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

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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.

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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

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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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Authors and Affiliations

  1. Department of Pathology, College of Medicine, Catholic University of Daegu, 3056-6, Daemyung 4-Dong, Nam-gu, Daegu, 705-718, Republic of Korea

    Ji-Hyun Park, Kyung-Hyun Kim, Woo-Ram Lee & Kwan-Kyu Park

  2. Department of Agricultural Biology, National Institute of Agricultural Science and Technology, Suwon, 441-100, Republic of Korea

    Sang-Mi Han

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Correspondence to Kwan-Kyu Park.

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Park, JH., Kim, KH., Lee, WR. et al. Protective effect of melittin on inflammation and apoptosis in acute liver failure. Apoptosis 17, 61–69 (2012). https://doi.org/10.1007/s10495-011-0659-0

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