Journal article
Heme oxygenase-1 is protective against nonsteroidal anti-inflammatory drug-induced gastric ulcers
Journal of pediatric gastroenterology and nutrition, Vol.54(4), pp.471-476
04/2012
DOI: 10.1097/MPG.0b013e3182334fdf
PMID: 21873894
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the treatment of pain, fever, and inflammation. Long-term use of these drugs is associated with significant gastric injury. Activated neutrophils and oxidative stress seem to play a significant role in NSAID-induced gastric mucosal damage. The objective of our study is to examine the protective effects of an antioxidant and anti-inflammatory enzyme, heme oxygenase-1 (HO-1), in NSAID-induced gastric injury.
Mice were intraperitoneally injected with indomethacin (10 mg/kg) or sham. A specific inducer of HO-1, cobalt protoporphyrin (5 mg/kg), was given 24 hours before indomethacin to allow for the expression of HO-1. Controls received sham treatment. Twenty-four hours after indomethacin injection, gastric tissue damage was examined with histology. HO-1 expression was measured with immunoblot; cytokine levels were measured with enzyme-linked immunosorbent assay. Neutrophil infiltration was quantified with myeloperoxidase assay. Using electron paramagnetic resonance and desferrioxamine, we measured the labile iron pool in the mouse stomach as a marker of oxidative stress.
Indomethacin caused gastric inflammation and ulcers, neutrophil activation, and increased tissue expression of interleukin-6 and tumor necrosis factor-alpha in mice. Inducing HO-1 with cobalt protoporphyrin reduced gastric inflammation, number of stomach ulcers, tissue neutrophil activation, and proinflammatory cytokine expression caused by indomethacin.
These findings suggest that the induction of an anti-inflammatory and cytoprotective enzyme HO-1 may be a strategy to overcome the gastrointestinal adverse effects limiting the use of NSAIDs.
Details
- Title: Subtitle
- Heme oxygenase-1 is protective against nonsteroidal anti-inflammatory drug-induced gastric ulcers
- Creators
- Aliye Uc - Department of Pediatrics, University of Iowa Carver College of Medicine,200 Hawkins Dr, Iowa City, IA 52242, USA. aliye-uc@uiowa.eduXiaoyan ZhuBrett A WagnerGarry R BuettnerDaniel J Berg
- Resource Type
- Journal article
- Publication Details
- Journal of pediatric gastroenterology and nutrition, Vol.54(4), pp.471-476
- Publisher
- United States
- DOI
- 10.1097/MPG.0b013e3182334fdf
- PMID
- 21873894
- ISSN
- 0277-2116
- eISSN
- 1536-4801
- Language
- English
- Date published
- 04/2012
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Stead Family Department of Pediatrics; Radiation Oncology; Gastroenterology, Hepatology, Pancreatology, and Nutrition; Internal Medicine
- Record Identifier
- 9984046812602771
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