{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:35:03Z","timestamp":1777433703044,"version":"3.51.4"},"reference-count":61,"publisher":"SAGE Publications","issue":"17","license":[{"start":{"date-parts":[[2013,12,1]],"date-time":"2013-12-01T00:00:00Z","timestamp":1385856000000},"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":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Aim:<\/jats:italic>\n                    <\/jats:bold>\n                    <jats:sc>l<\/jats:sc>\n                    -ascorbic acid (vitamin C) insufficiency is considered one of the major risk factors for the development of liver disease. However, its specific effects and related mechanisms\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    are largely unknown. The objective of this study was to investigate the\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    protective role of vitamin C and its related mechanisms in liver injury with\n                    <jats:italic toggle=\"yes\">Gulo(\u2212\/\u2212)<\/jats:italic>\n                    mice that cannot synthesize vitamin C like humans due to the lack of\n                    <jats:sc>l<\/jats:sc>\n                    -gulonolactone-\u03b3-oxidase (Gulo), an essential enzyme for vitamin C synthesis.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Results:<\/jats:italic>\n                    <\/jats:bold>\n                    When liver injury was induced in\n                    <jats:italic toggle=\"yes\">Gulo(\u2212\/\u2212)<\/jats:italic>\n                    mice by injection of concanavalin A (Con A), there was greater extensive liver damage accompanied by an increased number of apoptotic hepatocytes in vitamin C-insufficient\n                    <jats:italic toggle=\"yes\">Gulo(\u2212\/\u2212)<\/jats:italic>\n                    mice. Additionally, the plasma and hepatic levels of the proinflammatory cytokines, such as TNF-\u03b1 and IFN-\u03b3, were much higher in the vitamin C-insufficient\n                    <jats:italic toggle=\"yes\">Gulo(\u2212\/\u2212)<\/jats:italic>\n                    mice than in the control mice. Moreover, increased numbers of liver-infiltrating T-cells in the vitamin C-insufficient\n                    <jats:italic toggle=\"yes\">Gulo(\u2212\/\u2212)<\/jats:italic>\n                    mice were related to the increased hepatic levels of IFN-inducible factor (IP-10). Although the vitamin C-insufficient\n                    <jats:italic toggle=\"yes\">Gulo(\u2212\/\u2212)<\/jats:italic>\n                    mice had higher amounts of interleukin-22 (IL-22), a hepatoprotective cytokine, a defect in IL-22R\u03b1 expression and its downstream STAT3 activation in hepatocytes were found.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Innovation:<\/jats:italic>\n                    <\/jats:bold>\n                    We first demonstrate the novel\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    action mechanisms of vitamin C on the prevention of disease development in the liver, through the regulation of excessive immune activation and maintenance of the IL-22R\u03b1 signaling pathways.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    <\/jats:bold>\n                    These results suggest that severe liver damage induced by inflammation could be prevented by sufficient supplementation with vitamin C.\n                    <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                    19, 2040\u20132053.\n                  <\/jats:p>","DOI":"10.1089\/ars.2012.4756","type":"journal-article","created":{"date-parts":[[2013,3,10]],"date-time":"2013-03-10T03:38:52Z","timestamp":1362886732000},"page":"2040-2053","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":25,"title":["<i>In Vivo<\/i>\n                    Consequence of Vitamin C Insufficiency in Liver Injury: Vitamin C Ameliorates T-Cell-Mediated Acute Liver Injury in\n                    <i>Gulo(\u2212\/\u2212)<\/i>\n                    Mice"],"prefix":"10.1177","volume":"19","author":[{"given":"Seyeon","family":"Bae","sequence":"first","affiliation":[{"name":"Seoul National University College of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chung-Hyun","family":"Cho","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyemin","family":"Kim","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yejin","family":"Kim","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang-Rae","family":"Kim","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-il","family":"Hwang","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung Hwan","family":"Yoon","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Seung","family":"Kang","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wang Jae","family":"Lee","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2013,12,10]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.35.3.317"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(94)90108-2"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2168.1999.01182.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2008.04.006"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.124.3232.1148.b"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(59)90232-3"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.66.6.981"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62060-3"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2008.03634.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3182120cb8"},{"key":"e_1_3_3_12_2","first-page":"92","article-title":"Cytokines, STATs and liver disease","volume":"2","author":"Gao B","year":"2005","unstructured":"Gao B. 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