73 Therapeutic Effects of Melittin Against Acetaminophen-Induced Liver Injury in Mice

Abstract

Study Objective: An overdose of acetaminophen (APAP) frequently causes severe liver injury, but the treatment options remain limited. Melittin is a bioactive peptide derived from bee venom and possesses anti-oxidative, anti- apoptotic, and anti-inflammatory properties. Emerging evidence suggests that this peptide exerts beneficial effects on several inflammatory disorders. However, whether melittin has a protective effect on APAP toxicity remains undetermined. The purpose of the current study was to investigate the effect of melittin on APAP-induced hepatotoxicity.Methods: Melittin was intraperitoneally administered at a dose of 0.01 mg/kg to mice 1 hour after APAP injection (400 mg/kg).Results: Administration of melittin after APAP injection reduced serum aspartate aminotransferase and alanine aminotransferase levels and alleviated histological alterations in APAP-injected mice. Melittin inhibited lipid peroxidation and DNA oxidation with restoration of glutathione content and upregulation of antioxidant enzymes. Melittin also attenuated hepatocyte apoptosis with inhibition of caspase-3 activation. In addition, serum and hepatic levels of cytokines were reduced by melittin. This effect was associated with inhibition of nuclear factor-κB activation. Furthermore, melittin attenuated infiltration of neutrophils and macrophages into the liver.Conclusion: Altogether, these data suggest that melittin might be served as a treatment agent for APAP-induced hepatotoxicity.View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)No, authors do not have interests to disclose Study Objective: An overdose of acetaminophen (APAP) frequently causes severe liver injury, but the treatment options remain limited. Melittin is a bioactive peptide derived from bee venom and possesses anti-oxidative, anti- apoptotic, and anti-inflammatory properties. Emerging evidence suggests that this peptide exerts beneficial effects on several inflammatory disorders. However, whether melittin has a protective effect on APAP toxicity remains undetermined. The purpose of the current study was to investigate the effect of melittin on APAP-induced hepatotoxicity. Methods: Melittin was intraperitoneally administered at a dose of 0.01 mg/kg to mice 1 hour after APAP injection (400 mg/kg). Results: Administration of melittin after APAP injection reduced serum aspartate aminotransferase and alanine aminotransferase levels and alleviated histological alterations in APAP-injected mice. Melittin inhibited lipid peroxidation and DNA oxidation with restoration of glutathione content and upregulation of antioxidant enzymes. Melittin also attenuated hepatocyte apoptosis with inhibition of caspase-3 activation. In addition, serum and hepatic levels of cytokines were reduced by melittin. This effect was associated with inhibition of nuclear factor-κB activation. Furthermore, melittin attenuated infiltration of neutrophils and macrophages into the liver. Conclusion: Altogether, these data suggest that melittin might be served as a treatment agent for APAP-induced hepatotoxicity. No, authors do not have interests to disclose