title: L-carnitine ameliorates L-asparaginase-induced acute liver toxicity in steatotic rat livers.
abstract: BACKGROUND
  Chemotherapy with L-asparaginase is associated with hepatotoxicity resulting in organ dysfunction in patients with preexisting liver disorders. This study investigated the protective effect of L-carnitine during chemotherapy in a steatotic rat liver model.
  
  
  METHODS
  Livers from nonsteatotic and steatotic rats were tested in an isolated liver reperfusion model adding L-asparaginase and L-carnitine to the reperfusate. Portal venous pressure (PVP), hepatic oxygen consumption, aspartate aminotransferase, lactate dehydrogenase, glutamate dehydrogenase and α-glutathione S-transferase levels were assessed. Further histopathological analysis was performed and cytotoxicity was verified in vitro.
  
  
  RESULTS
  L-Asparaginase induced toxicity in fatty livers whereas low toxicity was observed in normal livers. L-Carnitine induced a decline in PVP and oxygen consumption, and reduced parenchymal and mitochondrial damage in fatty livers. Cytotoxicity of L-asparaginase was not impaired by the presence of L-carnitine.
  
  
  CONCLUSIONS
  Our study emphasizes the potential of L-carnitine to reduce L-asparaginase-induced hepatotoxicity in patients with preexisting liver disorders.
authors.affiliation: Institute for Laboratory Animal Science, University Hospital, RWTH Aachen University, Aachen, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Roesmann
authors.forename: Mamdouh
authors.initials: M
authors.lastname: Afify
authors.forename: Jens
authors.initials: J
authors.lastname: Panse
authors.forename: Albrecht
authors.initials: A
authors.lastname: Eisert
authors.forename: Julia
authors.initials: J
authors.lastname: Steitz
authors.forename: Rene H
authors.initials: RH
authors.lastname: Tolba
mesh_terms: D000818:Animals; D001215:Asparaginase / Q000378:metabolism*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002331:Carnitine / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000209:etiology / Q000473:pathology*; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000201:enzymology / Q000473:pathology*; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014803:Vitamin B Complex / Q000494:pharmacology
chemical_list: D014803:Vitamin B Complex; D007770:L-Lactate Dehydrogenase; D005969:Glutamate Dehydrogenase; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D001215:Asparaginase; D002331:Carnitine