In vitro cytogenotoxic evaluation of sertraline

摘要

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, 0.01; r=–0.930, <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 H O . 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 oxidative stress on cultured human peripheral blood lymphocytes.