Paracetamol treatment increases telomerase activity in rat embryonic liver cells

Abstract

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 (6 mmol/l) and high (15 mmol/l) concentrations of toxin for 24 h 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.

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

“…A few compounds bypass senescence in this specific manner—acetaminophen, cotinine, nitric oxide, Na-selenite and lead. Other chemicals known to alter senescence only are mostly unknown ( 86 , 88–91 , 338–341 ).…”

Assessment of telomerase activity in leukocytes of type�2 diabetes mellitus patients having or not foot ulcer: Possible correlation with other clinical parameters

“…Thus, our findings may pinpoint to the presence of some common clinical traits in diabetic patients with ulcer, but caution should be taken in the translation and extrapolation of the results due to certain limitations of the study: i) Patient group size is relatively small and thus the study needs to be extended in order to validate our data in larger populations; and ii) a great intra- and inter-group diversity exists in terms of drug treatment for diabetes itself, as well as for existing comorbidities, which may interfere with the measured clinical characteristics. Telomere length, for example, has been reported to be negatively affected by drugs ( 38 , 39 ) and telomerase activity increases with paracetamol administration in rat embryonic liver cells ( 40 ).…”

Cell Immortality: In Vitro Effective Techniques to Achieve and Investigate Its Applications and Challenges

“…Furthermore, the carcinogenic strength of basic aliphatic alkylating agents like alkylnitrosamides and alkylmethanesulfonates is directly associated with their capacity to modify the comparatively less reactive oxygen atoms in DNA, notably the O6 atom of guanine [ 143 ]. In addition there are data suggesting that acetaminophen activates telomerase [ 146 , 147 , 148 , 149 ], which could lead to the immortalization of cells. However, there are also data indicating that acetaminophen can inhibit CDK4 and CDK2, thus imposing a cell cycle checkpoint at G1 and effectively blocking cellular proliferation [ 140 ].…”