title: Carvedilol Attenuates the Progression of Hepatic Fibrosis Induced by Bile Duct Ligation.
abstract: Background.The sympathetic nervous system (SNS) is responsible for hepatic stellate cells (HSCs) activation and the accumulation of collagen that occurs in hepatic fibrogenesis. Carvedilol has been widely used for the complication of hepatic cirrhosis in the clinic. Furthermore, it has powerful antioxidant properties. We assessed the potential antifibrotic effects of carvedilol and the underlying mechanisms that may further enhance its clinical benefits.Methods.Using a bile duct ligation rat model of hepatic fibrosis, we studied the effects of carvedilol on the fibrosis, collagen deposition, and oxidative stress based on histology, immunohistochemistry, western blot, and RT-PCR analyses.Results.Carvedilol attenuated liver fibrosis, as evidenced by reduced hydroxyproline content and the accumulation of collagen, downregulated TIMP-1 and TIMP-2, and upregulated MMP-13. MMP-2 was an exception, which was decreased after carvedilol treatment for 2 weeks and upregulated after carvedilol treatment for 4 weeks. Carvedilol reduced the activation of HSCs, decreased the induction of collagen, transforming growth factor-β1, and MDA content, and strengthened the SOD activity. The antifibrotic effects were augmented as dosages increased.Conclusions.The study indicates that carvedilol attenuated hepatic fibrosis in a dose-dependent manner. It can decrease collagen accumulation and HSCs activation by the amelioration of oxidative stress.
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, China; Department of Gastroenterology, Xingtai People's Hospital, Xingtai, Hebei 054000, China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, China; Department of Fever Related Disease, The PLA General Hospital, Beijing 100853, China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, China.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, China; Department of Gastroenterology, Xingtai People's Hospital, Xingtai, Hebei 054000, China.
authors.forename: Shurui
authors.initials: S
authors.lastname: Xie
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, China.
authors.forename: Fengrong
authors.initials: F
authors.lastname: Yin
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Huo
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, China.
authors.forename: Xiaolan
authors.identifier: 0000-0002-7047-3634
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000187:drug effects* / Q000503:physiopathology; D002227:Carbazoles / Q000008:administration & dosage*; D000077261:Carvedilol; D003094:Collagen / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D008026:Ligation / Q000009:adverse effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects; D011412:Propanolamines / Q000008:administration & dosage*; D051381:Rats; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis
chemical_list: D002227:Carbazoles; D011412:Propanolamines; D019715:Tissue Inhibitor of Metalloproteinase-1; D000077261:Carvedilol; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen; D053509:Matrix Metalloproteinase 13; D006909:Hydroxyproline