Antidepressants are widely used for the symptomatic treatment of depressive disorder. Numerous current research on depression has contributed to the advancement of drug therapy and the emergence of new antidepressant drugs. Current guidelines for genotoxicity testing of new drugs suggests the important utility of assays that detect DNA damage, or tests to evaluate the induction of DNA breakage. However, the small number of data on the genotoxicity of drugs causes the number of drugs that can actually be used safely is reduced. Therefore, it is of utmost importance genotoxicology studies on the evaluation of drugs, especially drugs used for a long period of time such as antidepressants. Duloxetine is a new antidepressant belonging to the class of selective serotonin reuptake inhibitors of serotonin and norepinephrine (SNRIs), used in the symptomatic treatment of depression. Despite the existence of studies showing that some antidepressant drugs are genotoxic, there is to date no study on the possible genotoxicity of duloxetine in human cells. Thus, this study aims to explore the possible genotoxic potential of duloxetine in vitro in primary cultures of human lymphocytes through the techniques of detection of chromosomal aberrations and micronuclei. Primary cultures of blood lymphocytes of healthy volunteers were exposed to different concentrations of duloxetine (10-150 ng/ml) and cyclophosphamide (6 μg/ml) as a positive control. Structural chromosomal aberrations, mitotic index, nuclear division index, index binucleation, number of cells with one, two, three and four micronuclei and the number of cells with nucleoplasmáticas bridges were evaluated. All cultures incubated with indices of duloxetine were significantly lower than those of the control groups, indicating a degree of cytotoxicity of the drug. However, only concentrations of 100 and 150 ng/ml caused a significant increase in the presence of chromosomal aberrations and micronuclei. Whereas these concentrations are close to the upper limit of the therapeutic range of the drug used in humans, our results call already on the need to deepen their understanding of human genotoxicity of duloxetine.
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