{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:24:27Z","timestamp":1772065467762,"version":"3.50.1"},"reference-count":34,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[1999,11,1]]},"abstract":"<jats:p>Novel aspirin (ASA)-triggered 15-epi-lipoxins (ATL) comprise new potent bioactive eicosanoids that may contribute to the therapeutic effect of this drug. ATL biosynthesis is initiated by ASA acetylation of cyclooxygenase (COX)-2 and was originally identified during the interaction of leukocytes with either endothelial or epithelial cells. Here, we examined ATL biosynthesis in rat hepatocytes either alone or in coincubation with nonparenchymal liver cells (NPC) and in liver homogenates from ASA-treated rats. Rat hepatocytes and CC-1 cells, a rat hepatocyte cell line, displayed COX-1 but not COX-2 mRNA expression and predominantly produced thromboxane A<jats:sub>2<\/jats:sub>(TXA<jats:sub>2<\/jats:sub>) and 15-hydroxyeicosatetraenoic acid (15-HETE). In these cells, ASA shifted the arachidonic acid metabolism from TXA<jats:sub>2<\/jats:sub>to 15-HETE in a concentration-dependent manner. In contrast, neither indomethacin, ibuprofen, valeryl salicylate, nor nimesulide was able to trigger 15-HETE biosynthesis. SKF-525A, a cytochrome P-450 inhibitor, significantly reduced the effect of ASA on 15-HETE biosynthesis. Furthermore, phenobarbital, a potent inducer of cytochrome P-450 activity, further increased ASA-induced 15-HETE production. ASA treatment of hepatocyte-NPC coincubations resulted in the generation of significant amounts of ATL. In addition, in vivo experiments demonstrated augmented hepatic levels of 15-epi-lipoxin A<jats:sub>4<\/jats:sub>in ASA-treated rats. Taken together and considering that ASA is hydrolyzed on its first pass through the portal circulation, these data indicate that, during ASA's consumption, liver tissue generates biologically relevant amounts of ATL by COX-2-independent mechanisms.<\/jats:p>","DOI":"10.1152\/ajpcell.1999.277.5.c870","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T22:35:46Z","timestamp":1514154946000},"page":"C870-C877","source":"Crossref","is-referenced-by-count":41,"title":["Hepatocytes are a rich source of novel aspirin-triggered 15-epi-lipoxin A<sub>4<\/sub>"],"prefix":"10.1152","volume":"277","author":[{"given":"Esther","family":"Titos","sequence":"first","affiliation":[{"name":"DNA Unit and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Chiang","sequence":"additional","affiliation":[{"name":"Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles N.","family":"Serhan","sequence":"additional","affiliation":[{"name":"Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Romano","sequence":"additional","affiliation":[{"name":"Istituto di Patologia Medica e Medicina Mediterranea, University of Messina, Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan","family":"Gaya","sequence":"additional","affiliation":[{"name":"Hormonal Laboratory, Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer, Hospital Cl\u0131\u0301nic and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria","family":"Pueyo","sequence":"additional","affiliation":[{"name":"Qu\u0131\u0301mica Farmac\u00e9utica Bayer (Consumer Care Division), Barcelona 08036, Spain;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan","family":"Cl\u00e0ria","sequence":"additional","affiliation":[{"name":"DNA Unit and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/S0022-3565(25)21674-3","volume":"226","author":"Ali B.","year":"1983","journal-title":"J. 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