Cytotoxic, genotoxic, and oxidative stress-related effects of lysergic acid diethylamide (LSD) and phencyclidine (PCP) in the human neuroblastoma SH-SY5Y cell line

Lysergic acid diethylamide (LSD) is a classic hallucinogen, widely abused for decades, while phencyclidine (PCP) has increased in popularity in recent years, especially among the adolescents. Very little is known about the general toxicity of these compounds, especially about their possible neurotox...

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Main Authors: Jurič Andreja, Zandona Antonio, Lovaković Blanka Tariba, Rašić Dubravka, Pizent Alica, Kozina Goran, Katalinić Maja, Vrdoljak Ana Lucić, Karačonji Irena Brčić
Format: Article
Language:English
Published: Sciendo 2021-12-01
Series:Arhiv za Higijenu Rada i Toksikologiju
Subjects:
Online Access:https://doi.org/10.2478/aiht-2021-72-3604
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author Jurič Andreja
Zandona Antonio
Lovaković Blanka Tariba
Rašić Dubravka
Pizent Alica
Kozina Goran
Katalinić Maja
Vrdoljak Ana Lucić
Karačonji Irena Brčić
author_facet Jurič Andreja
Zandona Antonio
Lovaković Blanka Tariba
Rašić Dubravka
Pizent Alica
Kozina Goran
Katalinić Maja
Vrdoljak Ana Lucić
Karačonji Irena Brčić
author_sort Jurič Andreja
collection DOAJ
description Lysergic acid diethylamide (LSD) is a classic hallucinogen, widely abused for decades, while phencyclidine (PCP) has increased in popularity in recent years, especially among the adolescents. Very little is known about the general toxicity of these compounds, especially about their possible neurotoxic effects at the cell level. The aim of this study was to address these gaps by assessing the toxic effects of 24-hour exposure to LSD and PCP in the concentration range of 0.39–100 μmol/L in the human neuroblastoma SH-SY5Y cell line. After cell viability was established, cells treated with concentrations that reduced their viability up to 30 % were further subjected to the alkaline comet assay and biochemical assays that enable estimation of oxidative stress-related effects. Treatment with LSD at 6.25 μmol/L and with PCP at 3.13 μmol/L resulted with 88.06±2.05 and 84.17±3.19 % of viable cells, respectively, and led to a significant increase in primary DNA damage compared to negative control. LSD also caused a significant increase in malondialdehyde level, reactive oxygen species (ROS) production, and glutathione (GSH) level, PCP significantly increased ROS but lowered GSH compared to control. Treatment with LSD significantly increased the activities of all antioxidant enzymes, while PCP treatment significantly increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) but decreased catalase (CAT) activity compared to control. Our findings suggest that LSD has a greater DNA damaging potential and stronger oxidative activity than PCP in SH-SY5Y cells.
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spelling doaj.art-6fa8d456f13543f5a7b03ab0f87330c02022-12-22T03:13:48ZengSciendoArhiv za Higijenu Rada i Toksikologiju1848-63122021-12-0172433334210.2478/aiht-2021-72-3604Cytotoxic, genotoxic, and oxidative stress-related effects of lysergic acid diethylamide (LSD) and phencyclidine (PCP) in the human neuroblastoma SH-SY5Y cell lineJurič Andreja0Zandona Antonio1Lovaković Blanka Tariba2Rašić Dubravka3Pizent Alica4Kozina Goran5Katalinić Maja6Vrdoljak Ana Lucić7Karačonji Irena Brčić81Institute for Medical Research and Occupational Health, Zagreb, Croatia1Institute for Medical Research and Occupational Health, Zagreb, Croatia1Institute for Medical Research and Occupational Health, Zagreb, Croatia1Institute for Medical Research and Occupational Health, Zagreb, Croatia1Institute for Medical Research and Occupational Health, Zagreb, Croatia2University Centre Varaždin, University North, Varaždin, Croatia1Institute for Medical Research and Occupational Health, Zagreb, Croatia1Institute for Medical Research and Occupational Health, Zagreb, Croatia1Institute for Medical Research and Occupational Health, Zagreb, CroatiaLysergic acid diethylamide (LSD) is a classic hallucinogen, widely abused for decades, while phencyclidine (PCP) has increased in popularity in recent years, especially among the adolescents. Very little is known about the general toxicity of these compounds, especially about their possible neurotoxic effects at the cell level. The aim of this study was to address these gaps by assessing the toxic effects of 24-hour exposure to LSD and PCP in the concentration range of 0.39–100 μmol/L in the human neuroblastoma SH-SY5Y cell line. After cell viability was established, cells treated with concentrations that reduced their viability up to 30 % were further subjected to the alkaline comet assay and biochemical assays that enable estimation of oxidative stress-related effects. Treatment with LSD at 6.25 μmol/L and with PCP at 3.13 μmol/L resulted with 88.06±2.05 and 84.17±3.19 % of viable cells, respectively, and led to a significant increase in primary DNA damage compared to negative control. LSD also caused a significant increase in malondialdehyde level, reactive oxygen species (ROS) production, and glutathione (GSH) level, PCP significantly increased ROS but lowered GSH compared to control. Treatment with LSD significantly increased the activities of all antioxidant enzymes, while PCP treatment significantly increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) but decreased catalase (CAT) activity compared to control. Our findings suggest that LSD has a greater DNA damaging potential and stronger oxidative activity than PCP in SH-SY5Y cells.https://doi.org/10.2478/aiht-2021-72-3604antioxidant enzymescell viabilitydna damagegshhallucinogenic drugspsychoactive substancesrostoxicityantioksidacijski enzimihalucinogene drogelsdoštećenje dnapcppsihoaktivne tvaritoksičnostvijabilnost stanica
spellingShingle Jurič Andreja
Zandona Antonio
Lovaković Blanka Tariba
Rašić Dubravka
Pizent Alica
Kozina Goran
Katalinić Maja
Vrdoljak Ana Lucić
Karačonji Irena Brčić
Cytotoxic, genotoxic, and oxidative stress-related effects of lysergic acid diethylamide (LSD) and phencyclidine (PCP) in the human neuroblastoma SH-SY5Y cell line
Arhiv za Higijenu Rada i Toksikologiju
antioxidant enzymes
cell viability
dna damage
gsh
hallucinogenic drugs
psychoactive substances
ros
toxicity
antioksidacijski enzimi
halucinogene droge
lsd
oštećenje dna
pcp
psihoaktivne tvari
toksičnost
vijabilnost stanica
title Cytotoxic, genotoxic, and oxidative stress-related effects of lysergic acid diethylamide (LSD) and phencyclidine (PCP) in the human neuroblastoma SH-SY5Y cell line
title_full Cytotoxic, genotoxic, and oxidative stress-related effects of lysergic acid diethylamide (LSD) and phencyclidine (PCP) in the human neuroblastoma SH-SY5Y cell line
title_fullStr Cytotoxic, genotoxic, and oxidative stress-related effects of lysergic acid diethylamide (LSD) and phencyclidine (PCP) in the human neuroblastoma SH-SY5Y cell line
title_full_unstemmed Cytotoxic, genotoxic, and oxidative stress-related effects of lysergic acid diethylamide (LSD) and phencyclidine (PCP) in the human neuroblastoma SH-SY5Y cell line
title_short Cytotoxic, genotoxic, and oxidative stress-related effects of lysergic acid diethylamide (LSD) and phencyclidine (PCP) in the human neuroblastoma SH-SY5Y cell line
title_sort cytotoxic genotoxic and oxidative stress related effects of lysergic acid diethylamide lsd and phencyclidine pcp in the human neuroblastoma sh sy5y cell line
topic antioxidant enzymes
cell viability
dna damage
gsh
hallucinogenic drugs
psychoactive substances
ros
toxicity
antioksidacijski enzimi
halucinogene droge
lsd
oštećenje dna
pcp
psihoaktivne tvari
toksičnost
vijabilnost stanica
url https://doi.org/10.2478/aiht-2021-72-3604
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