Document Detail

Lipid peroxidation as molecular mechanism of liver cell injury during reperfusion after ischemia.
MedLine Citation:
PMID:  8070679     Owner:  NLM     Status:  MEDLINE    
The pathophysiological importance of reactive oxygen species has been extensively documented in the pathogenesis of hepatic ischemia-reperfusion injury. Kupffer cells and neutrophils were identified as the dominant sources of the postischemic oxidant stress. To test the hypothesis that a direct free radical-mediated injury mechanism (lipid peroxidation; LPO) may be involved in the pathogenesis, highly sensitive and specific parameters of LPO, i.e., hydroxy-eicosatetraenoic acids (HETES), and F2-isoprostanes, were determined by gas chromatographic-mass spectrometric analysis in liver tissue and plasma during 45 min of hepatic ischemia and up to 24 h of reperfusion. A significant 60-250% increase of F2-isoprostane levels in plasma was found at all times during reperfusion; the HETE content increased only significantly at 1 h of reperfusion and in severely necrotic liver tissue at 24 h with increases between 90-320%. On the other hand, in a model of LPO-induced liver injury (infusion of 0.8 mumol tert-butylhydroperoxide/min/g liver), the hepatic HETE content increased two to fourfold over baseline values at 45 min, i.e., before liver injury. A further increase to 12- to 30-fold of baseline was observed during moderate liver injury. Based on these quantitative comparisons of LPO and liver injury, it seems highly unlikely that LPO is the primary mechanism of parenchymal cell injury during reperfusion, although it cannot be excluded that LPO may be important as a damaging mechanism in a limited compartment of the liver, e.g., endothelial cells, close to the sources of reactive oxygen, e.g., Kupffer cells and neutrophils.
W R Mathews; D M Guido; M A Fisher; H Jaeschke
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Free radical biology & medicine     Volume:  16     ISSN:  0891-5849     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  1994 Jun 
Date Detail:
Created Date:  1994-09-26     Completed Date:  1994-09-26     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  763-70     Citation Subset:  IM    
Upjohn Laboratories, Upjohn Company, Kalamazoo, MI 49001.
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MeSH Terms
Alanine Transaminase / blood
Analysis of Variance
Dinoprost / blood
Gas Chromatography-Mass Spectrometry
Glutathione / analogs & derivatives,  blood
Glutathione Disulfide
Ischemia / blood,  metabolism*
Lipid Peroxidation*
Liver / blood supply*
Peroxides / pharmacology
Rats, Inbred F344
Reactive Oxygen Species / pharmacology
Time Factors
Grant Support
Reg. No./Substance:
0/Peroxides; 0/Reactive Oxygen Species; 27025-41-8/Glutathione Disulfide; 551-11-1/Dinoprost; 70-18-8/Glutathione; 75-91-2/tert-Butylhydroperoxide; EC Transaminase

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