Role of lipoxygenases and the lipoxin A(4)/annexin 1 receptor in ischemia-reperfusion-induced gastric mucosal damage in rats.
Rat gastric mucosal damage was induced by ischemia-reperfusion. The 5-lipoxygenase inhibitors MK886 and A63162, the 12-lipoxygenase inhibitor baicalein, the 15-lipoxygenase inhibitor PD146176 and the lipoxin (LX) A(4)/annexin 1 antagonist Boc1 increased mucosal damage in a dose-dependent manner. Low doses of these compounds, which have no effects on mucosal integrity, cause severe damage when combined with low doses of indomethacin, celecoxib or dexamethasone. 16,16-Dimethylprostaglandin (PG) E(2) and LXA(4) can replace each other in preventing mucosal injury induced by either cyclooxygenase or lipoxygenase inhibitors. The results suggest that not only cyclooxygenases, but also lipoxygenases have a role in limiting gastric mucosal damage during ischemia-reperfusion.
Peskar
Brigitta M
BM
Department of Experimental Clinical Medicine, Ruhr University of Bochum, Bochum, Germany. brigitta.m.peskar@rub.de
Ehrlich
Karlheinz
K
Schuligoi
Rufina
R
Peskar
Bernhard A
BA
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D017302:Annexins / Q000378:metabolism*; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D044950:Flavanones / Q000494:pharmacology; D005449:Fluorenes / Q000494:pharmacology; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D005938:Glucocorticoids / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008084:Lipoxygenase / Q000502:physiology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010647:Phenyl Ethers; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044042:Receptors, Formyl Peptide / Q000502:physiology*; D044067:Receptors, Lipoxin / Q000037:antagonists & inhibitors / Q000502:physiology*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology; D002722:Chlorobenzenes
D015064:16,16-Dimethylprostaglandin E2; D000081:Acetamides; D017302:Annexins; D000897:Anti-Ulcer Agents; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors; D003907:Dexamethasone; D044950:Flavanones; D005449:Fluorenes; D005938:Glucocorticoids; D007211:Indoles; D007213:Indomethacin; D008084:Lipoxygenase; D016859:Lipoxygenase Inhibitors; D009842:Oligopeptides; D010647:Phenyl Ethers; D011448:Prostaglandin Antagonists; D011720:Pyrazoles; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D013449:Sulfonamides; C106248:6,11-dihydro-5-thia-11-aza-benzo(a)-fluorene; C482540:lipoxin A(4) receptor, rat; C068663:N-hydroxy-N-(1-(4-(phenylmethoxy)phenyl)ethyl)-acetamide; C060893:MK-886; D002722:Chlorobenzenes; C006680:baicalein; C046832:t-butyloxycarbonyl-methionyl-leucyl-phenylalanine