COX expression and PGE(2) and PGD(2) production in experimental acute and chronic gastric lesions.
Prostaglandin E(2) and D(2) (PGE(2) and PGD(2)) production and cyclooxygenase-2 (COX-2) expression during the resolution of acute and chronic gastric inflammatory lesions in Wistar rats have been investigated. Differences between ibuprofen, nonselective COX inhibitor, and rofecoxib, specific COX-2 inhibitor, on the development of the induced responses were also analysed. In an acute model, by instillation of HCL, the greatest injury was observed early with a rapid and progressive restoration. Maximal up-regulation of COX-2 protein was detected at 6 h and was accompanied by increase of PGE(2) synthesis but not PGD(2). Both drugs stimulated COX-2 expression in accordance to their capacity of inhibiting this enzymatic activity, driving to delay in the healing. In a chronic model, by acetic acid-induced gastric ulcers, COX-2 was expressed at 7 days and was also associated with PGE(2) increase. Ibuprofen and rofecoxib also augmented COX-2 protein and inhibited PGE(2) levels. However, PGD(2) production was augmented when none signal of COX-2 protein could be detected. Together, this study confirms the role played by COX-2 enzyme in the resolution of acute and chronic gastric inflammatory process, PGE(2) being the principal product. The antiinflammatory effect of nonsteroidal antiinflammatory drugs (NSAIDs) could be mediated not only through the inhibition of COX activity but also through the induction of antiinflammatory PGs production-such as PGD(2)-although further studies would be needed to clarify the mechanisms of this activity and the possible implicated processes.
Motilva
Virginia
V
Department of Pharmacology, Faculty of Pharmacy, University of Seville, Spain. motilva@us.es
Alarcón de la Lastra
Catalina
C
Bruseghini
Leo
L
Manuel Herrerias
Juan
J
Sánchez-Fidalgo
Susana
S
D019342:Acetic Acid / Q000633:toxicity; D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000633:toxicity; D015232:Dinoprostone / Q000096:biosynthesis*; D004195:Disease Models, Animal; D006851:Hydrochloric Acid / Q000633:toxicity; D007052:Ibuprofen / Q000633:toxicity; D007783:Lactones / Q000633:toxicity; D008297:Male; D008565:Membrane Proteins; D015230:Prostaglandin D2 / Q000096:biosynthesis*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism; D013450:Sulfones / Q000633:toxicity
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D008565:Membrane Proteins; D013450:Sulfones; C116926:rofecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D015232:Dinoprostone; D019342:Acetic Acid; D006851:Hydrochloric Acid; D015230:Prostaglandin D2; D007052:Ibuprofen