title: Glutathione treatment protects the rat liver against injury after warm ischemia and Kupffer cell activation.
abstract: OBJECTIVE
  The generation of reactive oxygen species by activated Kupffer cells (KC) may contribute to reperfusion injury of the liver during liver transplantation or resection. The aim of our present studies was to investigate (1) prevention of hepatic reperfusion injury after warm ischemia by administration of the antioxidant glutathione (GSH) and (2) whether GSH confers protection through influences on KC toxicity.
  
  
  METHODS
  Isolated perfused rat livers were subjected to 1 h of warm ischemia followed by 90 min of reperfusion without (n = 5) or with GSH or catalase (n = 4-5 each). Selective KC activation by zymosan (150 micro g/ml) in continuously perfused rat livers was used to investigate KC-related liver injury.
  
  
  RESULTS
  Postischemic infusion of 0.1, 0.5, 1.0 and 2.0 mM GSH, but not 0.05 mM GSH prevented reperfusion injury after warm ischemia as indicated by a marked reduction of sinusoidal LDH efflux by up to 83 +/- 13% (mean +/- SD; p < 0.05) and a concomitant significant improvement of postischemic bile flow by 58 +/- 27% (p < 0.05). A similar protection was conveyed by KC blockade with gadolinium chloride indicating prevention of KC-related reperfusion injury by postischemic GSH treatment. Postischemic treatment with catalase (150 U/ml) resulted in a reduction of LDH efflux by 40 +/- 9% (p < 0.05). Accordingly, catalase as well as GSH (0.1-2.0 mM) nearly completely prevented the increase in LDH efflux following selective KC activation by zymosan in continously perfused rat livers.
  
  
  CONCLUSIONS
  Postischemic administration of GSH protects the liver against reperfusion injury after warm ischemia. Detoxification of KC-derived hydrogen peroxide seem to be an important feature of the protective mechanisms.
authors.affiliation: Department of Medicine II, Klinikum Grosshadern, Ludwig Maximilian University of Munich, Germany. manfred.bilzer@t-online.de
authors.forename: Manfred
authors.initials: M
authors.lastname: Bilzer
authors.forename: Andreas
authors.initials: A
authors.lastname: Baron
authors.forename: Rolf
authors.initials: R
authors.lastname: Schauer
authors.forename: Christian
authors.initials: C
authors.lastname: Steib
authors.forename: Stefan
authors.initials: S
authors.lastname: Ebensberger
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Gerbes
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology*; D007728:Kupffer Cells / Q000378:metabolism*; D008099:Liver / Q000098:blood supply*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D015054:Zymosan / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D015054:Zymosan; D005978:Glutathione