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Apoptosis

, Volume 17, Issue 1, pp 61–69 | Cite as

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

  • Ji-Hyun Park
  • Kyung-Hyun Kim
  • Woo-Ram Lee
  • Sang-Mi Han
  • Kwan-Kyu ParkEmail author
Original Paper

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.

Keywords

Apoptosis Inflammatory cytokine Melittin Acute liver failure TNF-α NF-κB 

Abbreviations

TNF-α

Tumor necrosis factor

GalN

d-Galactosamine

LPS

Lipopolysaccharide

i.p.

Intraperitoneal

IL-1β

Interleukin

NF-κB

Nuclear factor-kappa B

ALT

Alanine aminotransferase

VSMC

Vascular smooth muscle cell

MAPK

Mitogen-activated protein kinases

EMSA

Electrophoretic mobility shift analysis

IHC

Immunohistochemistry

TUNEL

Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling

Notes

Acknowledgments

This work was supported by a grant (PJ0081302011) from the BioGreen 21 Program, Rural Development Administration, and Republic of Korea.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Ji-Hyun Park
    • 1
  • Kyung-Hyun Kim
    • 1
  • Woo-Ram Lee
    • 1
  • Sang-Mi Han
    • 2
  • Kwan-Kyu Park
    • 1
    Email author
  1. 1.Department of PathologyCollege of Medicine, Catholic University of DaeguDaeguRepublic of Korea
  2. 2.Department of Agricultural BiologyNational Institute of Agricultural Science and TechnologySuwonRepublic of Korea

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