title: Gadolinium chloride, a Kupffer cell inhibitor, attenuates hepatic injury in a rat model of chronic cholestasis.
abstract: The aim of the current study was to elucidate the effect of Kupffer cells inhibition on hepatic injury induced by chronic cholestasis. Sprague-Dawley rats underwent bile duct ligation (BDL) or sham operation and were treated with either saline solution or gadolinium chloride (GdCl(3), a specific Kupffer cell inhibitor, 20 mg/kg i.p. daily). Serum and liver samples were collected after 28 days. Direct and total bilirubin concentrations and serum enzyme activities of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase (GGT) increased following BDL (p < 0.01). On the contrary to bilirubin concentrations and AST activity, GdCl(3) partially prevented the elevation in ALP, ALT and GGT enzyme activities (p < 0.05). GdCl(3) alleviated lipid peroxidation (reflected by malondialdehyde [MDA] concentration) and increased the activities of antioxidant enzymes (i.e. catalase and glutathione peroxidase) in liver samples after BDL (p < 0.05). Fibrosis, ductular proliferation and portal inflammation were also scored in liver samples. Among morphological changes appeared following BDL (i.e. marked fibrosis, portal inflammation and ductular proliferation); only ductular proliferation was not alleviated by GdCl(3). Therefore, Kupffer cells inhibition has beneficial effects against the development of hepatic injury induced by chronic cholestasis.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Zandieh
authors.forename: Seyedmehedi
authors.initials: S
authors.lastname: Payabvash
authors.forename: Parvin
authors.initials: P
authors.lastname: Pasalar
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Morteza
authors.forename: Basira
authors.initials: B
authors.lastname: Zandieh
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Tavangar
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001663:Bilirubin / Q000097:blood; D002374:Catalase / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002779:Cholestasis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005355:Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005682:Gadolinium / Q000494:pharmacology / Q000627:therapeutic use*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006520:Hepatitis, Animal / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007728:Kupffer Cells / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014166:Transferases / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D008315:Malondialdehyde; D005682:Gadolinium; D002374:Catalase; D005979:Glutathione Peroxidase; D014166:Transferases; D000469:Alkaline Phosphatase; C038958:gadolinium chloride; D001663:Bilirubin