Figure 1.
Effects of NSAIDs in rats with adjuvant arthritis.
Despite comparable suppression of paw swelling (panel A), gastric prostaglandin synthesis (panel B) and whole blood thromboxane synthesis (panel C), ATB-346 and NCX 429 did not cause significant gastric (panel D) or intestinal (panel E) damage. Celecoxib also did not cause significant GI damage. *p<0.05, **p<0.01 versus the naproxen-treated group. n = 8 per group.
Figure 2.
Co-administration of naproxen or celecoxib with omeprazole and/or low-dose aspirin results in marked exacerbation of small intestinal damage.
In contrast, rats given a naproxen derivative (ATB-346 or NCX 429) did not develop significant intestinal injury when given alone or in combination with omeprazole, low-dose aspirin, or both. *p<0.05, **p<0.01 versus the corresponding group treated with NSAID alone (n≥6 per group). Aspirin and omeprazole, alone or given together, did not elicit significant intestinal damage.
Figure 3.
Older (19 months of age) rats develop extensive gastric damage when given naproxen, but not when given equimolar doses of a hydrogen sulfide-releasing naproxen derivative (ATB-346) or a nitric oxide-releasing naproxen derivative (NCX 429).
***p<0.001 versus the vehicle-treated group. n = 6 rats per group.
Figure 4.
Increased naproxen-induced small intestinal damage in obese versus lean rats.
Neither lean nor obese rats developed intestinal damage when given ATB-346. **p<0.01 versus the corresponding vehicle- and ATB-346-treated rats. n = 6 rats per group.
Figure 5.
Severity of gastric damage induced by naproxen is similar in spontaneously hypertensive (SHR) and normotensive (WKY) rats.
ATB-346 suppressed gastric prostaglandin (PG)E2 synthesis and whole blood thromboxane (TXB2) synthesis as effectively as naproxen, but did not elicit gastric damage. ***p<0.001 versus the corresponding vehicle-treated group (n = 6 per group).
Figure 6.
Serum and biliary levels of naproxen are significantly reduced in rats given a naproxen derivative (ATB-346 or NCX 429) as compared to the levels observed in rats given an equimolar dose of naproxen itself.
The test drugs were administered twice-daily for 2 days. *p<0.05, **p<0001 versus the naproxen-treated group. n = 4 per group.