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Pharmacological correction of stress-induced gastric ulceration by novel small-molecule agents with antioxidant profile.

Kudryavtsev KV, Markevich AO, Virchenko OV, Falalyeyeva TM, Beregova TV, Ostapchenko LI, Zabolotnev DV, Zefirov NS - ScientificWorldJournal (2014)

Bottom Line: Prophylactic single-dose 1 mg/kg treatment with (2-hydroxyphenyl)thioacetyl derivatives of L-lysine and L-proline efficiently decreases up to 86% stress-induced stomach ulceration in rats.Discovered small-molecule antiulcer agents modulate activities of gastric mucosa tissue superoxide dismutase, catalase, and xanthine oxidase in concerted directions.Gastroprotective effect of (2-hydroxyphenyl)thioacetyl derivatives of L-lysine and L-proline at least partially depends on the correction of gastric mucosa oxidative balance.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, M.V. Lomonosov Moscow State University, Moscow 119991, Russia ; Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka 142432, Russia.

ABSTRACT
This study was designed to determine novel small-molecule agents influencing the pathogenesis of gastric lesions induced by stress. To achieve this goal, four novel organic compounds containing structural fragments with known antioxidant activity were synthesized, characterized by physicochemical methods, and evaluated in vivo at water immersion restraint conditions. The levels of lipid peroxidation products and activities of antioxidative system enzymes were measured in gastric mucosa and correlated with the observed gastroprotective activity of the active compounds. Prophylactic single-dose 1 mg/kg treatment with (2-hydroxyphenyl)thioacetyl derivatives of L-lysine and L-proline efficiently decreases up to 86% stress-induced stomach ulceration in rats. Discovered small-molecule antiulcer agents modulate activities of gastric mucosa tissue superoxide dismutase, catalase, and xanthine oxidase in concerted directions. Gastroprotective effect of (2-hydroxyphenyl)thioacetyl derivatives of L-lysine and L-proline at least partially depends on the correction of gastric mucosa oxidative balance.

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Related in: MedlinePlus

The influence of small-molecule agents 1, 2, 3, and 4 (dose 1 mg/kg, intraperitoneally) on the area of gastric mucosa ulceration caused by stress in rats: II: stress-control group; III: stress-control group treated with aqueous DMSO (10 μL of DMSO in 1 mL of saline); IV: compound 1; V: compound 2 in aqueous DMSO; VI: compound 3; VII: compound 4 in aqueous DMSO. *P < 0.05; **P < 0.01; ***P < 0.001.
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fig2: The influence of small-molecule agents 1, 2, 3, and 4 (dose 1 mg/kg, intraperitoneally) on the area of gastric mucosa ulceration caused by stress in rats: II: stress-control group; III: stress-control group treated with aqueous DMSO (10 μL of DMSO in 1 mL of saline); IV: compound 1; V: compound 2 in aqueous DMSO; VI: compound 3; VII: compound 4 in aqueous DMSO. *P < 0.05; **P < 0.01; ***P < 0.001.

Mentions: The intact control (sham) group I rats had no stomach injuries under analysis. WIRS during 3 hours caused the development of ulcers (area 12.25 ± 2.14 mm2 per stomach), erosions (length 0.66 ± 0.6 mm), and hemorrhages (2.5 ± 0.32 points) in GM in the stress-control group II (Figure 2). Development of injuries was accompanied by intensification of LPO that was displayed by the increase of diene conjugates by 59.0% (P < 0.01), TBARS by 139.0% (P < 0.01), and Schiff bases by 59.0% (P < 0.01) in the stress-control group II against the intact control group I (Table 1). Analysis of enzymatic activity of the stress-control group II animals revealed increase of catalase activity by 86.1% (P < 0.01) and decrease of SOD and xanthine oxidase activity by 52.6% (P < 0.01) and 38.3% (P < 0.01), respectively, against the sham group I (Table 2). Pretreatment of the animals with dipeptide analog 1 increased the area of WIRS-induced ulcers by 117.0% (P < 0.05) and hemorrhages by 46.7% (P < 0.05) in comparison with the stress-control group II. The injection of compounds 2, 3, and 4 solutions to rats before application of stress led to reducing of the ulcers area by 62.0% (P < 0.05), 74.0% (P < 0.01), and 86.0% (P < 0.001), respectively, compared to group II (Figure 2). The formations of erosions and hemorrhages were not detected under the treatment of rats with the single dose of agents 2, 3, or 4 (corresponding animals groups V, VI, and VII). Amino acid derivatives of (2-hydroxyphenyl)thioacetic acid 3 and 4 were selected for the further investigations as the drugs with the most pronounced cytoprotective properties.


Pharmacological correction of stress-induced gastric ulceration by novel small-molecule agents with antioxidant profile.

Kudryavtsev KV, Markevich AO, Virchenko OV, Falalyeyeva TM, Beregova TV, Ostapchenko LI, Zabolotnev DV, Zefirov NS - ScientificWorldJournal (2014)

The influence of small-molecule agents 1, 2, 3, and 4 (dose 1 mg/kg, intraperitoneally) on the area of gastric mucosa ulceration caused by stress in rats: II: stress-control group; III: stress-control group treated with aqueous DMSO (10 μL of DMSO in 1 mL of saline); IV: compound 1; V: compound 2 in aqueous DMSO; VI: compound 3; VII: compound 4 in aqueous DMSO. *P < 0.05; **P < 0.01; ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3934458&req=5

fig2: The influence of small-molecule agents 1, 2, 3, and 4 (dose 1 mg/kg, intraperitoneally) on the area of gastric mucosa ulceration caused by stress in rats: II: stress-control group; III: stress-control group treated with aqueous DMSO (10 μL of DMSO in 1 mL of saline); IV: compound 1; V: compound 2 in aqueous DMSO; VI: compound 3; VII: compound 4 in aqueous DMSO. *P < 0.05; **P < 0.01; ***P < 0.001.
Mentions: The intact control (sham) group I rats had no stomach injuries under analysis. WIRS during 3 hours caused the development of ulcers (area 12.25 ± 2.14 mm2 per stomach), erosions (length 0.66 ± 0.6 mm), and hemorrhages (2.5 ± 0.32 points) in GM in the stress-control group II (Figure 2). Development of injuries was accompanied by intensification of LPO that was displayed by the increase of diene conjugates by 59.0% (P < 0.01), TBARS by 139.0% (P < 0.01), and Schiff bases by 59.0% (P < 0.01) in the stress-control group II against the intact control group I (Table 1). Analysis of enzymatic activity of the stress-control group II animals revealed increase of catalase activity by 86.1% (P < 0.01) and decrease of SOD and xanthine oxidase activity by 52.6% (P < 0.01) and 38.3% (P < 0.01), respectively, against the sham group I (Table 2). Pretreatment of the animals with dipeptide analog 1 increased the area of WIRS-induced ulcers by 117.0% (P < 0.05) and hemorrhages by 46.7% (P < 0.05) in comparison with the stress-control group II. The injection of compounds 2, 3, and 4 solutions to rats before application of stress led to reducing of the ulcers area by 62.0% (P < 0.05), 74.0% (P < 0.01), and 86.0% (P < 0.001), respectively, compared to group II (Figure 2). The formations of erosions and hemorrhages were not detected under the treatment of rats with the single dose of agents 2, 3, or 4 (corresponding animals groups V, VI, and VII). Amino acid derivatives of (2-hydroxyphenyl)thioacetic acid 3 and 4 were selected for the further investigations as the drugs with the most pronounced cytoprotective properties.

Bottom Line: Prophylactic single-dose 1 mg/kg treatment with (2-hydroxyphenyl)thioacetyl derivatives of L-lysine and L-proline efficiently decreases up to 86% stress-induced stomach ulceration in rats.Discovered small-molecule antiulcer agents modulate activities of gastric mucosa tissue superoxide dismutase, catalase, and xanthine oxidase in concerted directions.Gastroprotective effect of (2-hydroxyphenyl)thioacetyl derivatives of L-lysine and L-proline at least partially depends on the correction of gastric mucosa oxidative balance.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, M.V. Lomonosov Moscow State University, Moscow 119991, Russia ; Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka 142432, Russia.

ABSTRACT
This study was designed to determine novel small-molecule agents influencing the pathogenesis of gastric lesions induced by stress. To achieve this goal, four novel organic compounds containing structural fragments with known antioxidant activity were synthesized, characterized by physicochemical methods, and evaluated in vivo at water immersion restraint conditions. The levels of lipid peroxidation products and activities of antioxidative system enzymes were measured in gastric mucosa and correlated with the observed gastroprotective activity of the active compounds. Prophylactic single-dose 1 mg/kg treatment with (2-hydroxyphenyl)thioacetyl derivatives of L-lysine and L-proline efficiently decreases up to 86% stress-induced stomach ulceration in rats. Discovered small-molecule antiulcer agents modulate activities of gastric mucosa tissue superoxide dismutase, catalase, and xanthine oxidase in concerted directions. Gastroprotective effect of (2-hydroxyphenyl)thioacetyl derivatives of L-lysine and L-proline at least partially depends on the correction of gastric mucosa oxidative balance.

Show MeSH
Related in: MedlinePlus