N-acetyl-p-benzoquinonimine metabolite as a factor of possible neurotoxicity of paracetamol

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Abstract

BACKGROUND: Currently, the possible negative effects of paracetamol on the central nervous system are widely discussed in the modern scientific literature. The relationship between the intake of paracetamol during pregnancy by women and the risk of autism spectrum disorders in their children is being studied. However, such conclusions are often met with serious criticism as there are many questions about the methods of assessing behavioral disorders and processing research results. Therefore, experimental data obtained on neuronal cells may be a sufficient ground to confirm or refute assumptions about the neurotoxicity of paracetamol and its metabolites.

AIM: To study the effect of paracetamol and its metabolite N-acetyl-p-benzoquinonimine (NAPQI) on the neurons of the cerebral cortex of fetal rats.

MATERIALS AND METHODS: The study of the effect of paracetamol and its metabolite NAPQI on cell viability has been carried out by a method based on the reduction of 3-(4,5-dimethylthiazole-2-yl)-2,5-tetrazolium bromide (MTT).

RESULTS: It has been shown that during preincubation of neurons in the cerebral cortex of the rats with paracetamol at a concentration of 1 mg/ml for 24 hours and subsequent incubation with 0.3 mM hydrogen peroxide, both hydrogen peroxide and paracetamol itself reduce the viability of neurons. Joint incubation with paracetamol and hydrogen peroxide also reduces the viability of neurons. The same effect of paracetamol and its metabolite is observed with the joint preincubation of paracetamol or NAPQI and hydrogen peroxide.

CONCLUSIONS: Paracetamol as well its metabolite NAPQI reduce the viability of neurons in the fetal cortex of rats.

About the authors

Yuliya A. Vlasova

North-Western State Medical University named after I.I. Mechnikov

Email: Yuliya.Vlasova@szgmu.ru
ORCID iD: 0000-0001-5536-3595
Scopus Author ID: 6701810182

PhD, Cand. Sci. (Biol.), Assistant Professor

Russian Federation, 47 Piskarevsky Ave., Saint Petersburg, 195067

Ksenia A. Zagorodnikova

North-Western State Medical University named after I.I. Mechnikov

Author for correspondence.
Email: ksenia.zagorodnikova@gmail.com
SPIN-code: 4669-2059

MD, Cand. Sci. (Med.), Assistant Professor

Russian Federation, 47 Piskarevsky Ave., Saint Petersburg, 195067

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2. Fig. 1. Metabolism of paracetamol. NAPQI — N-acetyl-p-benzoquinonimine; UDG — uridine-diphosphate (UDG)-glucuronosyl transferase

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3. Fig. 2. The effect of paracetamol and NAPQI on the survival of neurons in the cerebral cortex of the fetal rats. APAP — paracetamol; NAPQI — N-acetyl-p-benzoquinonimine

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4. Fig. 3. The effect of paracetamol and NAPQI on the change in the mitochondrial membrane potential of neurons in the cerebral cortex of the fetal rats. APAP — paracetamol; NAPQI — N-acetyl-p-benzoquinonimine

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Copyright (c) 2021 Vlasova Y.A., Zagorodnikova K.A.

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