The effect of indomethacin on the secretion of human salivary epidermal growth factor.
Ulceration associated with nonsteroidal anti-inflammatory drug (NSAID) use is a common problem in elderly patients. The postulated cause of NSAID ulceration is multifactorial but is probably related to the inhibition of the cyclo-oxygenase pathway and a subsequent decrease in mucosal prostaglandin levels. Epidermal growth factor (EGF), on the other hand, has been shown to be gastroprotective, stimulating DNA synthesis, and preventing ASA-induced gastric ulceration. Since EGF is important in gastric mucosal protection, we questioned whether the potential ulcerogenic properties of indomethacin were related in part to decreasing salivary EGF. Twenty healthy male volunteers with no gastrointestinal complaints received indomethacin 50 mg P.O. t.i.d. for 3 consecutive days. Saliva and serum were collected before indomethacin treatment and repeated 2 h after the last indomethacin dose. Stimulated salivary samples were collected for 15 min in fasted subjects and assayed for EGF, whereas serum indomethacin levels were determined by high-performance liquid chromatography. EGF levels significantly decreased by 33% after indomethacin (p < 0.03), and this decrement was linearly related to serum indomethacin concentrations (r = 0.58; p < 0.048). Salivary output did not change after indomethacin treatment. Based on this data, we concluded that indomethacin's ulcerogenic properties may be related to its prostaglandin inhibitory properties as well as its ability to decrease salivary EGF output.
Gilchrist
W
W
Department of Medicine, Walter Reed Army Medical Center, Washington, DC.
Burkhalter
E
E
Eaton
C
C
Schaudies
R P
RP
Maydonovitch
C
C
Andrada
F
F
Maged
A R
AR
Wong
R K
RK
D000328:Adult; D004311:Double-Blind Method; D004815:Epidermal Growth Factor / Q000378:metabolism*; D006801:Humans; D007213:Indomethacin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D012463:Saliva / Q000378:metabolism*
D004815:Epidermal Growth Factor; D007213:Indomethacin