title: Protective effect of melittin on inflammation and apoptosis in acute liver failure.
abstract: Acute hepatic failure remains an extremely poor prognosis and still results in high mortality. Therefore, better treatment is urgently needed. Melittin, a major component of bee venom, is known to inhibit inflammatory reactions induced by lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-α in various cell types. However, there is no evidence of the anti-inflammatory and anti-apoptotic effect of melittin on liver cells. In the present study, we investigated the effects of melittin on D: -galactosamine (GalN)/lipopolysaccharide (LPS)-induced acute hepatic failure. Acute liver injury was induced with GalN/LPS to determine in vivo efficacy of melittin. Mice were randomly divided into four groups: sterile saline treated group (NC), melittin only treated group (NM), GalN/LPS-treated group (GalN/LPS), and GalN/LPS treated with melittin group (M+GalN/LPS). Mice were given intraperitoneal GalN/LPS with or without melittin treatment. Liver injury was assessed biochemically and histologically. Inflammatory cytokines in the serum, apoptosis of hepatocytes, and cleavage of caspase-3 in the liver were determined. The expression of TNF-α and interleukin (IL)-1β were increased in the GalN/LPS group. However, treatment of melittin attenuated the increase of inflammatory cytokines. The M+GalN/LPS group showed significantly fewer apoptotic cells compared to the GalN/LPS group. Melittin significantly inhibited the expression of caspase and bax protein levels as well as cytochrome c release in vivo. In addition, melittin prevented the activation of the transcription factor nuclear factor-kappa B (NF-κB) induced by GalN/LPS. These results clearly indicate that melittin provided protection against GalN/LPS-induced acute hepatic failure through the inhibition of inflammatory cytokines and apoptosis.
authors.affiliation: Department of Pathology, College of Medicine, Catholic University of Daegu, Daemyung Nam-gu, Daegu, Republic of Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Kyung-Hyun
authors.initials: KH
authors.lastname: Kim
authors.forename: Woo-Ram
authors.initials: WR
authors.lastname: Lee
authors.forename: Sang-Mi
authors.initials: SM
authors.lastname: Han
authors.forename: Kwan-Kyu
authors.initials: KK
authors.lastname: Park
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D006801:Humans; D017114:Liver Failure, Acute / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D008555:Melitten / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D020011:Protective Agents / Q000008:administration & dosage*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D020011:Protective Agents; D008555:Melitten