Evaluation of venlafaxine and mirtazapine toxicity in male reproductive cell lines

Determining the toxic/adverse effects that drugs induce on different systems secondary to the impact of their use in treatment is of great importance in terms of drug safety. Drugs that can cause undesirable effects on many systems can affect fertility in both women and men. It is inevitable that medications used in repeated doses, especially during reproductive ages, will affect fertility. In addition to a small number of studies evaluating the undesirable effects of the serotonin-noradrenaline reuptake inhibitor antidepressant drug venlafaxine and the atypical antidepressant drug mirtazapine on the male reproductive system, it was determined that there were no studies demonstrating their effects on the reproductive system at the cellular level. From this point of view, this thesis aimed to investigate the in vitro reproductive toxicity of venlafaxine and mirtazapine in TM3 (mouse testis Leydig cell line) cell lines and to elucidate the mechanism of possible toxicity. In this study, dose-dependent cell viability on TM3 Leydig cells was tested by MTT assay and inhibitory concentration 50 was determined. Based on this concentration, Annexin V/Propidium Iodide apoptosis assay was performed to determine apoptosis and Dichlorofluorescein-diacetate method was applied to determine reactive oxygen species production. Exposure of TM3 Leydig cells to high concentrations of venlafaxine for 24 and 48 hours did not cause a significant cytotoxic effect, whereas mirtazepine caused a cytotoxic effect. Mirtazepine triggered apoptotic cell death and induced reactive oxygen species production in TM3 Leydig cells. In conclusion, basic findings indicating reproductive toxicity were obtained with mirtazepine but not with venlafaxine.