Skip Navigation LinksHome > April 2012 - Volume 54 - Issue 4 > Heme Oxygenase-1 Is Protective Against Nonsteroidal Anti-inf...
Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0b013e3182334fdf
Original Articles: Gastroenterology

Heme Oxygenase-1 Is Protective Against Nonsteroidal Anti-inflammatory Drug–induced Gastric Ulcers

Uc, Aliye*; Zhu, Xiaoyan*; Wagner, Brett A.; Buettner, Garry R.; Berg, Daniel J.

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Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Copyright 2012 by ESPGHAN and NASPGHAN


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