Effect of omeprazole dose, nonsteroidal anti-inflammatory agents, and smoking on repair mechanisms in acute peptic ulcer bleeding.

Abstract

BACKGROUND:

Peptic ulcer bleeding (PUB) is a major cause of upper gastrointestinal bleeding. The effect of omeprazole on mucosal repair is unknown.

AIMS:

We studied the effect of omeprazole, nonsteroidal anti-inflammatory agents, and smoking on PUB.

METHODS:

There were 43 PUB patients who received regular or high dose of omeprazole for 72 h. Biopsies from antrum and corpus were taken before and after treatment. Biopsy samples from 20 celiac disease patients worked as controls. The expression of Ki-67, Bcl-2, COX-2, Hsp27, and Hsp70 was analyzed from patients and controls.

RESULTS:

Bcl-2 expression in PUB patients was lower than in controls. However, Bcl-2 increased significantly from 5.0 (SD 4.5) to 9.1 % (SD 6.7), p = 0.0004, in the antrum after omeprazole. In univariate analysis, a high omeprazole dose caused a more profound increase in Ki-67 expression in the corpus: 35.3 % (SD 54.8) than a regular dose: -10.1 % (SD 40.6), p = 0.022. In multivariate analysis, Ki-67 decreased significantly in the corpus between the pre- and posttreatment period (p = 0.011), while a high omeprazole dose (p = 0.0265), the use of NSAIDs (p = 0.0208), and smoking (p = 0.0296) significantly increased Ki-67 expression. Bcl-2 in the corpus increased significantly (p = 0.0003) after treatment.

CONCLUSIONS:

Our findings suggest that Bcl-2 may be an important factor in the pathogenesis of a peptic ulcer and PUB. In addition, high-dose omeprazole increased the expression of Ki-67, which may enhance the healing process of a peptic ulcer.

• Authors: Tuomo Rantanen, Marianne Udd, Teemu Honkanen, Pekka Miettinen, Vesa Kärjä, Lassi Rantanen, Risto Julkunen, Harri Mustonen, Timo Paavonen, Niku Oksala
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 59 Issue 11 Pg. 2666-74 (Nov 2014) ISSN: 1573-2568 [Electronic] United States
• PMID: 25138901 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Anti-Ulcer Agents
• HSP27 Heat-Shock Proteins
• HSP70 Heat-Shock Proteins
• Ki-67 Antigen
• Proto-Oncogene Proteins c-bcl-2
• Cyclooxygenase 2
• PTGS2 protein, human
• Omeprazole

Topics

• Adult
• Aged
• Anti-Inflammatory Agents, Non-Steroidal (adverse effects)
• Anti-Ulcer Agents (administration & dosage, therapeutic use)
• Cyclooxygenase 2 (genetics, metabolism)
• Dose-Response Relationship, Drug
• Female
• Gene Expression Regulation
• HSP27 Heat-Shock Proteins (genetics, metabolism)
• HSP70 Heat-Shock Proteins (genetics, metabolism)
• Humans
• Ki-67 Antigen (genetics, metabolism)
• Male
• Middle Aged
• Omeprazole (administration & dosage, therapeutic use)
• Peptic Ulcer Hemorrhage (chemically induced, pathology)
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• Smoking (adverse effects)