{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T19:00:45Z","timestamp":1760295645845,"version":"3.37.3"},"reference-count":12,"publisher":"Wiley","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2010-0003277"],"award-info":[{"award-number":["NRF-2010-0003277"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007687","name":"Korean Diabetes Association","doi-asserted-by":"publisher","award":["NRF-2010-0003277"],"award-info":[{"award-number":["NRF-2010-0003277"]}],"id":[{"id":"10.13039\/100007687","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Diabetes Research"],"published-print":{"date-parts":[[2012]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>. Pentoxifylline (PTX) anti-TNF properties are known to exert hepatoprotective effects in various liver injury models. The aim of this study was to investigate whether PTX has beneficial roles in the development of methionine- and choline-deficient-(MCD-) diet-induced NAFLD SD rats<jats:italic>in vivo<\/jats:italic>and TNF-<jats:italic>\u03b1<\/jats:italic>-induced Hep3B cells<jats:italic>in vitro<\/jats:italic>.<jats:italic>Methods<\/jats:italic>. SD Rats were classified according to diet (chow or MCD diet) and treatment (normal saline or PTX injection) over a period of 4 weeks: group I (chow + saline,<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mi>n<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>4<\/mml:mn><\/mml:math>), group II (chow + PTX), group III (MCD + saline), and group IV (MCD + PTX). Hep3B cells were treated with 100\u2009ng\/ml TNF-<jats:italic>\u03b1<\/jats:italic>(24\u2009h) in the absence or presence of PTX (1\u2009mM).<jats:italic>Results<\/jats:italic>. PTX attenuated MCD-diet-induced serum ALT levels and hepatic steatosis. In real-time PCR and western blotting analysis, PTX decreased MCD-diet-induced TNF-alpha mRNA expression and proapoptotic unfolded protein response by ER stress (GRP78, p-eIF2, ATF4, IRE1<jats:italic>\u03b1<\/jats:italic>, CHOP, and p-JNK activation)<jats:italic>in vivo<\/jats:italic>. PTX (1\u2009mM) reduced TNF-<jats:italic>\u03b1<\/jats:italic>-induced activation of GRP78, p-eIF2, ATF4, IRE1<jats:italic>\u03b1<\/jats:italic>, and CHOP<jats:italic>in vitro<\/jats:italic>.<jats:italic>Conclusion<\/jats:italic>. PTX has beneficial roles in the development of MCD-diet-induced steatohepatitis through partial suppression of TNF-<jats:italic>\u03b1<\/jats:italic>and ER stress.<\/jats:p>","DOI":"10.1155\/2012\/762565","type":"journal-article","created":{"date-parts":[[2012,1,29]],"date-time":"2012-01-29T16:01:25Z","timestamp":1327852885000},"page":"1-8","source":"Crossref","is-referenced-by-count":16,"title":["Pentoxifylline Attenuates Methionine- and Choline-Deficient-Diet-Induced Steatohepatitis by Suppressing TNF-<b><i>\u03b1<\/i><\/b>Expression and Endoplasmic Reticulum Stress"],"prefix":"10.1155","volume":"2012","author":[{"given":"Min Kyung","family":"Chae","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Gyu","family":"Park","sequence":"additional","affiliation":[{"name":"College of Biomedical Sciences, CHA University, Seongnam 463-836, Republic of Korea"},{"name":"Advanced Institutes of Convergence Technology (AICT), Seoul National University, Suwon 443-270, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun-Ok","family":"Song","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun Seok","family":"Kang","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bong Soo","family":"Cha","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun Chul","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byung-Wan","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra011775"},{"issue":"2","key":"2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.4093\/dmj.2011.35.2.101","volume":"35","year":"2011","journal-title":"Diabetes Metabolism Journal"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29069"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-008-9058-1"},{"issue":"1","key":"5","first-page":"39","volume":"16","year":"2007","journal-title":"Journal of Gastrointestinal and Liver Diseases"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50316"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1186\/1476-511X-10-49"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.922"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.52"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2006.04756.x"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1055\/s-0028-1091980"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.10.039"}],"container-title":["Experimental Diabetes Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/jdr\/2012\/762565.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/jdr\/2012\/762565.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/jdr\/2012\/762565.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2017,6,20]],"date-time":"2017-06-20T09:28:24Z","timestamp":1497950904000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.hindawi.com\/journals\/jdr\/2012\/762565\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012]]},"references-count":12,"alternative-id":["762565","762565"],"URL":"https:\/\/doi.org\/10.1155\/2012\/762565","relation":{},"ISSN":["1687-5214","1687-5303"],"issn-type":[{"type":"print","value":"1687-5214"},{"type":"electronic","value":"1687-5303"}],"subject":[],"published":{"date-parts":[[2012]]}}}