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Assessment of usnic acid toxicity in rat primary hepatocytes using ¹³C isotopomer distribution analysis of lactate, glutamate and glucose.

ABSTRACT: 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 UA-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 10 ?M 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 1 ?M UA exposure did not appear to cause significant change in cell viability compared to controls. However, the 5 and 10 ?M UA concentrations significantly reduced cell viability as exposure time increased. Similar results were obtained for ATP depletion experiments. The 1 and 5 ?M UA doses suggest increased oxidative phosphorylation. Conversely, oxidative phosphorylation and gluconeogenesis were dramatically inhibited by 10 ?M UA. Augmented oxidative phosphorylation at the lower UA concentrations may be an adaptive response by the cells to compensate for diminished mitochondrial function.

SUBMITTER: Sonko BJ

PROVIDER: S-EPMC5753584 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Assessment of usnic acid toxicity in rat primary hepatocytes using ¹³C isotopomer distribution analysis of lactate, glutamate and glucose.

Sonko Bakary J BJ Schmitt Thomas C TC Guo Lei L Shi Qiang Q Boros Laszlo G LG Leakey Julian E A JE Beger Richard D RD

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 20110723 11

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 UA-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 10 μM UA ...[more]

PMID: 21802472

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Dataset Information

Assessment of usnic acid toxicity in rat primary hepatocytes using ¹³C isotopomer distribution analysis of lactate, glutamate and glucose.

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Assessment of usnic acid toxicity in rat primary hepatocytes using ¹³C isotopomer distribution analysis of lactate, glutamate and glucose.

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