Inhibition of 5-lipoxygenase pathway attenuates acute liver failure by inhibiting macrophage activation

This study aimed to investigate the role of 5-lipoxygenase (5-lo) in acute liver failure (alf) and changes in macrophage activation by blocking it. 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 hr 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-). 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 hr after d-galn/lps injection. simultaneously,the microstructure of macrophages was changed most significantly and macrophages counts were increased significantly. moreover,serum tnf- 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. © 2014 lu li et al.