title: Mangafodipir protects against hepatic ischemia-reperfusion injury in mice.
abstract: OBJECTIVE
  Mangafodipir is a contrast agent used in magnetic resonance imaging that concentrates in the liver and displays pleiotropic antioxidant properties. Since reactive oxygen species are involved in ischemia-reperfusion damages, we hypothesized that the use of mangafodipir could prevent liver lesions in a mouse model of hepatic ischemia reperfusion injury. Mangafodipir (MnDPDP) was compared to ischemic preconditioning and intermittent inflow occlusion for the prevention of hepatic ischemia-reperfusion injury in the mouse.
  
  
  METHODS
  Mice were subjected to 70% hepatic ischemia (continuous ischemia) for 90 min. Thirty minutes before the ischemic period, either mangafodipir (10 mg/kg) or saline was injected intraperitoneally. Those experimental groups were compared with one group of mice preconditioned by 10 minutes' ischemia followed by 15 minutes' reperfusion, and one group with intermittent inflow occlusion. Hepatic ischemia-reperfusion injury was evaluated by measurement of serum levels of aspartate aminotransferase (ASAT) activity, histologic analysis of the livers, and determination of hepatocyte apoptosis (cytochrome c release, caspase 3 activity). The effect of mangafodipir on the survival rate of mice was studied in a model of total hepatic ischemia.
  
  
  RESULTS
  Mangafodipir prevented experimental hepatic ischemia-reperfusion injuries in the mouse as indicated by a reduction in serum ASAT activity (P<0.01), in liver tissue damages, in markers of apoptosis (P<0.01), and by higher rates of survival in treated than in untreated animals (P<0.001). The level of protection by mangafodipir was similar to that observed following intermittent inflow occlusion and higher than after ischemic preconditioning.
  
  
  CONCLUSIONS
  Mangafodipir is a potential new preventive treatment for hepatic ischemia-reperfusion injury.
authors.affiliation: Laboratoire d'Immunologie, EA1833 Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, AP-HP, Hôpital Cochin, Paris, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Coriat
authors.forename: Mahaut
authors.initials: M
authors.lastname: Leconte
authors.forename: Niloufar
authors.initials: N
authors.lastname: Kavian
authors.forename: Sassia
authors.initials: S
authors.lastname: Bedda
authors.forename: Carole
authors.initials: C
authors.lastname: Nicco
authors.forename: Christiane
authors.initials: C
authors.lastname: Chereau
authors.forename: Claire
authors.initials: C
authors.lastname: Goulvestre
authors.forename: Bernard
authors.initials: B
authors.lastname: Weill
authors.forename: Alexis
authors.initials: A
authors.lastname: Laurent
authors.forename: Frédéric
authors.initials: F
authors.lastname: Batteux
mesh_terms: D000818:Animals; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005978:Glutathione / Q000378:metabolism; D019194:Ischemic Preconditioning; D015227:Lipid Peroxidation; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D015996:Survival Rate
chemical_list: D017382:Reactive Oxygen Species; D011732:Pyridoxal Phosphate; D004492:Edetic Acid; D001219:Aspartate Aminotransferases; D005978:Glutathione; C060076:N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid
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