Products of cyclooxygenase (COX)-2 contribute to mucosal defense.
The acetylation of COX-2 by aspirin results in the generation of 15(R)-epi-lipoxin A4. This exerts protective effects in the stomach.
In gastritis, lipoxin A4 may make a greater contribution to mucosal defense.
|Aspirin elicited greater lipoxin synthesis in inflamed stomachs.|
|AJP – Gastrointestinal and Liver Physiology|
In this study, researchers from Canada and Italy tested this hypothesis in rats, using an iodoacetamide-induced gastritis model.
The team added iodoacetamide to drinking water for 5 days. They then gave the rats aspirin, and blindly assessed the extent of gastric damage after 3 hours.
In addition, the researchers determined gastric 15(R)-epi-lipoxin A4 and PGE2 levels.
They also evaluated any effects of pretreatment with the selective COX-2 inhibitor, rofecoxib, and a lipoxin receptor antagonist.
The team used intravital microscopy to examine the effects of aspirin, and the other test drugs, on leukocyte adherence within mesenteric venules.
The researchers found that aspirin elicited greater lipoxin synthesis in inflamed, rather than in normal stomachs. They determined that there was reduced gastric damage.
They also found that rofecoxib inhibited lipoxin synthesis and exacerbated aspirin-induced damage. The lipoxin antagonist also exacerbated aspirin-induced damage.
Dr Marcellus Souza's team concluded, "In rats with gastritis, aspirin reduced leukocyte adherence…and this effect was reversed by rofecoxib or by the lipoxin antagonist".
"These results support the notion that aspirin-triggered lipoxin synthesis via COX-2 makes an important contribution to mucosal defense in both the normal and inflamed stomach".