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Assessment of usnic acid toxicity in rat primary hepatocytes using (13)C isotopomer distribution analysis of lactate, glutamate and glucose.
MedLine Citation:
PMID:  21802472     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The lichen metabolite usnic acid (UA) has been promoted as a dietary supplement for weight loss, although cases of hepatotoxicity have been reported. Here we evaluated usnic acid-associated hepatotoxicity in vitro using isolated rat hepatocytes. We measured cell viability and ATP content to evaluate UA induced cytotoxicity and applied (13)C isotopomer distribution measuring techniques to gain a better understanding of glucose metabolism during cytotoxicity. The cells were exposed to 0, 1, 5 or 10μM UA concentrations for 2, 6 or 24h. Aliquots of media were collected at the end of these time periods and the (13)C mass isotopomer distribution determined for CO(2), lactate, glucose and glutamate. The 1μM UA exposure did not appear to cause significant change in cell viability compared to controls. However, the 5 and 10μM UA concentrations significantly reduced cell viability as exposure time increased. Similar results were obtained for ATP depletion experiments. The 1 and 5μM UA doses suggest increased oxidative phosphorylation. Conversely, oxidative phosphorylation and gluconeogenesis were dramatically inhibited by 10μM UA. Augmented oxidative phosphorylation at the lower UA concentrations may be an adaptive response by the cells to compensate for diminished mitochondrial function.
Authors:
Bakary J Sonko; Thomas C Schmitt; Lei Guo; Qiang Shi; Laszlo G Boros; Julian E A Leakey; Richard D Beger
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-23
Journal Detail:
Title:  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association     Volume:  -     ISSN:  1873-6351     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-8-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8207483     Medline TA:  Food Chem Toxicol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Ltd.
Affiliation:
Division of Systems Biology, National Center for Toxicological Research, US FDA, Jefferson, AR 72079, USA.
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