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 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 μmolL 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 μmolL and with PCP at 3.13 μmolL 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. Dietilamid lizerginske kiseline (LSD) klasični je halucinogen koji se desetljećima naširoko zlorabio, dok je posljednjih godina porasla popularnost fenciklidina (PCP), osobito među adolescentima. Do sada se vrlo malo zna o općoj toksičnosti ovih spojeva, posebice o njihovim mogućim neurotoksičnim učincima na staničnoj razini. Ovo istraživanje procijenilo je toksične učinke LSD-a i PCP-a na staničnu liniju humanoga neuroblastoma SH-SY5Y, koja je bila izložena ispitivanim spojevima u rasponu koncentracija 0,39–100 μmolL tijekom 24 sata. Stanice tretirane odabranim koncentracijama koje su smanjile vijabilnost stanica do 30 % potom su podvrgnute alkalnom komet-testu i biokemijskim testovima koji omogućuju procjenu oksidacijskoga stresa. Tretman s LSD-om od 6,25 μmolL i PCP-om s 3,13 μmolL rezultirao je s 88,06±2,05 % odnosno 84,17±3,19 % vijabilnih stanica. Ove koncentracije omogućile su ispitivanje genotoksičnosti, što je rezultiralo značajnim povećanjem primarnog oštećenja DNA nakon tretmana LSD-om i PCP-om u odnosu na negativnu kontrolu. LSD je izazvao značajno povećanje razine malondialdehida u usporedbi s kontrolom, za razliku od PCP-a. Dok je LSD inducirao značajno povećanje proizvodnje reaktivnih kisikovih vrsta (ROS) i razine glutationa (GSH), tretman PCP-om uzrokovao je značajno povećanje proizvodnje ROS-a, ali smanjenje razine GSH-a u usporedbi s kontrolom. Tretman stanica LSD-om značajno je povećao aktivnosti svih antioksidacijskih enzima u usporedbi s kontrolom. Tretman PCP-om značajno je povećao aktivnosti glutation peroksidaze (GPx) i superoksid dismutaze (SOD), ali je aktivnost katalaze (CAT) bila značajno niža nego u odgovarajućoj kontroli. Zaključno, LSD je imao veći potencijal oštećenja DNA i pokazao je jaču oksidacijsku aktivnost od PCP-a u stanicama SH-SY5Y.