{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T09:45:37Z","timestamp":1785923137598,"version":"3.56.0"},"reference-count":65,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2012,5,23]],"date-time":"2012-05-23T00:00:00Z","timestamp":1337731200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:p>\n                    c-Jun N-terminal kinase (JNK) activation promotes hepatocyte death during acetaminophen overdose, a common cause of drug-induced liver failure.  While mitogen-activated protein kinase (MAPK) phosphatase (Mkp)-1 is a critical negative regulator of JNK MAPK, little is known about the role of Mkp-1 during hepatotoxicity. In this study, we evaluated the role of Mkp-1 during acute acetaminophen toxicity.\n                    <jats:italic toggle=\"yes\">\n                      Mkp-1\n                      <jats:sup>+\/+<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">\n                      Mkp-1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice were dosed ip with vehicle or acetaminophen at 300 mg\/kg (for mechanistic studies) or 400 mg\/kg (for survival studies). Tissues were collected 1\u20136 hr post 300 mg\/kg dosing to assess glutathione levels, organ damage, and MAPK activation.\n                    <jats:italic toggle=\"yes\">\n                      Mkp-1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice exhibited more rapid plasma clearance of acetaminophen than did\n                    <jats:italic toggle=\"yes\">\n                      Mkp-1\n                      <jats:sup>+\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mice, indicated by a quicker decline of plasma acetaminophen level. Moreover,\n                    <jats:italic toggle=\"yes\">\n                      Mkp-1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice suffered more severe liver injury, indicated by higher plasma alanine transaminase activity and more extensive centrilobular apoptosis and necrosis. Hepatic JNK activity in\n                    <jats:italic toggle=\"yes\">\n                      Mkp-1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice was higher than in\n                    <jats:italic toggle=\"yes\">\n                      Mkp-1\n                      <jats:sup>+\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Finally,\n                    <jats:italic toggle=\"yes\">\n                      Mkp-1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice displayed a lower overall survival rate and shorter median survival time after dosing with 400 mg\/kg acetaminophen. The more severe phenotype exhibited by\n                    <jats:italic toggle=\"yes\">\n                      Mkp-1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice indicates that Mkp-1 plays a protective role during acute acetaminophen overdose, potentially through regulation of JNK.\n                  <\/jats:p>","DOI":"10.1177\/0192623312447551","type":"journal-article","created":{"date-parts":[[2012,5,25]],"date-time":"2012-05-25T17:42:59Z","timestamp":1337967779000},"page":"1095-1105","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":40,"title":["Mitogen-activated Protein Kinase Phosphatase (Mkp)-1 Protects Mice against Acetaminophen-induced Hepatic Injury"],"prefix":"10.1177","volume":"40","author":[{"given":"Lyn M.","family":"Wancket","sequence":"first","affiliation":[{"name":"Department of Veterinary Bioscience, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA"},{"name":"Department of Pediatrics, Center for Perinatal Research, The Research Institute at Nationwide Children\u2019s Hospital, The Ohio State University College of Medicine, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Center for Perinatal Research, The Research Institute at Nationwide Children\u2019s Hospital, The Ohio State University College of Medicine, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynette K.","family":"Rogers","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Center for Perinatal Research, The Research Institute at Nationwide Children\u2019s Hospital, The Ohio State University College of Medicine, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Veterinary Bioscience, The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA"},{"name":"Department of Pediatrics, Center for Perinatal Research, The Research Institute at Nationwide Children\u2019s Hospital, The Ohio State University College of Medicine, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2012,5,23]]},"reference":[{"key":"e_1_3_4_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(25)22134-6"},{"key":"e_1_3_4_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/24.1.58"},{"key":"e_1_3_4_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2010.02219.x"},{"key":"e_1_3_4_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/019262339602400206"},{"key":"e_1_3_4_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.20458"},{"key":"e_1_3_4_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx060228l"},{"key":"e_1_3_4_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2008.02420.x"},{"key":"e_1_3_4_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(77)90522-X"},{"key":"e_1_3_4_10_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.11.6408"},{"key":"e_1_3_4_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510965103"},{"key":"e_1_3_4_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24429"},{"key":"e_1_3_4_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.5.1327"},{"key":"e_1_3_4_14_1","first-page":"925","article-title":"Disruption of the erp\/mkp-1 gene does not affect mouse development: Normal MAP kinase activity in ERP\/MKP-1-deficient fibroblasts","volume":"13","author":"Dorfman K.","year":"1996","unstructured":"Dorfman K., Carrasco D., Gruda M., Ryan C., Lira S. 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