title: Protective effect of genistein on lipopolysaccharide/D-galactosamine- induced hepatic failure in mice.
abstract: This study examined the effect of genistein from Hydrocotyle sibthorpioides on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute hepatic failure. Compared to the model control, genistein treatment significantly protected against LPS/D-GalN-induced liver injury, as evidenced by the decrease in serum alanine and aspartate aminotransferases activities and the attenuation of histopathological changes. Furthermore, genistein alleviated the pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO)/inducible nitric oxide synthase (iNOS) by inhibiting nuclear factor-κB (NF- κB) activity. Genistein attenuated the elevated level of caspases-3, while augmented the expression of Bcl-2. In addition, LPS/D-GalN induced significant increase of heme oxygenase (HO), carbon monoxide and bilirubin levels and these alterations were augmented by genistein treatment. In conclusion, the protective effect of genistein on LPS/D-GalN-induced liver damage was mainly due to its ability to block NF-κB signaling pathway for anti-inflammation response, attenuate hepatocellular apoptosis and increase HO level. These findings suggest that genistein can be considered as a potential agent for preventing acute hepatic failure.
authors.forename: Xing
authors.initials: X
authors.lastname: Lin
authors.forename: Shijun
authors.initials: S
authors.lastname: Zhang
authors.forename: Renbin
authors.initials: R
authors.lastname: Huang
authors.forename: Ling
authors.initials: L
authors.lastname: Wei
authors.forename: Chunhong
authors.initials: C
authors.lastname: Liang
authors.forename: Yongxing
authors.initials: Y
authors.lastname: Chen
authors.forename: Shujuan
authors.initials: S
authors.lastname: Lv
authors.forename: Shuang
authors.initials: S
authors.lastname: Liang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wu
authors.forename: Quanfang
authors.initials: Q
authors.lastname: Huang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002248:Carbon Monoxide / Q000032:analysis / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D005688:Galactosamine; D019833:Genistein / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides; D017093:Liver Failure / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D020011:Protective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D005688:Galactosamine; D002248:Carbon Monoxide; D019833:Genistein; D052247:Nitric Oxide Synthase Type II; D006419:Heme Oxygenase (Decyclizing); D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053148:Caspase 3; D001663:Bilirubin