Protective effects of melittin on tumor necrosis factor-α
induced hepatic damage through suppression of apoptotic pathway and nuclear
factor-kappa B activation
Exp Biol Med (Maywood), 2014 May 28
Melittin, a major polypeptide in honeybee venom, have been
used to treat inflammatory disease. Various studies have demonstrated the
anti-bacterial, anti-viral, anti-inflammatory and anticancer effects of bee
venom and melittin. However, the precise mechanism of melittin in liver disease
is not yet known.
Apoptosis contributes to liver inflammation and fibrosis.
Knowledge of the apoptotic mechanisms is important to develop new and effective
therapies for treatment of cirrhosis. In the present study, we investigated the
anti-apoptotic effect of melittin on tumor necrosis factor (TNF)-α/actinomycin
(Act) D-induced apoptosis in hepatocytes. Our results show significant
protection from DNA damage by melittin treatment compared with corresponding
TNF-α/Act D-treated hepatocytes without melittin. Melittin inhibited TNF-α/Act
D-induced activation of the caspase, bcl-2 family of proteins and poly
ADP-ribose polymerase (PARP)-1.
Our results also indicate that melittin
decreased nuclear factor-kappa B (NF-κB) by degradation of phosphorylation of
IκB kinase (p-IKK) and NF-κB DNA binding activity in TNF-α/Act D-treated
hepatocytes. These results suggest that melittin possesses a potent suppressive
effect on apoptotic responses in TNF-α/Act D-treated hepatocytes via the NF-κB
pathway.
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