title: Hydrogen peroxide derived from hepatocytes induces sinusoidal endothelial cell apoptosis in perfused hypoxic rat liver.
abstract: OBJECTIVE
  Evidence is accumulating that hypoxic liver injury involves not only necrosis but also apoptosis. Reactive oxygen species can cause apoptosis. This study examined the hypothesis that H2O2 induces apoptosis in hypoxic rat liver.
  
  
  METHODS
  Blood-perfused rat livers were made hypoxic by reducing the perfusion flow. H2O2 was detected by both 2',7'-dichlorofluorescein fluoroimaging and cerium electron-microscopic methods. To evaluate the apoptosis, the liver was stained with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) method. To further investigate the involvement of H2O2 in hypoxia-induced liver cell apoptosis, small pieces of liver in the cultured media were exposed to 0.5 mmol/L of reagent H2O2 and stained with the TUNEL method.
  
  
  RESULTS
  In the hypoxic liver, H2O2 was produced predominantly by hepatocytes, and the number of apoptotic nonparenchymal cells was significantly increased, particularly in the midzone. All the apoptotic cells were positively stained with monoclonal antibody against the hepatic sinusoidal endothelial cells (SECs). In incubated liver pieces, reagent H2O2 induced apoptosis selectively in SECs.
  
  
  CONCLUSIONS
  Low-flow hypoxia induces H2O2 production in hepatocytes, and this H2O2 induces apoptosis selectively in SECs in the rat liver.
authors.affiliation: Second Department of Surgery, Akita University School of Medicine, Japan. motoyama@med.akita-u.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Motoyama
authors.forename: Y
authors.initials: Y
authors.lastname: Minamiya
authors.forename: S
authors.initials: S
authors.lastname: Saito
authors.forename: R
authors.initials: R
authors.lastname: Saito
authors.forename: I
authors.initials: I
authors.lastname: Matsuzaki
authors.forename: S
authors.initials: S
authors.lastname: Abo
authors.forename: H
authors.initials: H
authors.lastname: Inaba
authors.forename: K
authors.initials: K
authors.lastname: Enomoto
authors.forename: M
authors.initials: M
authors.lastname: Kitamura
mesh_terms: D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia; D004727:Endothelium / Q000473:pathology / Q000503:physiopathology; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008099:Liver / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006861:Hydrogen Peroxide