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ALF was induced in rats by administration of D-galactosamine (D-GalN)\/lipopolysaccharide (LPS). Rats were injected intraperitoneally with AA-861 (a specific 5-LO inhibitor), 24\u2009hr before D-GalN\/LPS administration. After D-GalN\/LPS injection, the liver tissue was collected for assessment of histology, macrophage microstructure, macrophage counts, 5-LO mRNA formation, protein expression, and concentration of leukotrienes. Serum was collected for detecting alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (Tbil), and tumor necrosis factor- (TNF-)<jats:italic><jats:italic>\u03b1<\/jats:italic><\/jats:italic>. Twenty-four hours after injection, compared with controls, ALF rats were characterized by widespread hepatocyte necrosis and elevated ALT, AST, and Tbil, and 5-LO protein expression reached a peak. Liver leukotriene B4 was also significantly elevated. However, 5-LO mRNA reached a peak 8\u2009hr after D-GalN\/LPS injection. Simultaneously, the microstructure of macrophages was changed most significantly and macrophages counts were increased significantly. Moreover, serum TNF-<jats:italic><jats:italic>\u03b1<\/jats:italic><\/jats:italic>was also elevated. By contrast, AA-861 pretreatment significantly decreased liver necrosis as well as all of the parameters compared with the rats without pretreatment. Macrophages, via the 5-LO pathway, play a critical role in ALF, and 5-LO inhibitor significantly alleviates ALF, possibly related to macrophage inhibition.<\/jats:p>","DOI":"10.1155\/2014\/697560","type":"journal-article","created":{"date-parts":[[2014,6,1]],"date-time":"2014-06-01T21:12:07Z","timestamp":1401657127000},"page":"1-9","source":"Crossref","is-referenced-by-count":13,"title":["Inhibition of 5-Lipoxygenase Pathway Attenuates Acute Liver Failure by Inhibiting Macrophage Activation"],"prefix":"10.1155","volume":"2014","author":[{"given":"Lu","family":"Li","sequence":"first","affiliation":[{"name":"Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Rong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Toxic Hepatic Diseases, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, 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