• Fluoxetine Induces Oxidative Stress Dependent DNA Damage in Human Hepatoma Cells
  • Somayyeh Boshtam,1,* Mohammad Shokrzadeh,2
    1. Student research committee, Pharmacy School, Mazandaran University of medical Sciences,Sari Iran
    2. Pharmaceutical Sciences Research Center, Mazandaran University of medical Sciences, Sari Iran


  • Introduction: Fluoxetine is a selective serotonin reuptake inhibitor is a commonly used drug for the treatment of major depression (MD). Despite the positive effects of this drug it seems to be associated with various side effects. Genotoxicity or DNA damage is an important side effect of different drugs in different categories. However, to date, the genotoxicity and cytotoxicity of Fluoxetine are partially unknown
  • Methods: In the present study ROS, MDA and GSH evaluation methods were used for oxidative stress detection in HepG2 cells treated with Fluoxetine (1-10μM). Comet assay tried to evaluate the genotoxic effects of Fluoxetine and Flow cytometry was also used to apoptosis detection in these hepatic cells
  • Results: Our data showed that 1h after treatment with Fluoxetine the MDA and intracellular concentration of ROS was increased significantly in a concentration-dependent manner (p<0.001).While the amount of GSH was reduced also significantly (p<0.001). Our results also clearly indicated that Fluoxetine treatment resulted in the increased DNA damage of HepG2 cells. Tail percentage of DNA for control cells was 4% but this percentage was 19%, 28% and 32% for 1, 5 and 10 µM of Fluoxetine, respectively (P<0.01 and P<0.001). Our data of flow cytometry also showed increasing the early and late apoptosis to 13.31% and 9.54%, respectively. In the concentration of 5 μM, the percentage of cells in early apoptosis was 40.25% and 40.52% in late apoptosis. Another concentration of Fluoxetine (10 μM) led to catastrophically increasing the early and late apoptosis to 25.49% and 48.75%, respectively
  • Conclusion: In conclusion, the present study showed that Fluoxetine is able to oxidative stress-dependent damage DNA. Therefore, due to the high incidence of depression, the genotoxic effects of Fluoxetine should be emphasized. However further study is needed to confirm our study.
  • Keywords: Fluoxetine, Genotoxicity, DNA damage, Depression, ROS, Apoptosis