<abstract xmlns="http://www.w3.org/1999/xhtml">Sertraline (SRT) is an antidepressant agent used as a neuronal selective serotonin-reuptake inhibitor (SSRI). SRT blocks serotonin reuptake and increases serotonin stimulation of somatodendritic serotonin 1A receptor (5-HT1AR) and terminal autoreceptors in the brain. In the present study, the genotoxic potential of SRT was evaluated using cytokinesis-block micronucleus (CBMN) cytome assay in peripheral blood lymphocytes of healthy human subjects. DNA cleavage-protective effects of SRT were analyzed on plasmid pBR322. In addition, biochemical parameters of total oxidant status (TOS) and total antioxidant status (TAS) in blood plasma were measured to quantitate oxidative stress. Human peripheral blood lymphocytes were exposed to four different concentrations (1.25, 2.5, 3.75 and 5 µg/mL) of SRT for 24- or 48-h treatment periods. In this study, SRT was not found to induce MN formation either in 24- or 48-h treatment periods. In contrast, SRT concentration-dependently decreased the percentage of MN and MNBN (r=−0.979, <italic>p</italic>&lt;0.01; r=−0.930, <italic>p</italic>&lt;0.05, respectively) when it was present for the last 48 hr (48-h treatment) of the culture period. SRT neither demonstrated a cleavage activity on plasmid DNA nor conferred DNA protection against H2O2. The application of various concentrations of SRT significantly increased the TOS and oxidative stress index (OSI) in human peripheral blood lymphocytes for both the 24- and 48-h treatment periods. Morover, the increase in TOS was potent as the positive control MMC at both treatment times. However, SRT did not alter the TAS levels in either 24- or 48-h treatment periods when compared to control. In addition, exposing cells to SRT caused significant decreases in the nuclear division index at 1.25, 2.50 and 3.75 µg/mL in the 24-h and at the highest concentration (5 µg/mL) in the 48-h treatment periods. Our results suggest that SRT may have cytotoxic effect <italic>via</italic> oxidative stress on cultured human peripheral blood lymphocytes.</abstract>

Sertraline (SRT) is an antidepressant agent used as a neuronal selective serotonin-reuptake inhibitor (SSRI). SRT blocks serotonin reuptake and increases serotonin stimulation of somatodendritic serotonin 1A receptor (5-HT1AR) and terminal autoreceptors in the brain. In the present study, the genotoxic potential of SRT was evaluated using cytokinesis-block micronucleus (CBMN) cytome assay in peripheral blood lymphocytes of healthy human subjects. DNA cleavage-protective effects of SRT were analyzed on plasmid pBR322. In addition, biochemical parameters of total oxidant status (TOS) and total antioxidant status (TAS) in blood plasma were measured to quantitate oxidative stress. Human peripheral blood lymphocytes were exposed to four different concentrations (1.25, 2.5, 3.75 and 5 µg/mL) of SRT for 24- or 48-h treatment periods. In this study, SRT was not found to induce MN formation either in 24- or 48-h treatment periods. In contrast, SRT concentration-dependently decreased the percentage of MN and MNBN (r=−0.979, p<0.01; r=−0.930, p<0.05, respectively) when it was present for the last 48 hr (48-h treatment) of the culture period. SRT neither demonstrated a cleavage activity on plasmid DNA nor conferred DNA protection against H2O2. The application of various concentrations of SRT significantly increased the TOS and oxidative stress index (OSI) in human peripheral blood lymphocytes for both the 24- and 48-h treatment periods. Morover, the increase in TOS was potent as the positive control MMC at both treatment times. However, SRT did not alter the TAS levels in either 24- or 48-h treatment periods when compared to control. In addition, exposing cells to SRT caused significant decreases in the nuclear division index at 1.25, 2.50 and 3.75 µg/mL in the 24-h and at the highest concentration (5 µg/mL) in the 48-h treatment periods. Our results suggest that SRT may have cytotoxic effect via oxidative stress on cultured human peripheral blood lymphocytes.

<italic>In vitro</italic> cytogenotoxic evaluation of sertraline

Faculty of Science and Letters, Department of Biology

Faculty of Medicine, Department of Medical Biology and Genetics

Interdisciplinary Toxicology

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

{"article-title":{"italic":"In vitro","content":"cytogenotoxic evaluation of sertraline"}}

Sertraline (SRT) is an antidepressant agent used as a neuronal selective serotonin-reuptake inhibitor (SSRI). SRT blocks serotonin reuptake and increases...

In vitro cytogenotoxic evaluation of sertraline

Online veröffentlicht: 18. Okt. 2019

Seitenbereich: 181 - 188

Eingereicht: 03. Nov. 2017

Akzeptiert: 15. Mai 2018

DOI: https://doi.org/10.2478/intox-2018-0015

Schlüsselwörter
sertraline, micronucleus, pBR322, peripheral blood lymphocytes, oxidative stress, cytotoxicity

© 2018 Interdisciplinary Toxicology, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

In vitro cytogenotoxic evaluation of sertraline

Online veröffentlicht: 18. Okt. 2019

Seitenbereich: 181 - 188

Eingereicht: 03. Nov. 2017

Akzeptiert: 15. Mai 2018

DOI: https://doi.org/10.2478/intox-2018-0015

Schlüsselwörtersertraline, micronucleus, pBR322, peripheral blood lymphocytes, oxidative stress, cytotoxicity

© 2018 Interdisciplinary Toxicology, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Schlüsselwörter
sertraline, micronucleus, pBR322, peripheral blood lymphocytes, oxidative stress, cytotoxicity