title: Anti-CD163-dexamethasone protects against apoptosis after ischemia/reperfusion injuries in the rat liver.
abstract: OBJECTIVE
  The Pringle maneuver is a way to reduce blood loss during liver surgery. However, this may result in ischemia/reperfusion injury in the development of which Kupffer cells play a central role. Corticosteroids are known to have anti-inflammatory effects. Our aim was to investigate whether a conjugate of dexamethasone and antibody against the CD163 macrophage cell surface receptor could reduce ischemia/reperfusion injury in the rat liver.
  
  
  METHODS
  Thirty-six male Wistar rats were used for the experiments. Animals were randomly divided into four groups of eight receiving anti-CD163-dexamethasone, high dose dexamethasone, low dose dexamethasone or placebo intravenously 18 h before laparotomy with subsequent 60 min of liver ischemia. After reperfusion for 24 h the animals had their liver removed. Bloods were drawn 30 min and 24 h post ischemia induction. Liver cell apoptosis and necrosis were analyzed by stereological quantification.
  
  
  RESULTS
  After 24 h' reperfusion, the fraction of cell in non-necrotic tissues exhibiting apoptotic profiles was significantly lower in the high dose dexamethasone (p = 0.03) and anti-CD163-dex (p = 0.03) groups compared with the low dose dexamethasone and placebo groups. There was no difference in necrotic cell volume between groups. After 30 min of reperfusion, levels of haptoglobin were significantly higher in the anti-CD163-dex and high dose dexamethasone groups. Alanine aminotransferase and alkaline phosphatase were significantly higher in the high dose dexamethasone group compared to controls after 24 h' reperfusion.
  
  
  CONCLUSIONS
  We show that pharmacological preconditioning with anti-CD163-dex and high dose dexamethasone reduces the number of apoptotic cells following ischemia/reperfusion injury.
authors.affiliation: Department of Surgical Gastroenterology, Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus C, Denmark.
authors.forename: Lin Nanna Okholm
authors.initials: LN
authors.lastname: Møller
authors.affiliation: Department of Surgical Gastroenterology, Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus C, Denmark.
authors.forename: Anders Riegels
authors.initials: AR
authors.lastname: Knudsen
authors.affiliation: Department of Surgical Gastroenterology, Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus C, Denmark.
authors.forename: Kasper Jarlhelt
authors.initials: KJ
authors.lastname: Andersen
authors.affiliation: Stereology & Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus C, Denmark.
authors.forename: Jens Randel
authors.initials: JR
authors.lastname: Nyengaard
authors.affiliation: Institute of Pathology, Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus C, Denmark.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hamilton-Dutoit
authors.affiliation: Department of Surgical Gastroenterology, Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus C, Denmark.
authors.forename: Elise Marie
authors.initials: EM
authors.lastname: Okholm Møller
authors.affiliation: Department of Biomedicine, Aarhus University, Ole Worms Allé 3, 8000 Aarhus C, Denmark.
authors.forename: Pia
authors.initials: P
authors.lastname: Svendsen
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus C, Denmark.
authors.forename: Holger Jon
authors.initials: HJ
authors.lastname: Møller
authors.affiliation: Department of Biomedicine, Aarhus University, Ole Worms Allé 3, 8000 Aarhus C, Denmark.
authors.forename: Søren Kragh
authors.initials: SK
authors.lastname: Moestrup
authors.affiliation: Affinicon ApS, Aabogade 15, 8200 Aarhus N, Denmark ; Institute of Molecular Medicine, University of Southern Denmark, J. B. Winsløws vej 21-25, 5000 Odense C, Denmark.
authors.forename: Jonas Heilskov
authors.initials: JH
authors.lastname: Graversen
authors.affiliation: Department of Surgical Gastroenterology, Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus C, Denmark.
authors.forename: Frank Viborg
authors.initials: FV
authors.lastname: Mortensen
keywords: ALT, alanine aminotransferase; AP, alkaline phosphatase; AST, aspartate transaminase; Anti-CD163-dex, anti-CD163-dexamethasone; BR, bilirubin; CD-163; Dexamethasone; GGT, gamma-glutamyl transferase; HDD, high-dose dexamethasone; HE, hematoxylin & eosin; Hp, haptoglobin; IL-1, interleukin 1; IL-6, interleukin 6; IRI, ischemia/reperfusion injury; Inflammatory response; Ischemia/reperfusion injury; LDD, low-dose dexamethasone; Liver; MP, methylprednisolone; NVR, necrotic volume ratio; PM, pringles maneuver; ROS, reactive oxygen species; SURS, systematic, uniform, random sampling; TNF-α, tumor necrosis factor α