title: Fundamental efforts toward the development of a therapeutic cocktail with a manifold ameliorative effect on hepatic ischemia/reperfusion injury.
abstract: 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.
authors.affiliation: Department of General Surgery, Ruprecht-Karls-University, Heidelberg, Germany.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Schindler
authors.forename: Marius
authors.initials: M
authors.lastname: Kincius
authors.forename: Rui
authors.initials: R
authors.lastname: Liang
authors.forename: Jürgen
authors.initials: J
authors.lastname: Backhaus
authors.forename: Markus
authors.initials: M
authors.lastname: Zorn
authors.forename: Christa
authors.initials: C
authors.lastname: Flechtenmacher
authors.forename: Martha-Maria
authors.initials: MM
authors.lastname: Gebhard
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.forename: Peter
authors.initials: P
authors.lastname: Schemmer
mesh_terms: 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
chemical_list: D013654:Taurine; D001120:Arginine; D011239:Prednisolone; D000409:Alanine; D005998:Glycine