rats, and HE staining was used to determine the pathological model. LC-MS was used to detect the differential metabolic profiles in rat urine. Diversified analysis was performed by the statistical method. RESULTS: Compared with the control group, the model group had 68 differential metabolites, 25 that were upregulated and 43 that were downregulated. The main metabolic pathways were D-glutamine and D-glutamic acid metabolism, histidine metabolism and purine metabolism. CONCLUSION: By searching for differential metabolites and metabolic pathways in the urine of CAG rats, this study provides effective experimental data for the pathogenesis and clinical diagnosis of CAG.

Urinary metabolomics research for Huangqi Jianzhong Tang against chronic atrophic gastritis rats based on 1 H NMR and UPLC-Q/TOF MS.

OBJECTIVES: As a traditional Chinese medicine (TCM), Huangqi Jianzhong Tang (HQJZ) has a good efficacy in treating chronic atrophic gastritis (CAG). Our objective was to determine its mechanism based on the urine comprehensive metabolome. METHODS: In the study, a metabolomic approach was applied to reveal the efficacy of HQJZ on the constructed CAG rats coupled with proton nuclear magnetic resonance (1 H NMR) and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS). KEY FINDINGS: The results showed the regulatory effect of HQJZ on urinary metabolism disorder in CAG rats was similar to the positive drug teprenone. Nineteen and 16 potential biomarkers related to CAG were detected by NMR and UPLC-Q/TOF MS, respectively. Thirty-two urine metabolites were significantly regulated by HQJZ treatment. Combined with MetPA and partial least square regression analysis (PLS-RA), three metabolic pathways of valine, leucine and isoleucine, TCA cycle, and glycine, serine and threonine metabolism were the most relevant pathways for HQJZ treatment. CONCLUSIONS: The main mechanism of HQJZ might be due to the balance of energy consumption, inflammatory inhibition, improvement of the immune system and oxidative stress on the constructed CAG rats. These findings provided comprehensive metabolic information of TCM by parallel measurements by LC-MS and NMR.

Material basis research for Huangqi Jianzhong Tang against chronic atrophic gastritis rats through integration of urinary metabonomics and SystemsDock.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqi Jianzhong Tang (HQJZ), a celebrated traditional Chinese medicine (TCM), is commonly used for treatment of chronic atrophic gastritis (CAG) in China. AIM OF THE STUDY: We aimed to screen out the material basis of HQJZ against CAG. MATERIALS AND METHODS: CAG rat model was constructed by alternant administrations of ammonia solution and sodium deoxycholate, and the hunger disorder method. Body weight, biochemical indexes and histopathological exam were used to evaluate the efficacy of HQJZ. 1H NMR-based metabonomics was employed to analyze the urine metabolic features of HQJZ deviated from CAG rats. SystemsDock analysis was utilized to explore the active compounds involved into the efficacy of HQJZ against CAG based on the targeted metabolic biomarkers. RESULTS: The metabonomic results indicated that HQJZ could significantly improve 16 urinary perturbed metabolites in CAG rats, which were involved into the metabolism of energy and amino acids. And then 28 related proteins and genes were selected out to be the potential targets of HQJZ against CAG based on the six key metabolites closely correlating with biochemical indexes (α-ketoglutarate, valine, sarcosine, glycine, malonate and fumarate). 71 previous identified compounds were docked through systemsDock-aided molecular docking experiments. And the constructed herb-component-protein-metabolite interaction network (HCPMN) revealed the associations between the herbal formulae and CAG. At last, 51 compounds of them were screened as promising active constitutes for the inhibition of CAG, which could act on various targeted proteins. CONCLUSIONS: he results showed that the approach integrating of metabonomics and systemsDock is a powerful tool to obtain the material basis and regulatory mechanism of TCM formula.

NMR-based metabonomics and correlation analysis reveal potential biomarkers associated with chronic atrophic gastritis.

Chronic atrophic gastritis (CAG) is one of the most important pre-cancerous states with a high prevalence. Exploring of the underlying mechanism and potential biomarkers is of significant importance for CAG. In the present work, 1H NMR-based metabonomics with correlative analysis was performed to analyze the metabolic features of CAG. 19 plasma metabolites and 18 urine metabolites were enrolled to construct the circulatory and excretory metabolome of CAG, which was in response to alterations of energy metabolism, inflammation, immune dysfunction, as well as oxidative stress. 7 plasma biomarkers and 7 urine biomarkers were screened to elucidate the pathogenesis of CAG based on the further correlation analysis with biochemical indexes. Finally, 3 plasma biomarkers (arginine, succinate and 3-hydroxybutyrate) and 2 urine biomarkers (α-ketoglutarate and valine) highlighted the potential to indicate risks of CAG in virtue of correlation with pepsin activity and ROC analysis. Here, our results paved a way for elucidating the underlying mechanisms in the development of CAG, and provided new avenues for the diagnosis of CAG and presented potential drug targets for treatment of CAG.

ECP-EURONUT-Intestinal Metaplasia Study: urinary and gastric juice analyses.

In an international multi-centre study of diet and precancerous lesions of the stomach, 24 h urine samples were analysed from 133 sets of patients with intestinal metaplasia (IM) and their matched controls from the UK, 14 sets of cases and controls from Portugal and 22 sets from Poland. In addition, urine aliquots (but not 24 h volumes) were available from 12 matched sets from Greece and 19 from Croatia. There was no difference between cases and controls in the daily urinary excretion (as a measure of daily intake) of sodium or nitrate but the potassium output by patients with IM was significantly lower than that of the controls in the UK and Portugal, and the ratio Na/K was higher in patients with IM than in controls in the UK and Portugal, but not in Poland, Greece or Croatia. Gastric juice samples were analysed from 133 sets of IM patients and endoscoped controls from the UK and 22 sets from Croatia. When compared with the endoscoped controls, IM patients from both countries had a significantly higher proportion of gastric juice samples containing bacteria and nitrite and with a pH > 6. The results are discussed in relation to current hypotheses on gastric carcinogenesis.

N-nitrosoproline excretion in the presence and absence of gastric disease.

N-nitrosoproline (NPRO) excretion, an indicator of endogenous nitrosation, was measured in a group of hospital inpatients who were identified by endoscopy and gastric biopsy as either having gastric lesions or having healthy stomachs. NPRO was assayed in background 24-hour urine samples and samples collected after loading doses of nitrate and L-proline. The presence of gastric lesions was associated with altered gastric pH and concomitant changes in gastric juice nitrate and nitrite concentration. Gastric juice pH increased with increasing severity of gastric disease (P = 0.031) and patients with normal stomachs had a lower gastric pH than those with chronic atrophic gastritis (CAG) (3.0 vs. 6.5, P = 0.017). The changes in gastric juice nitrate concentration were in the reverse direction (P = 0.002 for trend) with normal patients having higher mean levels than CAG patients (12.7 vs. 5.5 micrograms/ml, P less than 0.0001). Nitrite concentration increased with severity of gastric disease but the results were not significant (normal, 82.9 vs. CAG, 223.4 ng/ml, P = 0.069). No association was found between the presence of gastric lesions and increased urinary NPRO excretion. Mutagenic activity was not detected in any of the gastric juice samples.