Suppression of lipopolysaccharide-induced tumor necrosis factor-release and liver injury in mice by naringin.
Suppressive effects of naringin on lipopolysaccharide-induced tumor necrosis factor (TNF) release followed by liver injury were investigated. Intraperitoneal (i.p.) treatment with naringin prior to an intravenous (i.v.) challenge 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 lipopolysaccharide challenge resulted in complete protection from lipopolysaccharide lethality in D-galactosamine-sensitized mice. Histological estimation revealed that massive cell infiltration followed by severe injury developed in the livers of lipopolysaccharide-treated and D-galactosamine-treated mice unless they had been pretreated with naringin. Appearance of apoptotic cells was also found to decrease by treatment with naringin. Increases in serum levels of aspartate aminotransferase, alanine aminotransferase and creatine kinase, responsible for lipopolysaccharide-induced liver injury, blocked by naringin administration and the levels were nearly to the normal level. These results indicate that action of naringin is mediated through suppression of lipopolysaccharide-induced TNF production.
Kawaguchi
K
K
Medicinal Plant Garden, School of Pharmaceutical Sciences, Kitasato University, Sagamihara, Japan.
Kikuchi
S
S
Hasegawa
H
H
Maruyama
H
H
Morita
H
H
Kumazawa
Y
Y
D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D003402:Creatine Kinase / Q000097:blood / Q000187:drug effects; D005260:Female; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D005688:Galactosamine / Q000276:immunology; D020287:In Situ Nick-End Labeling; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D008107:Liver Diseases / Q000401:mortality / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000378:metabolism
D000975:Antioxidants; D044950:Flavanones; D005419:Flavonoids; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003402:Creatine Kinase; C005274:naringin