Protective effects of a leukotriene inhibitor in an experimental massive hepatic cell necrosis model.

When heat-killed Propionibacterium acnes was intravenously injected into mice and seven days later, a small amount of gram-negative lipopolysaccharide was also intravenously injected, most of them died of massive hepatic cell necrosis. However, when azelastine hydrochloride, a leukotriene antagonist chemically known as 1(2H)-phthalazinone, 4-[(4-chlorophenyl)methyl]-2-(hexahydro-1-methyl-1H-azepine-4-yl)-, monohydrochloride, or AA861, 2-(12-hydroxydodeca-5, 10-diynyl)-3,5,6-trimethyl-1, 4-benzoquinone, a specific inhibitor of 5-lipoxygenase, was administered during this experimental induction of massive hepatic cell necrosis, the survival rate of the mice increased and the histological changes of the liver improved remarkably. These results suggested that leukotriene may be important for the induction of massive hepatic cell necrosis in our experimental model.