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, 29 (4), 558-68

An In Vitro Study of the Neurotoxic Effects of N-Benzylpiperazine: A Designer Drug of Abuse

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An In Vitro Study of the Neurotoxic Effects of N-Benzylpiperazine: A Designer Drug of Abuse

Karolina Persona et al. Neurotox Res.

Abstract

Recently, the number of new psychoactive substances has significantly increased. Despite the systematic introduction of prohibition in trade of medicinal products which mimic the effects of illegal drugs, the problem concerning this group of drugs is still important although knowledge about the mechanism of action of those types of substances is scarce. This study aimed to follow the neurotoxic effect of N-benzylpiperazine (BZP), the central nervous system psychostimulant, using the human cancer LN-18 cell model. The statistically significant elevation of LDH levels, increased mitochondrial membrane potential, decreased ATP and increased ROS production, increased levels of DNA damage marker (8-OHdG) and activation of caspases: -3 and -9 confirmed by Real-Time PCR imply the activation of mitochondrial proapoptotic pathways induced by BZP after 24 h incubation. This study is a novel, preliminary attempt to explain the toxicity of one of the most popular designer drug of abuse at the cellular level.

Keywords: Apoptosis; Benzylpiperazine; Neurodegeneration; New psychoactive substances; Oxidative stress.

Figures

Fig. 1
Fig. 1
The influence of the selected concentrations of BZP on: the changes in potential (ΔΨ m) of the inner mitochondrial membrane (n = 10–14; contr. (+): CCCP; system of random blocks: F(4, 42) = 5.7, p < 0.001; Dunnett’s test versus contr.: *p < 0.05); on the changes in ATP generation (n = 8; F(4, 28) = 10.4, p < 0.001; Dunnett’s test versus contr.: ***p < 0.001) in cell lines LN-18
Fig. 2
Fig. 2
Changes in ROS production in cells of the LN-18 line under the influence of BZP (n = 14; contr. (+) 1 mmol/L H2O2; system of randomized blocks: F(4, 52) = 18.1, p < 0.001; Dunnett’s test versus contr.: ***p < 0.001)
Fig. 3
Fig. 3
Influence of BZP on changes in the concentration of 8-OHdG in cell lines LN-18 (n = 3; system of randomized blocks: F(2, 4) = 99.7, p < 0.001; Dunnett’s test versus contr.: **p < 0.01; ***p < 0.001)
Fig. 4
Fig. 4
Influence of BZP on: caspase-3 activity (n = 5–6; system of random blocks: F(4, 22) = 27.6; p < 0.001; Dunnett’s test versus contr.: ***p < 0.001), caspase-9 activity (n = 5–6; F(4, 22) = 27.4; p < 0.001; Dunnett’s test versus contr.: *p < 0.05), caspase-8 activity (n = 5–6; F(4, 22) = 2.3; p < 0.05 in cell lines LN-18; contr.(−) cells were cultured in the presence of BZP at concentration of 300 µg/mL with the addition of the inhibitor
Fig. 5
Fig. 5
Influence of BZP on the changes in the level of relative gene expression. a BCL2/BAX; b NFκB1/RELA, c DDIT3/HSPA5, d SOD2/GPX3, and e CASP8/CASP9 in the cells of the LN-18 line (n = 3–4, pair-wise fixed randomisation Test© versus contr. *p < 0.05; ***p ≤ 0.001)

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