Protective effect and mechanism of zerumbone on severe acute pancreatitis associated liver injury in rats

Abstract

Objective This article was designed to identify the effect of zerumbone on severe acute pancreatitis associated liver injury, and to investigate the possible mechanism. It could be evidence on protection the liver injury in severe acute pancreatitis. Methods Fifty-six male Wistar rats, were randomly divided into four groups:SO group(SO group)(n= 8), Severe acute pancreatitis group(SAP group)(n= 32), Zerumbone pretreatment group(ZER group)(n= 8), Zerumbone drug control group(ZER- CON group)(n= 8). Severe acute pancreatitis group(SAP group) was divided into four time points of 1, 3, 6 and 12 h(n=8 each time point). The serum, pancreas and liver tissue were preserved.We measured serum amylase(AMY),alanine transaminase(ALT), aspartate Aminotransferase(AST), phospholipase A2(PLA 2) and pathological examination of pancreas and liver.The expression of nuclear factor- kappa B(NF-κB) p65 in liver tissue was evaluated by immunohistochemistry assay.Fresh nuclear protein of liver tissue was studied using electrophoretic mobility shift assay(EMSA).Interleukin- 1βin cytoplasm was evaluated by western blotting. Results The levels of serum AMY, ALT, AST, phospholipase and pathological examination of pancreas and liver between in SAP group were higher than in ZER-CON and in SO group. However, those in ZER group were significantly lower than in SAP group(P< 0.05).[AMY(U/L) SO:1 485.6±130.5, SAP 1 h:2 865.5±536.9, SAP 3 h:4 858.0±707.3, SAP 6 h:5 702.3± 885.2, SAP 12 h: 7 072.6±868.2, ZER: 4 367.3±811.4, ZER- CON: 1 833.4±216.9], [PLA 2(nmol/min·ml)SO:493.6±86.1, SAP 1 h:522.5±102.3, SAP 3 h:992.3±97.8, SAP 6 h:1144.7±94.4, SAP 12 h: 825.9±87.8, ZER: 653.5±92.3, ZER- CON: 552.4±86.2], [ALT(U/L)SO:87.3±8.5, SAP 1 h:92.7±10.4, SAP 3 h:166.9±21.7, SAP 6 h:188.3± 26.6, SAP 12 h:267.4±30.4, ZER: 179.4±27.9, ZER- CON: 96.6±15.0],[AST(U/L) SO:103.5±11.7, SAP 1 h:230.8±48.4, SAP 3 h:381.0±76.0, SAP 6 h:510.7±84.3, SAP 12 h:484.1±74.5, ZER: 317.1±66.2, ZER- CON: 120.3±35.1],[(Pancreatic pathologic score)SO:0.40±0.39, SAP 1 h: 3.45±0.93, SAP 3 h: 6.70±1.40, SAP 6 h: 9.35±1.68, SAP 12 h:10.85±1.89, ZER:6.96±1.21, ZER- CON:0.52±0.15].In the SAP group, the NF -κB p65 and IL- 1 expression were higher than in ZER- CON and in SO group.After administration of ZER, all of the expression was decreased(P< 0.05). Conclusion Treatment of zerumbone on rat inhibited NF-κB activation in liver tissue, and then down regulated the expression of IL-1β. It suggested that zerumbone attenuated the liver injury in pancreatitis. Key words: Zerumbone; Acute pancreatitis; Liver injury; Nuclear factor kappa B