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Ninety-six mice were randomly divided into the control (<jats:italic>n<\/jats:italic>\u2009=\u20098), CQ (<jats:italic>n<\/jats:italic>\u2009=\u20098), CCl<jats:sub>4<\/jats:sub> (<jats:italic>n<\/jats:italic>\u2009=\u200940), and CCl<jats:sub>4<\/jats:sub>\u2009+\u2009CQ (<jats:italic>n<\/jats:italic>\u2009=\u200940) treatment groups. In the CCl<jats:sub>4<\/jats:sub> group, mice were intraperitoneally (i.p) injected with 0.3% CCl<jats:sub>4<\/jats:sub> (10\u2009mL\/kg, dissolved in olive oil); in the CCl<jats:sub>4<\/jats:sub>\u2009+\u2009CQ group, mice were i.p injected with CQ at 50\u2009mg\/kg at 2, 24, and 48\u2009h before CCl<jats:sub>4<\/jats:sub> administration. The mice in the control and CQ groups were administered with an equal vehicle or CQ (50\u2009mg\/kg). Mice were killed at 2, 6, 12, 24, 48\u2009h post CCl<jats:sub>4<\/jats:sub> treatment and their livers were harvested for analysis. The results showed that CQ pre-treatment markedly inhibited CCl<jats:sub>4<\/jats:sub>-induced acute liver injury, which was evidenced by decreased serum transaminase, aspartate transaminase and lower histological scores of liver injury. CQ pretreatment downregulated the CCl<jats:sub>4<\/jats:sub>-induced hepatic tissue expression of high-mobility group box 1 (HMGB1) and the levels of serum HMGB1 as well as IL-6 and TNF-\u03b1. Furthermore, CQ pre-treatment inhibited autophagy, downregulated NF-kB expression, upregulated p53 expression, increased the ratio of Bax\/Bcl-2, and increased the activation of caspase-3 in hepatic tissue. This is the first study to demonstrate that CQ ameliorates CCl<jats:sub>4<\/jats:sub>-induced acute liver injury via the inhibition of HMGB1-mediated inflammatory responses and the stimulation of pro-apoptotic pathways to modulate the apoptotic and inflammatory responses associated with progress of liver damage.<\/jats:p>","DOI":"10.1038\/s41419-018-1136-2","type":"journal-article","created":{"date-parts":[[2018,11,26]],"date-time":"2018-11-26T12:04:22Z","timestamp":1543233862000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":171,"title":["Chloroquine ameliorates carbon tetrachloride-induced acute liver injury in mice via the concomitant inhibition of inflammation and induction of apoptosis"],"prefix":"10.1038","volume":"9","author":[{"given":"Chongshan","family":"Dai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xilong","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daowen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun","family":"Tun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Velkov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shusheng","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,11,26]]},"reference":[{"key":"1136_CR1","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1038\/nrm1489","volume":"5","author":"R Taub","year":"2004","unstructured":"Taub, R. 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