Genotoxic evaluation of the active ingredients of antidepressant drugs, trazodone and milnacipran in human peripheral lymphocytes


Thesis Type: Postgraduate

Institution Of The Thesis: Gazi Üniversitesi, Fen Bilimleri Enstitüsü, Turkey

Approval Date: 2012

Student: ECE AVULOĞLU

Supervisor: DENİZ YÜZBAŞIOĞLU

Abstract:

Trazodone and Milnacipran are two active ingredients in antidepressant drugs which are used in the treatment of psychiatric disorders. In this study, the in vitro genotoxic effects of Trazodone and Milnacipran have been determined in human peripheral blood lymphocytes by using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), micronuclei (MN) and comet assays. The effects of Trazodone and Milnacipran on mitotic index (MI), replication index (RI) and nuclear division index were also investigated. 3,13; 6,25; 12,50; 25,00; 50,00 and 75,00 µg/ml concentrations of Trazodone and 2,5; 5,00; 10,00; 20,00; 30,00 and 40,00 µg/ml concentrations of Milnacipran were used. Trazodone significantly increased the frequency of chromosome aberrations and sister chromatid exchanges compared with the negative and solvent control. The other active ingredient Milnacipran raised the chromosome aberrations and sister chromatid exchanges frequencies compared to negative control. Trazodone increased the MN frequency in all concentrations but this increase was statistically significant at the three highest concentrations (25,00; 50,00 and 75,00 ?g/ml) compared to negative control. Compared to solvent control, this increase was not significant in all concentrations. Milnacipran significantly increased the frequency of micronuclei in all concentrations (except to 2,5 ?g/ml) in a dose dependent manner. Mitotic index was significantly decreased at all treatments but this decrease is not dose dependent (except treatment of Trazodone for 24 h). Replication and nuclear division indices were not effected at all treatments. According to the comet assay results Trazodone statistically increased mean comet tail intensity, tail length and tail moment at three concentrations (6,25; 12,50 and 25,00 ?g/ml; but 6,25 µg/ml for tail lenght compared with solvent control) compared with negative and solvent control. Two highest concentrations (50 and 75 ?g/ml) of Trazodone were toxic in comet assay. Milnacipran increased the comet tail intensity, tail length and tail moment at all concentrations. It is concluded that Trazodone and Milnacipran have clastogenic, mutagenic, aneugenic and cytotoxic effects on human lymphocytes in vitro.