Irritant-induced cyclooxygenase-2 is involved in the defense mechanism of the gastric mucosa in mice.
BACKGROUND
Endogenous and exogenous prostaglandins (PGs) have been shown to contribute to reducing the gastric injury caused by irritants given subsequently. The aim of this study was to clarify whether cyclooxygenase-2 (COX-2) protein induced by pretreatment was involved in the prevention of subsequent ethanol-caused gastric injury in mice.


METHODS
Mice were pretreated with acidified ethanol or saline and then COX-2 protein expression in the stomach was immunohistochemically determined every 8h. Mice were administered 95% ethanol 24h after the acidified ethanol pretreatment, and gastric mucosal damage was evaluated macroscopically and histologically. The effects of NS-398 or indomethacin on the 95% ethanol-caused damage were also examined.


RESULTS
Acidified ethanol pretreatment induced COX-2 protein expression in lamina propria macrophages of the gastric mucosa, with a peak level 24h after the pretreatment. The 95% ethanol treatment caused gastric mucosal damage. The degree of the damage was not different between mice pretreated with acidified ethanol and those pretreated with saline. However, NS-398 aggravated the ethanol-caused damage only in mice pretreated with acidified ethanol, while indomethacin aggravated the damage, evaluated histologically, irrespective of the pretreatment.


CONCLUSIONS
Pretreatment-induced COX-2, in addition to COX-1, seemed to be involved in the defense mechanism through minimizing the damage caused by a subsequent irritant.
Miyake
Kazumasa
K
Third Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Tsukui
Taku
T
Wada
Ken
K
Tatsuguchi
Atsushi
A
Futagami
Seiji
S
Hiratsuka
Tetsuro
T
Shinoki
Kei
K
Iizumi
Tadasu
T
Akamatsu
Tomonori
T
Sakamoto
Choitsu
C
Kobayashi
Masafumi
M
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D019610:Cytoprotection; D000431:Ethanol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology; D007150:Immunohistochemistry / Q000379:methods; D007213:Indomethacin / Q000494:pharmacology; D007509:Irritants / Q000494:pharmacology*; D007527:Isoenzymes / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D023421:Models, Animal; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D013449:Sulfonamides / Q000494:pharmacology
D002492:Central Nervous System Depressants; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007509:Irritants; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D000431:Ethanol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D007213:Indomethacin