The Vioxx Gastrointestinal Outcomes Research (VIGOR) trial, published in 2000, was the first to raise concerns that NSAIDs (specifically, the COX-2 selective inhibitor
rofecoxib) might be associated with a higher risk for cardiovascular (CV) events.
MK801 (Sigma Chemical, St Louis, MO, USA; 0.01, 0.1, 1 [micro]M), a NMDA receptor antagonist; NS398 (1, 10, and 100 [micro]M), a COX-2 selective inhibitor
; DKK-1 (R&D Systems; 10, 50, 100ng/ml), a Wnt/[beta]-catenin signaling inhibitor; and bevacizumab (0.25, 2.5, and 25mg/ml), an anti-VEGF antibody were intravitreally injected with the 80 nmol NMDA in some rats.
To observe whether or not the higher expression of COX-2 contributed to H/R-induced cell injury in H9C2 cardiomyocytes, the cells were incubated with the COX-2 selective inhibitor
, NS398, before being subjected to H/R.
Celecoxib is known as the first COX-2 selective inhibitor
. It was used as a positive control for studying anti-COX-2 mediated anticancer activity.
Based on these observations, the transcriptional level of genes involved in death processes was investigated in H9c2 cells treated with the COX-2 selective inhibitor
. The results showed no major changes in Bax and caspase genes along with a modulatory effect at the transcriptional level for Bcl2 and c-fos genes, which suggests the involvement of those two genes in molecular mechanisms that are probably facilitating cell death.
MEDAL involved more than 34,000 patients with rheumatoid arthritis or osteoarthritis who were randomized to receive treatment with either the COX-2 selective inhibitor
etoricoxib or diclofenac.
They found that there were significantly fewer upper gastrointestinal clinical events with the COX-2 selective inhibitor
etoricoxib than with the traditional NSAID diclofenac due to a decrease in uncomplicated events, but not in the more serious complicated events.
More importantly, inhibition of COX-2 activity using the COX-2 selective inhibitor
, NS398 results in a dose-dependent attenuation of A[beta]-induced cell death (Fig.
Cox-2 selective inhibitor
is a form of NSAID that directly targets cyclooxygenase-2, an enzyme responsible for inflammation and pain and devoid of side effects of Cox-1 enzyme inhibition like less gastrointestinal toxicity and no effects on platelet aggregation.
In theory a COX-2 selective inhibitor
should have the benefits of tocolysis without these side effects, said Dr.
In those with a risk for GI bleeding, an NSAID in combination with misoprostol or a proton pump inhibitor or a COX-2 selective inhibitor
, such as celecoxib, rofecoxib, or valdecoxib, is appropriate.