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The lack of inhibition of COX\u20102 by paracetamol in inflamed tissues and thereby the lack of anti\u2010inflammatory activity has been attributed to high lipid hydroperoxide (LHP) tone. In this study, we demonstrate that the inhibition of the diclofenac\u2010induced COX\u20102 activity in J774.2 cells by paracetamol is not related to the intracellular LHP tone as paracetamol inhibited this activity in the absence and presence of T\u2010butyl hydroperoxide, which is an LHP donor, to the same extents. In fact, treatment of the cells with diclofenac resulted in an increase in the LHP tone. Stimulation of the cells with lipopolysaccharide (LPS) results in the induction of a COX\u20102 activity, which was not inhibited by paracetamol. This represents the classical induction pathway for COX\u20102. LPS stimulation did not alter the LHP tone. These results suggest that the enzymatic activity of the diclofenac\u2010induced COX\u20102 protein does not depend on the supply of hydroperoxides to its peroxidase active site.<\/jats:p>","DOI":"10.1111\/j.1472-8206.2010.00842.x","type":"journal-article","created":{"date-parts":[[2010,6,22]],"date-time":"2010-06-22T09:15:47Z","timestamp":1277198147000},"page":"186-190","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Inhibition of the diclofenac\u2010induced cyclooxygenase\u20102 activity by paracetamol in cultured macrophages is not related to the intracellular lipid hydroperoxide tone"],"prefix":"10.1111","volume":"25","author":[{"given":"Samir S.","family":"Ayoub","sequence":"first","affiliation":[]},{"given":"Amrish","family":"Joshi","sequence":"additional","affiliation":[]},{"given":"Mary","family":"Chol","sequence":"additional","affiliation":[]},{"given":"Derek W.","family":"Gilroy","sequence":"additional","affiliation":[]},{"given":"Michael P.","family":"Seed","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2011,3,9]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1034"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.24.11693"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/240410a0"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199907000-00032"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1972.tb06887.x"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2006.03.061"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.4.5574.264"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.33.4.353"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(82)90565-2"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1367-5931(00)00130-7"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.102588199"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.2000.2232"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.6.3275"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-009-0048-y"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-2437fje"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-8015com"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/9550"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.61.5.997"}],"container-title":["Fundamental &amp; Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1472-8206.2010.00842.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1472-8206.2010.00842.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,15]],"date-time":"2023-10-15T16:55:19Z","timestamp":1697388919000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1472-8206.2010.00842.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,3,9]]},"references-count":18,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2011,4]]}},"alternative-id":["10.1111\/j.1472-8206.2010.00842.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1472-8206.2010.00842.x","archive":["Portico"],"relation":{},"ISSN":["0767-3981","1472-8206"],"issn-type":[{"value":"0767-3981","type":"print"},{"value":"1472-8206","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,3,9]]},"assertion":[{"value":"2011-03-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}