Effects of Melittin Treatment in Cholangitis and Biliary Fibrosis in a Model of Xenobiotic-Induced Cholestasis in Mice

Abstract

Cholangiopathy is a chronic immune-mediated disease of the liver, which is characterized by cholangitis, ductular reaction and biliary-type hepatic fibrosis. There is no proven medical therapy that changes the course of the disease. In previous studies, melittin was known for attenuation of hepatic injury, inflammation and hepatic fibrosis. This study investigated whether melittin provides inhibition on cholangitis and biliary fibrosis in vivo. Feeding 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) to mice is a well-established animal model to study cholangitis and biliary fibrosis. To investigate the effects of melittin on cholangiopathy, mice were fed with a 0.1% DDC-containing diet with or without melittin treatment for four weeks. Liver morphology, serum markers of liver injury, cholestasis markers for inflammation of liver, the degree of ductular reaction and the degree of liver fibrosis were compared between with or without melittin treatment DDC-fed mice. DDC feeding led to increased serum markers of hepatic injury, ductular reaction, induction of pro-inflammatory cytokines and biliary fibrosis. Interestingly, melittin treatment attenuated hepatic function markers, ductular reaction, the reactive phenotype of cholangiocytes and cholangitis and biliary fibrosis. Our data suggest that melittin treatment can be protective against chronic cholestatic disease in DDC-fed mice. Further studies on the anti-inflammatory capacity of melittin are warranted for targeted therapy in cholangiopathy.

The Protective Effect of Melittin on Renal Fibrosis in an Animal Model of Unilateral Ureteral Obstruction

“…Further, a recent study indicated that melittin prevents the DDC diet-induced expression levels of inflammatory cytokines and fibrosis-related genes. This study demonstrated the protective effects of melittin on DDC-induced biliary fibrosis in vivo [30]. On the basis of this information, our current study investigated the question of whether melittin could affect inflammation and fibrosis reaction after renal injury.…”

Apamin suppresses biliary fibrosis and activation of hepatic stellate cells

“…For induction of liver injury, 8-week-old C57BL/6 male mice (20–25 g; Samtako, Osan, Korea) were selected. Male C57BL/6 mice were fed a control diet or a DDC supplemented diet (0.1%) for 4 weeks to induce advanced biliary fibrosis as previously described ( 15 ). All animal protocols were approved by the Institutional Animal Care and Use Committee of Catholic University of Daegu (Daegu, Korea).…”

Anti-Inflammatory Applications of Melittin, a Major Component of Bee Venom: Detailed Mechanism of Action and Adverse Effects

“…Recently, they showed that administration of melittin attenuated inflammation and fibrosis of the bile duct. Their experimental results suggest that melittin may have therapeutic applications in chronic liver injury [52]. Figure 1 summarizes the major mechanisms of the anti-inflammatory action of melittin.…”