Document Detail


Hepatotoxicity associated with lapatinib in an experimental rat model.
MedLine Citation:
PMID:  22100178     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
CONCLUSION: 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:
Umut Demirci; Suleyman Buyukberber; Guldal Yılmaz; Mustafa Kerem; Ugur Coskun; Aytug Uner; Meltem Baykara; Hatice Pasaoglu; Hatice Pasali; Mustafa Benekli
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-11-16
Journal Detail:
Title:  European journal of cancer (Oxford, England : 1990)     Volume:  48     ISSN:  1879-0852     ISO Abbreviation:  Eur. J. Cancer     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-12-30     Completed Date:  2012-02-16     Revised Date:  2013-03-06    
Medline Journal Info:
Nlm Unique ID:  9005373     Medline TA:  Eur J Cancer     Country:  England    
Other Details:
Languages:  eng     Pagination:  279-85     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
Affiliation:
Atatürk Education and Research Hospital, Department of Medical Oncology, Ankara, Turkey. drumutdemirci@gmail.com
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MeSH Terms
Descriptor/Qualifier:
Alanine Transaminase / analysis
Albumins / analysis
Analysis of Variance
Animals
Antineoplastic Agents / toxicity*
Disease Models, Animal
Drug-Induced Liver Injury / metabolism,  pathology
Lipoproteins, VLDL / analysis
Liver / drug effects*,  metabolism,  pathology
Liver Function Tests
Protein Kinase Inhibitors / toxicity*
Quinazolines / toxicity*
Rats
Rats, Sprague-Dawley
Triglycerides / analysis
Chemical
Reg. No./Substance:
0/Albumins; 0/Antineoplastic Agents; 0/Lipoproteins, VLDL; 0/Protein Kinase Inhibitors; 0/Quinazolines; 0/Triglycerides; 0VUA21238F/lapatinib; EC 2.6.1.2/Alanine Transaminase
Comments/Corrections
Erratum In:
Eur J Cancer. 2013 Feb;49(3):767
Note: Pasali, Hatice [corrected to Pasaoglu, Hatice]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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