Gastrointestinal toxicity of NSAIDS appears to be due to a “topical” effect and inhibiting of COX-1; where as, selective COX-2 inhibitors show great GI tolerability. The “topical” component in the pathogenic mechanism for damage is thought to involve the uncoupling of mitochondrial oxidative phosphorylation with increasing intestinal permeability. (The "topical" effect may be due to the detergent-like action of NSAIDs, with the combination of their lipid soluble component and acidity.)The increase in permeability leads to mucosal inflammation. This inhibition may cause inflammation to turn into ulcers. COX-2 is thought to suppress PG synthesis in the areas of inflammation, while also controlling constitutive PG synthesis in the GI tract. This idea was tested using Celecoxib, a selective COX-2 inhibitor, and Indomethacin, which is a non-selective acidic COX inhibitor.
Celecoxib did not have a “topical” effect in their experiment assessing mitochondrial functioning, nor did it lead to changes that may be characteristic of uncouplers of oxidative phosphorylation. Indomethacin did both, while causing intestinal ulcers! Celecoxib did not show any significant damage to the small intestines though, and showed a lack of reduction in intestinal PGE; where as, Indomethacin reduced PGE levels 90%. Indomethacin clearly has damaging effects on the intestines, but Celecoxib does not. The combination of its selectivity and absence of a “topical” effect is thought to be the reason. I found this article interesting, as it went more in depth than I did here, in explaining the possible effects of these NSAIDs because many people around the world are on anti-inflammatory medications. Granted these experiments were done in rats, and one drug was shown to not be harmful, many people have complications with anti-inflammatory medications. They can be quite helpful but are they always worth the risk?!
Oh yeah....That gerbil is awesome!
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