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Sterile inflammation, triggered by hepatic damage, facilitates gut bacterial translocation leading to systemic inflammation; TLR4-mediated activation by LPS has been shown to have a critical role in APAP-mediated hepatotoxicity. In this study, we demonstrate significant protection mediated by chitohexaose (Chtx) in mice challenged with a lethal dose of APAP (400 mg\/kg b.w.). Decreased mortality by Chtx was associated with reduced hepatic damage, increased peritoneal migration of neutrophils, decreased mRNA expression of IL-1<jats:italic>\u03b2<\/jats:italic>as well as inhibition of inflammasome activation in liver. Further, an alternate mouse model of co-administration of a sublethal doses of APAP (200\u2009mg\/kg b.w.) and LPS (5\u2009mg\/kg b.w.) operating synergistically and mediating complete mortality was developed. Overwhelming inflammation, characterized by increased inflammatory cytokines (TNF-<jats:italic>\u03b1<\/jats:italic>, IL-1<jats:italic>\u03b2<\/jats:italic>and so on) in liver as well as in circulation and mortality was demonstrable in this model. Also, Chtx administration mediated significant reversal of mortality in APAP+LPS co-administered mice, which was associated with reduced IL-1<jats:italic>\u03b2<\/jats:italic>in liver and plasma cytokines in this model. In conclusion, Chtx being a small molecular weight linear carbohydrate offers promise for clinical management of liver failure associated with APAP overdose.<\/jats:p>","DOI":"10.1038\/cddis.2016.131","type":"journal-article","created":{"date-parts":[[2016,5,12]],"date-time":"2016-05-12T12:47:42Z","timestamp":1463057262000},"page":"e2224-e2224","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Chitohexaose protects against acetaminophen-induced hepatotoxicity in mice"],"prefix":"10.1038","volume":"7","author":[{"given":"P K","family":"Barman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B K","family":"Prusty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Suklabaidya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Senapati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Ravindran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,5,12]]},"reference":[{"key":"BFcddis2016131_CR1","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1016\/j.clinre.2011.03.010","volume":"35","author":"P Ichai","year":"2011","unstructured":"Ichai P, Samuel D . 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