Tag Archives: aspirin

Effect of hydrogen sulfide-releasing aspirin on esophageal and gastric mucosa compromised by stress injury

O. S. Zayachkivska1, N. S. Bula1, Ya. I. Pavlovskiy1, I. O. Pshyk-Titko1,
E. M. Gavriluk1, O. I. Grushka1, J. L. Wallace2,3

1Danylo Halytsky Lviv National Medical University, Ukraine;
2University of Calgary, Canada;
3University of Toronto, Canada;
e-mail: ozayachkivska@gmail.com

Recent data of study H2S in gastrointestinal tract has proven its potent cytoprotection on mucosal defense among acid-related diseases in the gut. The aim was to evaluate the effects of H2S-releasing aspirin derivative (ATB-340) on esophageal and gastric mucosa compromised by stress injury. Rats were treated with vehicle (control), aspirin (10 mg/kg), ATB-340 (17.5 mg/kg) single or 9 days duration, with or without induction of stress injury. Esophageal mucosa, gastric mucosa were estimated by histopathological damage scoring. Serological levels of VCAM-1, IL-6 by ELISA. ATB-340 treatment resulted in protective effect and lower grade of damage score in esophageal mucosa and gastric mucosa lesions vs effect of aspirin in single or 9 days applications. The serum levels of VCAM, IL-6 in rats who were aspirin-treated and subjected to stress-injury were higher than those in control animals. Treatment with ATB-340 produced an anti-inflammatory effect by decreasing VCAM and IL-6 vs aspirin. Cytoprotective effect of ATB-340 on esophageal mucosa and gastric mucosa was modulated by inhibi­ting inflammation and improving endothelial functions.

Redox-sensitive transcription factors EGR-1 and SP1 IN the pathogenesis of experimental gastric ulcer

S. M. Beregovyi1, T. M. Chervinska1, A. S. Dranitsina1,
S. Szabo2, G. M. Tolstanova1

1Educational and Scientific Centre Institute of Biology,
Taras Shevchenko National University of Kyiv, Ukraine;
2University of California, Irvine, USA;
e-mail: gtolstanova@gmail.com

Changes in redox status of gastric mucosa cells are the main pathogenic factor of gastric erosion and gastric ulcer development. Pro-oxidants can affect cell transcription activity via changes in redox-sensitive transcription factors. Egr-1 and Sp-1 may regulate the transcription of genes that are associated with the pathogenesis of gastric ulcer (growth factors, cell cycle regulators, etc.). The aim of the present study was to reveal the possible involvement of zinc-finger transcription factors Egr-1 & Sp-1 in the molecular mechanisms underlying gastric lesions caused by aspirin administration and stress. Gastric ulcer was induced in male rats (180-220 g) by immobilization stress combined with water-immersion (IMO-WI) or aspirin gavage (10 mg/100 g). The rats were euthanized 20 min, 1 hour, or 3 hours following the ulcerogenic factor exposure. Protein expression was determined by Western blot analysis and RT-PCR; levels of SH-groups of proteins were determined by method of Ellman et al. Development of gastric ulcer lesions was associated with twofold (P < 0.05) decrease in concentration of protein SH-groups in the rat gastric mucosa. These changes were accompanied by significant (P < 0.05) increase in the expression of Egr-1 mRNA and protein in both gastric ulcer models, and the changes in IMO-WI were more profound. Increased levels of Egr-1 were associated with the decrease in Sp1 protein levels. We showed for the first time the competitive interaction between redox-sensitive transcription factors Egr-1 and Sp1 in the early phases of gastric ulcer development, which might facilitate inducible transcriptional activity of Egr-1 at the expense of reduction in Sp1 activity.