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The role of calcium in paracetamol (acetaminophen) cytotoxicity in PC12 cells transfected with CYP4502E1.
MedLine Citation:
PMID:  17694370     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
Paracetamol-induced toxicity is mainly due to the accumulation of its CYP450-mediated N-hydroxylation product - N-acetylimidoquinone. We examined cell viability, proliferation rates and intracellular calcium in PC12 cells and in a PC12 cell line transfected with cytochrome P4502E1 exposed to paracetamol. This drug had a concentration-related effect on cell survival and a LD(50) which was significantly different between both cell types. A 48% decrease of PC12 cells was found following application of 5 mmol/L paracetamol for 48 h. A total 73% decrease in cell numbers was found in cells metabolizing the drug. Culture protein levels were diminished in a similar manner. Paracetamol increased intracellular calcium (by 662%) only in CYP4502E1-transfected cells. The protective role of EGTA and verapamil modulating calcium homeostasis was more evident in CYP4502E1-transfected cells. These results suggest that biotransformation of paracetamol by CYP2E1 increases its cytotoxicity and that a calcium imbalance may have a key role in the initiation of cell injury.
Authors:
A Holownia; J F Menez; J J Braszko
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Inflammopharmacology     Volume:  6     ISSN:  0925-4692     ISO Abbreviation:  Inflammopharmacology     Publication Date:  1998  
Date Detail:
Created Date:  2007-08-13     Completed Date:  2010-01-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9112626     Medline TA:  Inflammopharmacology     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  133-42     Citation Subset:  -    
Affiliation:
Medical Academy of Bialystok, Ludwik Zamenhof Children's Hospital, Clinical Pharmacology Unit, J. Waszyngtona 17, 15-274, Bialystok, Poland.
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