title: Hepatotoxicity associated with lapatinib in an experimental rat model.
abstract: BACKGROUND
  The current study is the first to evaluate the biochemical and histopathological features of hepatic toxicity of lapatinib.
  
  
  METHODS
  Twenty Wistar albino rats were allocated into three groups: experimental toxicity was induced with lapatinib (10mg/kg) administered for 28 days (Group 1), 42 days (Group 2) orally in a single dose by gavage. Control group received only sterile water. Rats in Group 1 and Group 2 were sacrificed after the collection of blood and tissue samples on the 28th and 42nd days, respectively.
  
  
  RESULTS
  Subjects in Group 1 and Group 2 had significantly higher levels of alanin aminotransferase (ALT), albumin, triglyceride and very low density lipoprotein (VLDL) when compared with the control group. None of the subjects in the two experimental groups showed normal histology. There were parenchymal acinar transformation zones, sinusoidal dilatation, hydropic degeneration of hepatocytes, vacuolisation of hepatocytes around the portal areas, and mild inflammation with dominance of mononuclear cells besides neutrophil and eosinophil leucocytes in portal areas, especially pronounced in Group 2.
  
  
  CONCLUSIONS
  This study demonstrated that lapatinib brings about deterioration of lipid profile and triggers hepatic toxicity mainly as sinusoidal injury with elevation in transaminase levels, especially ALT.
authors.affiliation: Atatürk Education and Research Hospital, Department of Medical Oncology, Ankara, Turkey. drumutdemirci@gmail.com
authors.forename: Umut
authors.initials: U
authors.lastname: Demirci
authors.forename: Suleyman
authors.initials: S
authors.lastname: Buyukberber
authors.forename: Guldal
authors.initials: G
authors.lastname: Yılmaz
authors.forename: Mustafa
authors.initials: M
authors.lastname: Kerem
authors.forename: Ugur
authors.initials: U
authors.lastname: Coskun
authors.forename: Aytug
authors.initials: A
authors.lastname: Uner
authors.forename: Meltem
authors.initials: M
authors.lastname: Baykara
authors.forename: Hatice
authors.initials: H
authors.lastname: Pasaoglu
authors.forename: Hatice
authors.initials: H
authors.lastname: Pasali
authors.forename: Mustafa
authors.initials: M
authors.lastname: Benekli
mesh_terms: D000410:Alanine Transaminase / Q000032:analysis; D000418:Albumins / Q000032:analysis; D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D000077341:Lapatinib; D008079:Lipoproteins, VLDL / Q000032:analysis; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D047428:Protein Kinase Inhibitors / Q000633:toxicity*; D011799:Quinazolines / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000032:analysis
chemical_list: D000418:Albumins; D000970:Antineoplastic Agents; D008079:Lipoproteins, VLDL; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D014280:Triglycerides; D000077341:Lapatinib; D000410:Alanine Transaminase