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The effects of ketamine on viability, primary DNA damage, and oxidative stress parameters in HepG2 and SH-SY5Y cells

Andreja Jurič
Andreja Jurič
, 
Blanka Tariba Lovaković
Blanka Tariba Lovaković
, 
Antonio Zandona
Antonio Zandona
, 
Dubravka Rašić
Dubravka Rašić
, 
Martin Češi
Martin Češi
, 
Alica Pizent
Alica Pizent
, 
Marijana Neuberg
Marijana Neuberg
, 
Irena Canjuga
Irena Canjuga
, 
Maja Katalinić
Maja Katalinić
, 
Ana Lucić Vrdoljak
Ana Lucić Vrdoljak
, 
Arnes Rešić
Arnes Rešić
 und 
Irena Brčić Karačonji
Irena Brčić Karačonji
   | 26. Juni 2023
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Article Category: Original article
Online veröffentlicht: 26. Juni 2023
Seitenbereich: 106 - 114
Eingereicht: 01. März 2023
Akzeptiert: 01. Juni 2023
DOI: https://doi.org/10.2478/aiht-2023-74-3727
© 2023 Andreja Jurič et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Figure 1

Mean (± SD) changes in the viability of HepG2 and SH-SY5Y cells exposed to ketamine (0.39–100 µmol/L) for 24 h relative to control (untreated cells). Concentrations found in human plasma upon analgesia (0.39 µmol/L), anaesthesia (6.25 µmol/L), and drug abuse (1.56 µmol/L) are framed in red. Positive control – staurosporine (2 µmol/L); &P<0.05; #P<0.01; $P<0.001; *P<0.0001 vs control (untreated cells)
Mean (± SD) changes in the viability of HepG2 and SH-SY5Y cells exposed to ketamine (0.39–100 µmol/L) for 24 h relative to control (untreated cells). Concentrations found in human plasma upon analgesia (0.39 µmol/L), anaesthesia (6.25 µmol/L), and drug abuse (1.56 µmol/L) are framed in red. Positive control – staurosporine (2 µmol/L); &P<0.05; #P<0.01; $P<0.001; *P<0.0001 vs control (untreated cells)

Figure 2

Changes in comet tail intensity of HepG2 and SH-SY5Y cells exposed to ketamine for 24 h relative to control (alkaline comet assay). Ketamine concentrations correspond to concentrations found in human plasma upon analgesia (0.39 µmol/L), anaesthesia (6.25 µmol/L), and drug abuse (1.56 µmol/L). Results are expressed as mean, median and range. Positive control – H2O2 treated cells (100 µmol/2L)2. *Statistically significant differences (P<0.05, ANOVA with post-hoc Tukey HSD test) vs control
Changes in comet tail intensity of HepG2 and SH-SY5Y cells exposed to ketamine for 24 h relative to control (alkaline comet assay). Ketamine concentrations correspond to concentrations found in human plasma upon analgesia (0.39 µmol/L), anaesthesia (6.25 µmol/L), and drug abuse (1.56 µmol/L). Results are expressed as mean, median and range. Positive control – H2O2 treated cells (100 µmol/2L)2. *Statistically significant differences (P<0.05, ANOVA with post-hoc Tukey HSD test) vs control

Figure 3

Changes in malondialdehyde (MDA) concentrations in HepG2 and SH-SY5Y cells exposed to ketamine for 24 h relative to control [ketamine concentrations correspond to concentrations found in human plasma upon analgesia (0.39 µmol/L), anaesthesia (6.25 µmol/L), and drug- abuse (1.56 µmol/L)]. Results are expressed as means ± SD and medians
Changes in malondialdehyde (MDA) concentrations in HepG2 and SH-SY5Y cells exposed to ketamine for 24 h relative to control [ketamine concentrations correspond to concentrations found in human plasma upon analgesia (0.39 µmol/L), anaesthesia (6.25 µmol/L), and drug- abuse (1.56 µmol/L)]. Results are expressed as means ± SD and medians

Figure 4

Changes in ROS levels in HepG2 and SH-SY5Y cells exposed to ketamine for 24 h relative to control [ketamine concentrations correspond to concentrations found in human plasma upon analgesia (0.39 µmol/L), anaesthesia (6.25 µmol/L), and drug abuse (1.56 µmol/L)]. Results are expressed as mean ± SD and medians. ROS – reactive oxygen species determined using a fluorescent dye 2’,7’-dichlorodihydrofluorescein diacetate (DCFH-DA)
Changes in ROS levels in HepG2 and SH-SY5Y cells exposed to ketamine for 24 h relative to control [ketamine concentrations correspond to concentrations found in human plasma upon analgesia (0.39 µmol/L), anaesthesia (6.25 µmol/L), and drug abuse (1.56 µmol/L)]. Results are expressed as mean ± SD and medians. ROS – reactive oxygen species determined using a fluorescent dye 2’,7’-dichlorodihydrofluorescein diacetate (DCFH-DA)

Figure 5

Changes in glutathione (GSH) levels in HepG2 and SH-SY5Y cells exposed to ketamine for 24 h relative to control [ketamine concentrations correspond to concentrations found in human plasma relevant upon analgesia (0.39 µmol/L), anaesthesia (6.25 µmol/L), and drug abuse (1.56 µmol/L)]. Results are expressed as means ± SD and medians
Changes in glutathione (GSH) levels in HepG2 and SH-SY5Y cells exposed to ketamine for 24 h relative to control [ketamine concentrations correspond to concentrations found in human plasma relevant upon analgesia (0.39 µmol/L), anaesthesia (6.25 µmol/L), and drug abuse (1.56 µmol/L)]. Results are expressed as means ± SD and medians

Figure 6

Changes in glutathione peroxidase (GPx) activity in HepG2 and SH-SY5Y cells exposed to ketamine for 24 h relative to control [ketamine concentrations correspond to concentrations found in human plasma relevant upon analgesia (0.39 µmol/L), anaesthesia (6.25 µmol/L), and drug abuse (1.56 µmol/L)]. Results are expressed as means ± SD and medians. * P<0.05 vs control (ANOVA with post-hoc Tukey HSD test)
Changes in glutathione peroxidase (GPx) activity in HepG2 and SH-SY5Y cells exposed to ketamine for 24 h relative to control [ketamine concentrations correspond to concentrations found in human plasma relevant upon analgesia (0.39 µmol/L), anaesthesia (6.25 µmol/L), and drug abuse (1.56 µmol/L)]. Results are expressed as means ± SD and medians. * P<0.05 vs control (ANOVA with post-hoc Tukey HSD test)

Figure 7

Changes in superoxide dismutase (SOD) levels in HepG2 and SH-SY5Y cells exposed to ketamine for 24 h relative to control [ketamine concentrations correspond to concentrations found in human plasma relevant upon analgesia (0.39 µmol/L), anaesthesia (6.25 µmol/L), and drug abuse (1.56 µmol/L)]. Results are expressed as means ± SD and medians. *P<0.05 vs control (Kruskal-Wallis one-way analysis)
Changes in superoxide dismutase (SOD) levels in HepG2 and SH-SY5Y cells exposed to ketamine for 24 h relative to control [ketamine concentrations correspond to concentrations found in human plasma relevant upon analgesia (0.39 µmol/L), anaesthesia (6.25 µmol/L), and drug abuse (1.56 µmol/L)]. Results are expressed as means ± SD and medians. *P<0.05 vs control (Kruskal-Wallis one-way analysis)

Figure 8

Changes in catalase (CAT) levels in HepG2 and SH-SYY cells exposed to ketamine for 24 h relative to control [ketamine concentrations correspond to concentrations found in human plasma relevant upon analgesia (0.39 µmol/L), anaesthesia (6.25 µmol/L), and drug abuse (1.56 µmol/L)]. Results are expressed as means ± SD and medians. *P<0.05 vs control (ANOVA with post-hoc Tukey HSD test)
Changes in catalase (CAT) levels in HepG2 and SH-SYY cells exposed to ketamine for 24 h relative to control [ketamine concentrations correspond to concentrations found in human plasma relevant upon analgesia (0.39 µmol/L), anaesthesia (6.25 µmol/L), and drug abuse (1.56 µmol/L)]. Results are expressed as means ± SD and medians. *P<0.05 vs control (ANOVA with post-hoc Tukey HSD test)
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