Paracetamol treatment increases telomerase activity in rat embryonic liver cells

Although paracetamol is known to have a damaging effect, this pharmaceutical is widely applied to pregnant and lactating women. Despite substantial progress in our understanding of its hepatotoxicity, some mechanisms, particularly of its embryonal and developmental toxicity, are still unknown. Thus,...

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Bibliographic Details
Published in:Pharmacological reports 2011, Vol.63 (6), p.1435-1441
Main Authors: Bader, Augustinus, Oliver, Petters, Keller, Mario, Pavlica, Sanja
Format: Article
Language:English
Subjects:
Acetaminophen - pharmacology
Animals
Cell Line
Dose-Response Relationship, Drug
Drug Safety and Pharmacovigilance
Enzyme Activation - drug effects
Enzyme Activation - physiology
Hepatocytes - drug effects
Hepatocytes - enzymology
hepatotoxicity
Liver - drug effects
Liver - embryology
Liver - enzymology
liver progenitors
paracetamol
Pharmacotherapy
Pharmacy
Rats
Telomerase - metabolism
telomerase activity
Treatment Outcome
Up-Regulation - drug effects
Up-Regulation - physiology
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Summary:Although paracetamol is known to have a damaging effect, this pharmaceutical is widely applied to pregnant and lactating women. Despite substantial progress in our understanding of its hepatotoxicity, some mechanisms, particularly of its embryonal and developmental toxicity, are still unknown. Thus, cell culture assays that investigate its toxicity are of particular interest. We assessed the effects of acute paracetamol treatment on cell viability (LDH assay, MTT assay), glutathione content (GSH assay), metabolic status (albumin and urea assays) and telomerase activity using rat embryonic liver cells (RLC-18 cells). Incubation with low (6mmol/l) and high (15mmol/l) concentrations of toxin for 24h leads to 20% and 50% cytotoxicity, respectively. Paracetamol exerted its toxicity in a similar pathway (depletion of GSH stores) as in adult liver cells, producing damage at the cellular level. Interestingly, paracetamol treatment significantly enhanced telomerase activity. Mechanisms involved in paracetamol-induced inhibition of cell senescence should be further elucidated. Telomerase activity in RLC-18 cells offers unique opportunities for examining basic biologic mechanisms. Our findings should encourage further studies to investigate a link between telomerase activity and toxicity, implying a role of impaired telomerase activity in human pathology.
ISSN:1734-1140
2299-5684
DOI:10.1016/S1734-1140(11)70707-1