In vitro cytogenotoxic evaluation of sertraline

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.

Exploring the Relationship between Diamine Oxidase and Psychotropic Medications in Fibromyalgia Treatment, Finding No Reduction in Diamine Oxidase Levels and Activity except with Citalopram

“…A significant limitation of this study was that we could not evaluate all drugs used for different fibromyalgia symptoms, including amitriptyline and duloxetine. Another limitation of this study was the concentrations of sertraline tested, which, although based on previous in vitro studies [52], exhibited toxicity in this study; therefore, they should be tested at lower concentrations to assess their effects on DAO. Additionally, the cultured cells may have undergone gene expression or behavioural alterations due to the artificial conditions of their environment, including the absence of natural physical forces and the presence of growth factors different from those in living organisms.…”

“…MTT was converted by viable cells into a purple formazan product and the amount of formazan formed was proportional to the number of viable cells. Cells were incubated for 24 h in the presence of three increased concentrations of the different treatments: sertraline at doses of 4.08, 5.72, and 7.35 µM [52]; alprazolam at concentrations of 1, 5, and 15 µM [53]; lorazepam at doses of 1, 25, and 50 µM [54]; pregabalin at concentrations of 2.5, 12.5, and 25 mM [55]; paroxetine at doses of 10, 30, and 50 µM [56]; and with citalopram at doses of 1, 15, and 50 µM [57]. Following a 24 h incubation period, the treatments were withdrawn and MTT was introduced into each well.…”

Complex Effects of Sertraline and Citalopram on In Vitro Murine Breast Cancer Proliferation and on In Vivo Progression and Anxiety Level

“…The in vitro data are consistent with previous reports [ 10 ] showing that sertraline alone at concentrations of 20 µM or higher caused a dose-dependent decrease in cell viability while citalopram had no significant effect ( Figure 1 ). Notably, a recent study showed that sertraline may have cytotoxic effects on cultured human peripheral blood lymphocytes, via oxidative stress [ 25 ], thus the impact of sertraline on the viability of 4T1 breast cancer cells may be related to a cytotoxic effect rather than to an anti-proliferative effect.…”

Evaluation of Oxidant-Antioxidant Status of Fluvoxamine on Human Lymphocyte Cell Culture

“…İstifli et al demonstrated that administration of Sertraline, which is an SSRI used as an antidepressant, on human lymphocyte cell cultures by LD50 (5 μg/mL) and 3.75 μg/mL for 24 and 48 hours and observed as a result that TOS and OSI increased significantly (17). In the experimental animal models on which they applied lipopolysaccharides, Abdel-Salem et al observed that, with Fluvoxamine treatment, oxidative stress decreased, and antioxidant molecules were increased in liver and brain tissues (18).…”