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Hydroxyproline, a serum biomarker candidate for gastric ulcer in rats: a comparison study of metabolic analysis of gastric ulcer models induced by ethanol, stress, and aspirin.

Takeuchi K, Ohishi M, Endo K, Suzumura K, Naraoka H, Ohata T, Seki J, Miyamae Y, Honma M, Soga T - Biomark Insights (2014)

Bottom Line: Gastrointestinal symptoms are a common manifestation of adverse drug effects.Biomarkers for these side effects have not been identified and ulcers are now only detectable by endoscopy.While extrapolation to humans requires further study, hydroxyproline can be a new serum biomarker of gastric injury regardless of cause.

View Article: PubMed Central - PubMed

Affiliation: Drug Safety Research Laboratories, Astellas Pharma Inc., Yodogawa-ku, Osaka, Japan.

ABSTRACT
Gastrointestinal symptoms are a common manifestation of adverse drug effects. Non-steroid anti-inflammatory drugs (NSAIDs) are widely prescribed drugs that induce the serious side effect of gastric mucosal ulceration. Biomarkers for these side effects have not been identified and ulcers are now only detectable by endoscopy. We previously identified five metabolites as biomarker candidates for NSAID-induced gastric ulcer using capillary electrophoresis-mass spectrometry (CE-MS)-based metabolomic analysis of serum and stomach from rats. Here, to clarify mechanism of changes and limitations of indications of biomarker candidates, we performed CE-MS-based metabolomic profiling in stomach and serum from rats with gastric ulcers induced by ethanol, stress, and aspirin. The results suggest that a decrease in hydroxyproline reflects the induction of gastric injury and may be useful in identifying gastric ulcer induced by multiple causes. While extrapolation to humans requires further study, hydroxyproline can be a new serum biomarker of gastric injury regardless of cause.

No MeSH data available.


Related in: MedlinePlus

Levels of hydroxyproline, putrescine, and N8-acetylspermidine in stomach.Notes: Data are reported as means ± standard deviation of four or eight animals per group. Asterisks indicate statistically significant differences: **P < 0.01, *P < 0.05.
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f1-bmi-9-2014-061: Levels of hydroxyproline, putrescine, and N8-acetylspermidine in stomach.Notes: Data are reported as means ± standard deviation of four or eight animals per group. Asterisks indicate statistically significant differences: **P < 0.01, *P < 0.05.

Mentions: Metabolites that were changed in all models are summarized in Table 2 and those that were changed in each model are listed in Supplementary Table S2. In all, 57, 39, and 80 metabolites were changed in the ethanol-, stress-, and aspirin-induced models, respectively. A decrease in the level of hydroxyproline and increase in those of putrescine and N8-acetylspermidine were commonly observed in all models. The levels of these metabolites in stomach are shown in Figure 1, and their selected CE-TOF–MS ion electropherograms in Figure 2. Levels of spermine, spermidine, and N1-acetylspermidine, which are related metabolites of putrescine and N8-acetylspermidine, are shown in Figure 3. These polyamines did not increase except aspirin-induced model. Other biomarker candidates reported in our previous study5 did not show a similar change in the ethanol- and stress-induced gastric ulcer models.


Hydroxyproline, a serum biomarker candidate for gastric ulcer in rats: a comparison study of metabolic analysis of gastric ulcer models induced by ethanol, stress, and aspirin.

Takeuchi K, Ohishi M, Endo K, Suzumura K, Naraoka H, Ohata T, Seki J, Miyamae Y, Honma M, Soga T - Biomark Insights (2014)

Levels of hydroxyproline, putrescine, and N8-acetylspermidine in stomach.Notes: Data are reported as means ± standard deviation of four or eight animals per group. Asterisks indicate statistically significant differences: **P < 0.01, *P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4125369&req=5

f1-bmi-9-2014-061: Levels of hydroxyproline, putrescine, and N8-acetylspermidine in stomach.Notes: Data are reported as means ± standard deviation of four or eight animals per group. Asterisks indicate statistically significant differences: **P < 0.01, *P < 0.05.
Mentions: Metabolites that were changed in all models are summarized in Table 2 and those that were changed in each model are listed in Supplementary Table S2. In all, 57, 39, and 80 metabolites were changed in the ethanol-, stress-, and aspirin-induced models, respectively. A decrease in the level of hydroxyproline and increase in those of putrescine and N8-acetylspermidine were commonly observed in all models. The levels of these metabolites in stomach are shown in Figure 1, and their selected CE-TOF–MS ion electropherograms in Figure 2. Levels of spermine, spermidine, and N1-acetylspermidine, which are related metabolites of putrescine and N8-acetylspermidine, are shown in Figure 3. These polyamines did not increase except aspirin-induced model. Other biomarker candidates reported in our previous study5 did not show a similar change in the ethanol- and stress-induced gastric ulcer models.

Bottom Line: Gastrointestinal symptoms are a common manifestation of adverse drug effects.Biomarkers for these side effects have not been identified and ulcers are now only detectable by endoscopy.While extrapolation to humans requires further study, hydroxyproline can be a new serum biomarker of gastric injury regardless of cause.

View Article: PubMed Central - PubMed

Affiliation: Drug Safety Research Laboratories, Astellas Pharma Inc., Yodogawa-ku, Osaka, Japan.

ABSTRACT
Gastrointestinal symptoms are a common manifestation of adverse drug effects. Non-steroid anti-inflammatory drugs (NSAIDs) are widely prescribed drugs that induce the serious side effect of gastric mucosal ulceration. Biomarkers for these side effects have not been identified and ulcers are now only detectable by endoscopy. We previously identified five metabolites as biomarker candidates for NSAID-induced gastric ulcer using capillary electrophoresis-mass spectrometry (CE-MS)-based metabolomic analysis of serum and stomach from rats. Here, to clarify mechanism of changes and limitations of indications of biomarker candidates, we performed CE-MS-based metabolomic profiling in stomach and serum from rats with gastric ulcers induced by ethanol, stress, and aspirin. The results suggest that a decrease in hydroxyproline reflects the induction of gastric injury and may be useful in identifying gastric ulcer induced by multiple causes. While extrapolation to humans requires further study, hydroxyproline can be a new serum biomarker of gastric injury regardless of cause.

No MeSH data available.


Related in: MedlinePlus