Background. Cholestatic liver injury is a leading cause of chronic liver diseases involved with oxidative stress changes and inflammation; thus, antioxidant and anti-inflammation compound-rich guava may play a pivotal role in protecting against the cholestatic liver damages. Our aims for this study are to determine whether guava pulp (GP) has protective effects on cholestatic liver injury-induced mouse model and on interleukin-6 (IL-6) mediated proliferation of QBC939 cholangiocarcinoma cell line. Methods. Mice were induced to cholestatic liver damage by left and median bile duct ligation (LMBDL) surgery and then treated with GP. Plasma and liver samples were collected for biochemical and pathological assays. 5-Bromo-2′-deoxyuridine (BrdU) assay and Western blots were used to detect proliferation and gene expression in QBC939 cells, respectively. Results. Compared with LMBDL only group, in GP-treated mice, the levels of alanine aminotransferase (ALT) and bilirubin decreased, biliary epithelial cell proliferation and liver fibrogenesis were suppressed, Src/MEK/ERK1/2/c-Myc pathway and expressions of transforming growth factor β1(TGF-β1), tissue inhibitor of metalloproteinases TIMP), and procollagen 1α1(COL1α1) were downregulated significantly. Moreover, the GP extract reduced IL-6-enhanced QBC939 cell proliferation, p-ERK, and c-Myc expression as well. Conclusions. GP may provide a new perspective for the treatment of cholestatic liver injury. 1. Introduction Cholestasis, which is caused by acute or chronic interruption in bile export, is a well-known risk factor for complications after liver surgery [1]. Also, it is an important cause of liver damages. Posthepatic (obstructive) cholestasis is characterized by portal tract expansion, leukocyte infiltration, bile duct and septal proliferation, liver fibrosis, and eventually cirrhosis in human [2]. Patients with cholestasis, such as extrahepatic bile duct cancer, are at a greater risk for postoperative liver failure, sepsis, and death [3]. Therefore, intensive researches are required to find effective therapeutic agents for cholestatic liver injury. Common bile duct ligation (CBDL) is a well known cholestatic model of extrahepatic biliary obstruction [4]. However, CBDL generally develops hepatic, intraperitoneal, and pulmonary abscesses, and even sepsis which leads to the early mortality of CBDL animals. To establish a model that is closer to the human situation, we established a new, reproducible model of chronic cholestatic liver injury [5]. In order to study chronic cholestatic liver injuries better, we
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