Fluoxetine induces oxidative stress-dependent DNA damage in human hepatoma cells

Somayeh Boshtam; Mohammad Shokrzadeh; Nasrin Ghassemi-Barghi; Somayeh Boshtam; Mohammad Shokrzadeh; Nasrin Ghassemi-Barghi

doi:10.3934/medsci.2023007

AIMS Medical Science

2023, Volume 10, Issue 1: 69-79. doi: 10.3934/medsci.2023007

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Research article

Fluoxetine induces oxidative stress-dependent DNA damage in human hepatoma cells

Running title: Fluoxetine-induced DNA damage in HepG2 cells

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

Received: 27 July 2022 Revised: 01 March 2023 Accepted: 12 March 2023 Published: 30 March 2023

Fluoxetine is a selective serotonin reuptake inhibitor that is a commonly used drug for the treatment of depression and obsessive-compulsive disorders. 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 some kinds of drugs. To date, the genotoxicity and cytotoxicity of fluoxetine are partially unknown. In the present study, some oxidative stress methods were used, such as ROS, MDA and GSH evaluation methods in HepG2 cells treated with fluoxetine (1–10 µM). A comet assay was used to evaluate the genotoxic effects of fluoxetine, and flow cytometry was used for apoptosis detection in these hepatic cells. Our data have shown that fluoxetine increased MDA and intracellular concentration of ROS significantly (P < 0.001), while the amount of GSH was reduced significantly (P < 0.001). Our results also indicated that fluoxetine increased the DNA damage of HepG2 cells. The 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 concentration, respectively (P < 0.01 and P < 0.001). The flow cytometry results have also shown increases in early and late apoptosis for fluoxetine (13.31% and 9.54%, respectively). In conclusion, the present study has shown that fluoxetine is able to induce oxidative stress-dependent DNA damage. Anyway, more studies are needed to accurately explore the molecular and cellular aspects of fluoxetine.
- fluoxetine,
- genotoxicity,
- DNA damage,
- depression,
- ROS,
- apoptosis
Citation: Somayeh Boshtam, Mohammad Shokrzadeh, Nasrin Ghassemi-Barghi. Fluoxetine induces oxidative stress-dependent DNA damage in human hepatoma cells[J]. AIMS Medical Science, 2023, 10(1): 69-79. doi: 10.3934/medsci.2023007

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Abstract

Fluoxetine is a selective serotonin reuptake inhibitor that is a commonly used drug for the treatment of depression and obsessive-compulsive disorders. 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 some kinds of drugs. To date, the genotoxicity and cytotoxicity of fluoxetine are partially unknown. In the present study, some oxidative stress methods were used, such as ROS, MDA and GSH evaluation methods in HepG2 cells treated with fluoxetine (1–10 µM). A comet assay was used to evaluate the genotoxic effects of fluoxetine, and flow cytometry was used for apoptosis detection in these hepatic cells. Our data have shown that fluoxetine increased MDA and intracellular concentration of ROS significantly (P < 0.001), while the amount of GSH was reduced significantly (P < 0.001). Our results also indicated that fluoxetine increased the DNA damage of HepG2 cells. The 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 concentration, respectively (P < 0.01 and P < 0.001). The flow cytometry results have also shown increases in early and late apoptosis for fluoxetine (13.31% and 9.54%, respectively). In conclusion, the present study has shown that fluoxetine is able to induce oxidative stress-dependent DNA damage. Anyway, more studies are needed to accurately explore the molecular and cellular aspects of fluoxetine.

Conflict of interest

All authors declare no conflict of interest regarding the publication of this paper.

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