{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:51:57Z","timestamp":1788828717542,"version":"build-2803163510"},"reference-count":53,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T00:00:00Z","timestamp":1233273600000},"content-version":"vor","delay-in-days":1247,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2005,9]]},"abstract":"<jats:p><jats:list list-type=\"explicit-label\"><jats:list-item><jats:p>Diabetes mellitus leads to a high incidence of several so\u2010called complications, sharing similar pathophysiological features in several territories. Previous reports points at early nonenzymatic glycosylation products (Amadori adducts) as mediators of diabetic vascular complications. In the present study, we analysed a possible role for Amadori adducts as stimulators of proinflammatory pathways in human peritoneal mesothelial cells (HPMCs).<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Cultured HPMCs isolated from 13 different patients (mean age 38.7\u00b116 years) were exposed to different Amadori adducts, that is, highly glycated haemoglobin (10\u2003n<jats:sc>M<\/jats:sc>) and glycated bovine serum albumin (0.25\u2003mg\u2003ml<jats:sup>\u22121<\/jats:sup>), as well as to their respective low glycosylation controls. Amadori adducts, but not their respective controls, elicited a marked increase of NF\u2010<jats:italic>\u03ba<\/jats:italic>B activation, as determined by electromobility shift assays and transient transfection experiments.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Additionally, Amadori adducts significantly increased the production of NF\u2010<jats:italic>\u03ba<\/jats:italic>B\u2010related proinflammatory molecules, including cytokines, such as TNF\u2010<jats:italic>\u03b1<\/jats:italic>, IL\u20101<jats:italic>\u03b2<\/jats:italic>or IL\u20106, and enzymes, such as cyclooxygenase\u20102 and inducible nitric oxide (NO) synthase, this latter leading to the release of NO by HPMCs.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>The effects of Amadori adducts were mediated by different reactive oxygen and nitrosative species (e.g. superoxide anions, hydroxyl radicals, and peroxynitrite), as they were blunted by coincubation with the appropriate scavengers. Furthermore, NO generated upon exposure to Amadori adducts further stimulated NF\u2010<jats:italic>\u03ba<\/jats:italic>B activation, either directly or after combination with superoxide anions to form peroxynitrite.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>We conclude that Amadori adducts can favour peritoneal inflammation by exacerbating changes in NO synthesis pathway and triggering NF\u2010<jats:italic>\u03ba<\/jats:italic>B\u2010related proinflammatory signals in human mesothelial cells.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic>(2005)<jats:bold>146<\/jats:bold>, 268\u2013279. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706309\">10.1038\/sj.bjp.0706309<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0706309","type":"journal-article","created":{"date-parts":[[2005,7,4]],"date-time":"2005-07-04T15:46:28Z","timestamp":1120491988000},"page":"268-279","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Amadori adducts activate nuclear factor\u2010<i>\u03ba<\/i>B\u2010related proinflammatory genes in cultured human peritoneal mesothelial cells"],"prefix":"10.1111","volume":"146","author":[{"given":"Juli\u00e1n","family":"Nevado","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concepci\u00f3n","family":"Peir\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Vallejo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"El\u2010Assar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Lafuente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Matesanz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Azcutia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Cercas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos F","family":"S\u00e1nchez\u2010Ferrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leocadio","family":"Rodr\u00edguez\u2010Ma\u00f1as","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1997.4"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.28.4.583"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.6.3285"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00157.2001"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2002.00115.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115014"},{"key":"e_1_2_8_8_1","first-page":"73","article-title":"Role of advanced glycosylation products in complications of diabetes","volume":"1","author":"CERAMI A.","year":"1988","journal-title":"Diabetes Care"},{"key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1177\/089686080002000631","article-title":"Human peritoneal mesothelial cells produce nitric oxide: induction by cytokines","volume":"20","author":"CHEN J.Y.","year":"2000","journal-title":"Periton. 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