{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T04:37:44Z","timestamp":1767155864386,"version":"build-2238731810"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,2,2]],"date-time":"2009-02-02T00:00:00Z","timestamp":1233532800000},"content-version":"vor","delay-in-days":2558,"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":[[2002,2]]},"abstract":"<jats:p>\n                    <jats:list list-type=\"explicit-label\">\n                      <jats:list-item>\n                        <jats:p>NCX\u2010701 is a nitric oxide (NO)\u2010releasing acetaminophen (APAP) derivative.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>In the present study we demonstrated that NCX\u2010701 is as effective as APAP in controlling body temperature in a rat model of endotoxin\u2010induced fever.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          Liver toxicity is a major complication of APAP overdosing. To investigate whether NCX\u2010701 is hepatotoxic, BALB\/C mice were injected with 100\u2003\u2013\u2003500\u2003mg\u2003kg\n                          <jats:sup>\u22121<\/jats:sup>\n                          APAP or NCX\u2010701 alone or in combination (i.e. 500\u2003mg\u2003kg\n                          <jats:sup>\u22121<\/jats:sup>\n                          of both compounds). Our results demonstrated that although APAP caused a dose\u2010dependent liver injury, NCX\u2010701 was completely devoid of liver toxicity. At the dose of 500\u2003mg\u2003kg\n                          <jats:sup>\u22121<\/jats:sup>\n                          APAP caused an \u223c40 fold increase of AST plasma levels and extensive centrilobular necrosis.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>APAP and NCX\u2010701 share the same metabolic pathway as demonstrated by the time\u2010course of APAP\u2010glucuronide concentrations in plasma and liver.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          NCX\u2010701 was safe in mice with pre\u2010existing chronic liver disease. Indeed, while C57BL6 transgenic mice expressing the hepatitis B virus (HBV) at the age of 8 months were significantly more susceptible to liver damage induced by APAP (500\u2003mg\u2003kg\n                          <jats:sup>\u22121<\/jats:sup>\n                          ) than their congenic littermates, treating HBV\u2010transgenic mice with NCX\u2010701, 500\u2003mg\u2003kg\n                          <jats:sup>\u22121<\/jats:sup>\n                          , caused no damage.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          Co\u2010administration of NCX\u2010701 at the dose 500\u2003mg\u2003kg\n                          <jats:sup>\u22121<\/jats:sup>\n                          to mice treated with APAP, 500\u2003mg\u2003kg\n                          <jats:sup>\u22121<\/jats:sup>\n                          , completely protected against liver damage induced by APAP.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          APAP, but not NCX\u2010701, upregulated liver Fas and Fas Ligand mRNA expression\n                          <jats:italic>in vivo<\/jats:italic>\n                          . Incubating mouse hepatocytes with APAP, but not with NCX\u2010701, increased cell surface Fas expression and sensitized hepatocytes to death induced by challenge with a Fas\u2010agonistic antibody.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Collectively, these observations suggest that APAP toxicity is Fas mediated and that NCX\u2010701 spares the liver by acting at several checkpoints in the Fas pathway.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>British Journal of Pharmacology<\/jats:italic>\n                    (2002)\n                    <jats:bold>135<\/jats:bold>\n                    , 589\u2013599; doi:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0704500\">10.1038\/sj.bjp.0704500<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1038\/sj.bjp.0704500","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T16:43:10Z","timestamp":1106930590000},"page":"589-599","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["A NO\u2010releasing derivative of acetaminophen spares the liver by acting at several checkpoints in the Fas pathway \u2028THIS ARTICLE HAS BEEN RETRACTED"],"prefix":"10.1111","volume":"135","author":[{"given":"Stefano","family":"Fiorucci","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Antonelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Mencarelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Palazzetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorena","family":"Alvarez\u2010Miller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo","family":"Muscara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piero","family":"Del Soldato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Sanpaolo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John L","family":"Wallace","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Morelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(93)90201-7"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703509"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/taap.1995.1125"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1553-2712.1999.tb00113.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/48.2.264"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.316.7146.1724"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.5.1327"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.11.6365"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(95)90341-0"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.313.7070.1417"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI4765"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70012-0"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70223-X"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.1999.00442.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703837"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510270316"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.10.6158-6169.1995"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/jech.51.2.175"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.168.1.43"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.3109\/03602539509029816"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-483X(97)00061-9"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.7.921"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0497-409"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-483X(98)00046-8"},{"key":"e_1_2_7_26_1","first-page":"1072","article-title":"Nitric oxide and acetaminophen\u2010mediated oxidative injury: modulation of interleukin\u20101\u2010induced nitric oxide synthesis in cultured rat hepatocytes","volume":"282","author":"KUO P.C.","year":"1997","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/54.2.509"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1006\/taap.1999.8635"},{"key":"e_1_2_7_29_1","first-page":"G1069","article-title":"Nitric Oxide IV. Determinants of nitric oxide protection and toxicity in liver","volume":"276","author":"LI J.","year":"1999","journal-title":"Am. J. Physiol."},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1522-7146(1996)11:1<11::AID-JBT2>3.0.CO;2-Y"},{"key":"e_1_2_7_31_1","first-page":"580","article-title":"Metallothionein\u2010I\/II knockout mice are sensitive to acetaminophen\u2010induced hepatotoxicity","volume":"289","author":"LIU J.","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510300104"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.15.10349"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/3276"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02354-0"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02342-4"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.317.7173.1609"},{"key":"e_1_2_7_38_1","first-page":"519","article-title":"Effect of N\u2010acetylcysteine on heat shock protein induction by acetaminophen in mouse liver","volume":"286","author":"SALMINEN W.F.","year":"1998","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199710163371602"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2000.278.6.G992"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80111-9"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02355-2"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118338"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.49.31138"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/78475"}],"updated-by":[{"DOI":"10.1111\/j.1476-5381.2009.00272.x","type":"retraction","label":"Retraction","source":"retraction-watch","updated":{"date-parts":[[2009,3,1]],"date-time":"2009-03-01T00:00:00Z","timestamp":1235865600000},"record-id":"1473"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0704500","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0704500","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0704500","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T21:58:01Z","timestamp":1697493481000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0704500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,2]]},"references-count":44,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2002,2]]}},"alternative-id":["10.1038\/sj.bjp.0704500"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0704500","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,2]]},"assertion":[{"value":"2009-02-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}