Comparison of Toxicity of Celecoxib vs. Indomethacin

There have been several factors that can lead to the damage of the gastrointestinal tract from NSAID's. There are two main mechanisms for the damage, one involves a the uncoupling of mitochondrial oxidative phosphorylation while the other is the inhibition of COX-1. For the peer review articles this week, it was suggested that the inhibition of COX-2 would suppress the prostaglandin synthesis at the sites of inflammation. To research this, the study used selective COX-2 inhibitors such as Celecoxib and Refecoxib while using Indomethiacin as the positive control in experimental rats.
The rats were treated with the drugs and such factors that were observed were in vitro which measured the liver mitochondria, in vivo which was measured through electron microscopy, intestinal permeability which was measured in urine excretion, the granulocyte marker protein which was taken by faecal samples, Intestinal prostaglandin determination which was taken by freezing the small bowel of the rat in liquid nitrogen and the prostaglandin was extracted from the sample and measured, and finally macroscopic damage which was done by performing a laparotomy on the rats and recording the amount of ulcers that were present upon dissection.
The results after gathering and assessing all the data was that the selective COX-2 inhibitor (Celecoxib) had no significant damage on the small intestine mucosa when compared to Indomethacin. This was probably due to the significantly less reduction that Celecoxib had on PGE levels when compared to Indomethacin which had a 90% reduction in PGE levels. Also to note is that Celecoxib did not lead to physiologic changes which is common with uncouplers of oxidative phosphorylation while Indomethacin showed all parameters of pathophysiologic changes and also caused intestinal ulcers which were present during the laparotomy. To summarize, when compared to Indomethacin, the Celecoxib showed no association with intestinal toxicity in the given study models.