Protective effect of melittin on inflammation and apoptosis in acute liver failure

被引:78
作者
Park, Ji-Hyun [1 ]
Kim, Kyung-Hyun [1 ]
Lee, Woo-Ram [1 ]
Han, Sang-Mi [2 ]
Park, Kwan-Kyu [1 ]
机构
[1] Catholic Univ Daegu, Coll Med, Dept Pathol, Taegu 705718, South Korea
[2] Natl Inst Agr Sci & Technol, Dept Agr Biol, Suwon 441100, South Korea
关键词
Apoptosis; Inflammatory cytokine; Melittin; Acute liver failure; TNF-alpha; NF-kappa B; TUMOR-NECROSIS-FACTOR; FULMINANT HEPATIC-FAILURE; NF-KAPPA-B; D-GALACTOSAMINE; BEE VENOM; MEDIATOR GENERATION; INHIBITS APOPTOSIS; MOUSE-LIVER; LIPOPOLYSACCHARIDE; SUPPRESSION;
D O I
10.1007/s10495-011-0659-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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)-alpha in various cell types. However, there is no evidence of the anti-inflammatory and antiapoptotic 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-alpha and interleukin (IL)-1 beta 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-kappa B) 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.
引用
收藏
页码:61 / 69
页数:9
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