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It has been hypothesized that the interaction between a drug and modest inflammation results in a decreased threshold for drug toxicity. In this study, we tested the hypothesis that INH causes liver injury in rats when coadministered with lipopolysaccharide (LPS). Neither INH nor LPS alone caused liver injury. The coadministration of INH and LPS was associated with increases in serum and histopathological markers of liver injury. Tumour necrosis factor\u2010\u03b1 expression was significantly increased in the coadministered group. The downregulation of the bile acid transporter, bile salt export pump, and multidrug resistance protein 2 at both mRNA and protein levels was observed. Furthermore, the level of Farnesoid X receptor, which regulates the bile salt export pump and multidrug resistance protein 2, were clearly decreased. These results indicate that the coadministration of nontoxic doses of LPS and INH causes liver injury; the disruption of biliary excretion is considered the primary inflammation\u2010related characteristic of INH\u2010induced hepatotoxicity. Copyright \u00a9 2014 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.2979","type":"journal-article","created":{"date-parts":[[2014,2,6]],"date-time":"2014-02-06T08:02:49Z","timestamp":1391673769000},"page":"1436-1442","source":"Crossref","is-referenced-by-count":19,"title":["Lipopolysaccharide exposure augments isoniazide\u2010induced liver injury"],"prefix":"10.1002","volume":"34","author":[{"given":"Yijing","family":"Su","sequence":"first","affiliation":[{"name":"Jiangsu Center of Drug Screening China Pharmaceutical University  24 Tong Jia Xiang Nanjing 210009 Jiangsu Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Biology Institute of Shandong Academy of Sciences  19 Keyuan Road, Lixia District Jinan 250014 Shandong Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi.","family":"Chen","sequence":"additional","affiliation":[{"name":"Jiangsu Center of Drug Screening China Pharmaceutical University  24 Tong Jia Xiang Nanjing 210009 Jiangsu Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhou","family":"Jiang","sequence":"additional","affiliation":[{"name":"Jiangsu Center of Drug Screening China Pharmaceutical University  24 Tong Jia Xiang Nanjing 210009 Jiangsu Province People's Republic of China"},{"name":"Key Laboratory of Drug Quality Control and Pharmacovigilance China Pharmaceutical University  24 Tong Jia Xiang Nanjing 210009 Jiangsu Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixin","family":"Sun","sequence":"additional","affiliation":[{"name":"Jiangsu Center of Drug Screening China Pharmaceutical University  24 Tong Jia Xiang Nanjing 210009 Jiangsu Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Center of Drug Screening China Pharmaceutical University  24 Tong Jia Xiang Nanjing 210009 Jiangsu Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Center of Drug Screening China Pharmaceutical University  24 Tong Jia Xiang Nanjing 210009 Jiangsu Province People's Republic of China"},{"name":"JiangSu Center for Pharmacodynamics Research and Evaluation China Pharmaceutical University  24 Tong Jia Xiang Nanjing 210009 Jiangsu Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,2,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2012.658041"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/55.2.444"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1240002"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/595078"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1980.60.2.303"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R900010-JLR200"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr300430u"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.109.001727"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00071.2004"},{"key":"e_1_2_7_11_1","first-page":"11","article-title":"Effects of bacterial endotoxin on drug pharmacokinetics","volume":"62","author":"Hasegawa T","year":"1999","journal-title":"Nagoya. 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