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

Autori
Lucić Vrdoljak, Ana ; Zandona, Antonio ; Jurič, Andreja ; Tariba Lovaković, Blanka ; Rašić, Dubravka ; Pizent, Alica ; Kopjar, Nevenka ; Kozina, Goran ; Brčić Karačonji, Irena

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
Conference Book of the Global Summit on Toxicology and Applied Pharmacology (TOXI2021) / - , 2021, 33-34

Skup
Global Summit on Toxicology and Applied Pharmacology (TOXI 2021)

Mjesto i datum
Marseille, Francuska, 11.11.2021. - 12.11.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
LSD ; PCP ; SH-SY5Y ; cell viability ; comet assay ; antioxidant enzymes, toxicity

Sažetak
Psychoactive substance abuse has been increasing worldwide over recent decades and is a significant burden to human health. The majority of these substances are taken orally, but also by smoking, inhalation or injection. Lysergic acid diethylamide (LSD) is a classical hallucinogen widely abused for decades, while the popularity of phencyclidine (PCP or “angel dust”) has increased in recent years, especially among adolescents. Both substances produce significant psychoactive, neurochemical, and behavioral effects. Up to now, very little has been known on the general toxicity of these compounds, especially their possible neurotoxic effects at cell level. This study assessed the toxic effects of LSD and PCP on human neuroblastoma cell line SH-SY5Y. To establish cytotoxic effects, cells were first exposed to the tested compounds at a concentration range of 0.039 – 100 µM for 24 h. Using MTS assay, we determined concentrations that reduced cell viability by up to 30%. Cells treated with these selected concentrations were then subjected to the alkaline comet assay, along with a battery of biochemical assays that enable the estimation of oxidative stress-related effects (lipid peroxidation, induction of reactive oxygen species – ROS, glutathione level, and activities of enzymes glutathione peroxidase – GPx, superoxide dismutase – SOD, and catalase – CAT). Treatment with LSD at 6.25 µM resulted in 88.06±2.05 % viable cells, while for PCP treatment with 3.13 µM in 84.17±3.19 % viable cells. These concentrations allowed for genotoxicity testing, which resulted in a statistically significant increase of comet tail length and tail intensity after LSD treatment, and a statistically significant increase of comet tail length after PCP treatment versus negative control. At the same tested concentrations, LSD caused a marked increase of malondialdehyde level, compared to control, contrary to PCP. While LSD induced significant increases in ROS production and glutathione level, PCP treatment led to significant decreases of these parameters compared to control. Treatment with LSD significantly enhanced activities of all antioxidant enzymes compared to control. Treatment with PCP resulted in significantly increased GPx and SOD activities, but CAT activity was significantly lower than in the respective control. Taken together, LSD had a greater DNA damaging potential and exerted stronger oxidative activity than PCP in SH-SY5Y cells. To our knowledge, this is the first study that investigated all of the above-mentioned outcomes of LSD and PCP in vitro, and its results could contribute to a better understanding of the toxicity profiles of both compounds. Funding: This research was supported by the programme of cooperation between the Institute for Medical Research and Occupational Health (Zagreb, Croatia) and the University North (Varaždin, Croatia).

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

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