Glutathione treatment protects the rat liver against injury after warm ischemia and Kupffer cell activation

Background/Aim: 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 mug/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. Conclusion:
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. Copyright (C) 2002 S. Karger AG, Basel.