Study of neurotoxicity of paracetamol and its metabolite NAPQI (short message)

Yu.A. Vlasova1, ORCID 0000-0001-5536-3595
N.E. Golovanova1, 2, ORCID 0000-0001-9286-8787
Ch.R. Beishebaeva1ORCID 0000-0002-9245-6261
K.A. Zagorodnikova1ORCID 0000-0002-5251-5319
M.N. Sokolova1ORCID 0000-0002-6266-4342
V.A. Dadali1ORCID 0000-0002-1404-9396
Zh.V. Antonova1 , ORCID 0000-0003-1789-2503
1North-Western State Medical University named after I.I. Mechnikov,
195067, Russia, St. Petersburg, Piskarevskij Prospekt, 47, pav. 5;
2St Petersburg State University,
199034, Russia, St Petersburg, 7–9 Universitetskayа Emb.
E-mail: Yuliya.Vlasova@szgmu.ru

 

Abstract

Despite a fairly complete study of the efficacy and safety aspects of paracetamol (acetaminophen, APAP), there is still no consensus regarding the negative effect of the drug on the central nervous system.The results of retrospective studies evident the possible connection between the intake of paracetamol by women during pregnancy with the development of autism and delayed psycho-emotional development in newborn children. This research often meet with serious criticism, as many questions arise about the methods for assessing behavior disorders and the processing of research results. Therefore, the experimental data obtained on neuronal cells may become a sufficient basis to confirm or refute the assumptions about the neurotoxicity of paracetamol. The aim of our research is to study the effect of paracetamol and its metabolite NAPQI on cells of the PC12 neuronal line in comparison with the effect on the neurons of the cerebral cortex of rat embryos under conditions of oxidative stress induced by 0.3 mM hydrogen peroxide. The study of the effect of paracetamol and its metabolite NAPQI on cell viability was carried out by a method based on the reduction of 3-(4,5-dimethylthiazole-2-yl)-2,5-tetrazolium bromide (MTT method). It was shown that neurons of the rat cerebral cortex preincubation with 1 mg/ml of paracetamol for 24 hours and subsequent incubation with 0,3 mM hydrogen peroxide, both hydrogen peroxide and paracetamol itself reduce the viability of neurons. Co-incubation with paracetamol and hydrogen peroxide also reduces the viability of neurons. The same effect of paracetamol and its metabolite is observed during preincubation of paracetamol or NAPQI and hydrogen peroxide. Thus, in both models, we obtained results indicating the neurotoxic effect of paracetamol and its metabolite NAPQI. In addition, this study compared the two models for studying neurotoxicity. The use of the PC12 neuronal line is a good alternative to experiments on neurons of the cerebral cortex of rat embryos. The absolutely advantages of the PC12 line are the simplicity of cultivation, rapid cell growth, and the possibility of obtaining a large amount of material for research.

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Author’s Contribution

Vlasova Yu.A. – elaboration of the idea of the study, management and coordination of planning and implementation of the stud.
Golovanova N.E. – experimental work (in vivo); collection, analysis of data.
Beishebaeva Ch.R. – experimental work (in vitro); collection, analysis of data.
Zagorodnikova K.A. – methodology, realization, date collection and analysis, writing-original the text of the article.
Sokolova M.N. – analysis of scientific literature, writing the text.
Antonova Zh.V. –  analysis of scientific literature, revising the text.
Dadali V.A. –  a substantial contribution to the elaboration of the study concept, administrative support of the project, viewing and editing the text of the article.

Conflict of interest

The authors declare no conflicts of interest.

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