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: Ji-Hyun Park, Kyung-Hyun Kim, Woo-Ram Lee, Sang-Mi Han, Kwan-Kyu Park
• Journal: Apoptosis : an international journal on programmed cell death (Apoptosis) Vol. 17 Issue 1 Pg. 61-9 (Jan 2012) ISSN: 1573-675X [Electronic] Netherlands
• PMID: 21928088 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Protective Agents
• Melitten

Topics

• Animals
• Anti-Inflammatory Agents (administration & dosage)
• Apoptosis (drug effects)
• Cytokines (immunology)
• Disease Models, Animal
• Hepatocytes (cytology, drug effects)
• Humans
• Liver Failure, Acute (drug therapy, immunology, physiopathology)
• Male
• Melitten (administration & dosage)
• Mice
• Mice, Inbred C57BL
• Protective Agents (administration & dosage)