Suppression of lipopolysaccharide-induced tumor necrosis factor-release and liver injury in mice by naringin

Suppressive effects of naringin on lipopolysaccharide-induced tumor necrosi s factor (TNF) release followed by liver injury were investigated. Intraper itoneal (i.p.) treatment with naringin prior to an intravenous (i.v.) chall enge of lipopolysaccharide significantly reduced serum TNF levels in a dose -dependent manner and was the most effective when administered 60 min prior to lipopolysaccharide challenge. Treatment with naringin 3 h prior to lipo polysaccharide challenge resulted in complete protection from lipopolysacch aride lethality in D-galactosamine-sensitized mice. Histological estimation revealed that massive cell infiltration followed by severe injury develope d in the livers of lipopolysaccharide-treated and D-galactosamine-treated m ice unless they had been pretreated with naringin. Appearance of apoptotic cells was also found to decrease by treatment with naringin. Increases in s erum levels of aspartate aminotransferase, alanine aminotransferase and cre atine kinase, responsible for lipopolysaccharide-induced liver injury, bloc ked by naringin administration and the levels were nearly to the normal lev el. These results indicate that action of naringin is mediated through supp ression of lipopolysaccharide-induced TNF production. (C) 1999 Elsevier Sci ence B.V. All rights reserved.