The risk of upper gastrointestinal complications (including dyspepsia, gastritis and heartburn) was significantly increased with COX-2 inhibitors versus placebo (RR 1.19, 95% CI 1.03-1.38; I<sup>2</sup> = 0%), particularly for abdominal pain, which increased by 40% with COX-2 inhibitors (RR 1.40, 95% CI 1.08-1.80; I<sup>2</sup> = 0%).
The protective effect was associated with decreased lipid peroxidation, increased prostaglandin E<sub>2</sub>, reduction in gastric acidity and reduction in COX-2 mRNA expression which was altered by stress.
Moreover, the induction of COX-2 by chenodeoxycholate was enhanced by acidity in a dose-dependent manner, and the promoter activity of COX-2 was increased by chenodeoxycholate in SNU-1041, a human laryngeal cancer cell line, whereas the transcription of COX-2 was inhibited by actinomycin-D.