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Schindler, G; Kincius, M; Liang, R; Backhaus, J; Zorn, M; Flechtenmacher, C; Gebhard, MM; Büchler, MW; Schemmer, P.
Fundamental efforts toward the development of a therapeutic cocktail with a manifold ameliorative effect on hepatic ischemia/reperfusion injury.
Microcirculation. 2009; 16(7):593-602
Doi: 10.1080/10739680903110779
Web of Science
PubMed
FullText
FullText_MUG
- Leading authors Med Uni Graz
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Schemmer Peter
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- Abstract:
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Ischemia/reperfusion injury is mediated by various mechanisms. The present study was designed to evaluate the effect of a multiple pharmacological approach toward ischemia/reperfusion injury reduction.
The left liver lobe of Sprague-Dawley rats underwent normothermic ischemia for 90 minutes after a cocktail (glycine, taurine, alanine, arginine, and prednisolon) intravenous administration. Controls received normal saline. Liver injury (transaminases, histology) and cellular activation [Kupffer cell phagocytosis, production of tumor necrosis factor-alpha (TNFalpha), and prostaglandin E-2 (PGE(2))], as well as microcirculation and leukocyte-endothelial interaction (in vivo microscopy), were assessed.
Whereas in controls a substantial increase of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase to 2,341+/-477, 1,442+/-262, and 1,973+/-73 U/L, respectively, was measured eight hours after reperfusion, the cocktail significantly reduced the increase of enzymes by 33-80% (P<0.05). Further, necrosis, index of liver damage, and index of leukocyte infiltration significantly decreased after the cocktail (P<0.05). Moreover, the cocktail improved acinar and sinusoidal perfusion, while the sinusoidal diameters, leukocyte-endothelial interaction, Kupffer cell phagocytic activity, and TNFalpha/PGE(2) serum levels were significantly reduced, the latter by 86% and to 1.64-fold, respectively.
This study depicts that multifaceted pharmacological tackling of ischemia/reperfusion injury is feasible and protects rat liver tissue from warm ischemia/reperfusion injury.
- Find related publications in this database (using NLM MeSH Indexing)
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Alanine - therapeutic use
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Animals -
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Arginine - therapeutic use
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Chemotaxis, Leukocyte -
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Clinical Enzyme Tests -
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Drug Therapy, Combination -
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Glycine - therapeutic use
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Liver Circulation -
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Liver Diseases - drug therapy
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Liver Diseases - enzymology
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Liver Diseases - pathology
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Necrosis -
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Phagocytosis -
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Prednisolone - therapeutic use
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Rats -
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Rats, Sprague-Dawley -
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Reperfusion Injury - drug therapy
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Taurine - therapeutic use
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Treatment Outcome -
- Find related publications in this database (Keywords)
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ischemia
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reperfusion injury
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liver
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microcirculation
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cocktail
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glycine
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taurine
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arginine
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alanine
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prednisolon