Agomelatine’s effect on human genetic material: in vitro study

Georgios Demirtzoglou, Sofia-Ifigeneia Chrysoglou, Dimos Dimellis, Zafiroula Iakovidou-Kritsi

Abstract


Introduction: Agomelatine is a prescription drug approved for the treatment of major depressive disorder. It is a melatonergic agonist and a 5-HT2C antagonist. The cytogenetic behavior of agomelatine has not been studied. The aim of the present study is the investigation of the in vitro effect of agomelatine on human DNA, by estimating sensitive cytogenetic indices. Methods: SCEs (Sister Chromatid Exchanges) are considered as one of the most sensitive markers of genotoxicity, PRI (Proliferation Rate Index) is one of the most reliable markers of cytostatic activity, whereas MI (Mitotic Index) shows precisely the ability of the cell to proliferate. We have investigated the effect of five agomelatine solutions on SCEs, PRI and MI of human cultured lymphocytes stained with the Fluorescence plus Giemsa method and estimated with the optical microscope. Results: Analysis of the results has revealed statistically significant (p<0.001) dose-dependent increase of SCE frequencies and significant reduction of PRI and MI values on lymphocyte cultures treated with agomelatine. Furthermore, a correlation was observed between a) the magnitude of the SCE induction and the PRI alterations, b) the magnitude of the MI alterations and the SCE induction and c) the magnitude of PRI alterations and MI alterations. Conclusions:Agomelatine at therapeutic doses exhibited dose-dependent cytogenetic activity in vitro. This may provide additional information about the mechanism of action of the drug. Considering that the use of agomelatine has rapidly increased, further studies in other cell lines and in vivo experimental settings are needed in order to evaluate its effect on human genetic material.


Keywords


Agomelatine, Cytogenetic Activity, Sister Chromatid Exchanges, Proliferation Rate Index, Mitotic Index

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