Fundamental efforts toward the development of a therapeutic cocktail with a manifold ameliorative effect on hepatic ischemia/reperfusion injury.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
This study depicts that multifaceted pharmacological tackling of ischemia/reperfusion injury is feasible and protects rat liver tissue from warm ischemia/reperfusion injury.
Schindler
Genevieve
G
Department of General Surgery, Ruprecht-Karls-University, Heidelberg, Germany.
Kincius
Marius
M
Liang
Rui
R
Backhaus
Jürgen
J
Zorn
Markus
M
Flechtenmacher
Christa
C
Gebhard
Martha-Maria
MM
Büchler
Markus W
MW
Schemmer
Peter
P
D000409:Alanine / Q000627:therapeutic use; D000818:Animals; D001120:Arginine / Q000627:therapeutic use; D002634:Chemotaxis, Leukocyte; D004796:Clinical Enzyme Tests; D004359:Drug Therapy, Combination; D005998:Glycine / Q000627:therapeutic use; D008102:Liver Circulation; D008107:Liver Diseases / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D009336:Necrosis; D010587:Phagocytosis; D011239:Prednisolone / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D013654:Taurine / Q000627:therapeutic use; D016896:Treatment Outcome
D013654:Taurine; D001120:Arginine; D011239:Prednisolone; D000409:Alanine; D005998:Glycine