Dexamethasone impairs the gastric mucosal integrity in rats treated with a cyclooxygenase-1 but not with a cyclooxygenase-2 inhibitor.
In rats, neither the cyclooxygenase-1 inhibitor SC-560 nor the cyclooxygenase-2 inhibitor rofecoxib damages the gastric mucosa. Coadministration of dexamethasone induced injury in SC-560- but not in rofecoxib-treated rats. High levels of cyclooxygenase-1 protein occurred in the gastric mucosa of control rats, with no change after administration of SC-560. In contrast, the gastric cyclooxygenase-2 protein levels were low in control rats, but increased in a time-dependent manner after administration of SC-560. Dexamethasone prevented the increase in cyclooxygenase-2 protein levels. Our findings show that inhibition of cyclooxygenase-1 upregulates cyclooxygenase-2. When the upregulation is prevented by dexamethasone, gastric damage develops, suggesting that induction of cyclooxygenase-2 represents a compensatory mechanism that counteracts the injurious effect of cyclooxygenase-1 inhibition.
Peskar
Brigitta M
BM
Department of Experimental Clinical Medicine, Ruhr-University Bochum, Bochum, Germany. brigitta.m.peskar@rub.de
Ehrlich
Karlheinz
K
Egger
Tamara
T
Sattler
Wolfgang
W
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D051545:Cyclooxygenase 1 / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D003907:Dexamethasone / Q000009:adverse effects*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D007783:Lactones / Q000009:adverse effects; D008297:Male; D011720:Pyrazoles / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D013450:Sulfones / Q000009:adverse effects; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D011720:Pyrazoles; C115461:SC 560; D013450:Sulfones; C116926:rofecoxib; D003907:Dexamethasone; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2