title: Carbon tetrachloride-induced liver damage in asialoglycoprotein receptor-deficient mice.
abstract: The asialoglycoprotein (ASGP) receptor is an abundant hepatocyte-specific receptor involved in receptor-mediated endocytosis. This receptor's abundance and function is decreased by chronic ethanol administration prior to the appearance of pathology such as necrosis or inflammation. Hence, this study aimed to determine if ASGP receptor function is required to protect against liver injury by utilizing a knockout mouse model lacking functional ASGP receptor in the setting of carbon tetrachloride (CCl(4)) hepatotoxicity. Briefly, ASGP receptor-deficient (RD) mice and wild-type (WT) mice were injected with 1ml/kg body weight of CCl(4). In the subsequent week, mice were monitored for liver damage and pathology (aspartate transaminase (AST), alanine transaminase (ALT) and light microscopy). The consequences of CCl(4) injection were examined by measuring alpha-smooth muscle actin (alpha-SMA) deposition, contents of malondialdehyde and the percentage of apoptotic hepatocytes. After CCl(4) injection, RD mice showed increased liver pathology together with significantly increased activities of AST and ALT compared to that in WT mice. There were also significantly more apoptotic bodies, lipid peroxidation and deposition of alpha-SMA in RD mice versus WT mice following CCl(4) injection. Since these two mouse strains only differ in whether or not they have the ASGP receptor, it can be concluded that proper ASGP receptor function exerted a protective effect against CCl(4) toxicity. Thus, receptor-mediated endocytosis by the ASGP receptor could represent a novel molecular mechanism that is responsible for subsequent liver health or injury.
authors.affiliation: Department of Internal Medicine, University of Nebraska Medical Center, Omaha, 68198-2000, USA.
authors.forename: Shana R
authors.initials: SR
authors.lastname: Dalton
authors.forename: Serene M L
authors.initials: SM
authors.lastname: Lee
authors.forename: Rachel N
authors.initials: RN
authors.lastname: King
authors.forename: Amin A
authors.initials: AA
authors.lastname: Nanji
authors.forename: Kusum K
authors.initials: KK
authors.lastname: Kharbanda
authors.forename: Carol A
authors.initials: CA
authors.lastname: Casey
authors.forename: Benita L
authors.initials: BL
authors.lastname: McVicker
mesh_terms: D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000172:deficiency* / Q000235:genetics; D002251:Carbon Tetrachloride / Q000633:toxicity*; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D037263:Asialoglycoprotein Receptor; D002251:Carbon Tetrachloride