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Administration of ANIT to mice causes neutrophil\u2010mediated hepatocellular necrosis. Prolonged exposure of mice to ANIT also produces bile duct hyperplasia and liver fibrosis. However, the mechanistic connection between ANIT\u2010induced hepatocellular necrosis and bile duct hyperplasia and fibrosis is not well characterized. We examined impact of two different doses of ANIT, by feeding chow containing ANIT (0.05%, 0.1%), on the severity of various liver pathologies in a model of chronic ANIT exposure. ANIT\u2010elicited increases in liver inflammation and hepatocellular necrosis increased with dose. Remarkably, there was no connection between increased hepatocellular necrosis and bile duct hyperplasia and peribiliary fibrosis, as these pathologies increased similarly in mice exposed to either dose of ANIT. The results indicate that the severity of hepatocellular necrosis does not dictate the extent of bile duct hyperplasia\/fibrosis in ANIT\u2010exposed mice.<\/jats:p>","DOI":"10.1002\/jbt.21834","type":"journal-article","created":{"date-parts":[[2016,9,8]],"date-time":"2016-09-08T07:44:04Z","timestamp":1473320644000},"page":"1-7","source":"Crossref","is-referenced-by-count":18,"title":["Dose\u2010dependent effects of alpha\u2010naphthylisothiocyanate disconnect biliary fibrosis from hepatocellular necrosis"],"prefix":"10.1002","volume":"31","author":[{"given":"Nikita","family":"Joshi","sequence":"first","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology Michigan State University East Lansing MI 48824 USA"},{"name":"Institute for Integrative Toxicology Michigan State University East Lansing MI 48824 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica L.","family":"Ray","sequence":"additional","affiliation":[{"name":"Department of Pathobiology &amp; Diagnostic Investigation Michigan State University East Lansing MI 48824 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna K.","family":"Kopec","sequence":"additional","affiliation":[{"name":"Department of Pathobiology &amp; Diagnostic Investigation Michigan State University East Lansing MI 48824 USA"},{"name":"Institute for Integrative Toxicology Michigan State University East Lansing MI 48824 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James P.","family":"Luyendyk","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology Michigan State University East Lansing MI 48824 USA"},{"name":"Department of Pathobiology &amp; Diagnostic Investigation Michigan State University East Lansing MI 48824 USA"},{"name":"Institute for Integrative Toxicology Michigan State University East Lansing MI 48824 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,9,8]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(65)90125-0"},{"issue":"3","key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0031-6997(25)06713-4","volume":"28","author":"Plaa G. 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