Evaluation of cytogenetic and DNA damage induced by the antidepressant drug-active ingredients, trazodone and milnacipran,in vitro

Abstract

Trazodone and milnacipran are the active antidepressant drugs that are being 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 chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), micronuclei (MN), and comet assays. 3.13; 6.25; 12.50; 25.00; 50.00; and 75.00 μg/mL concentrations of trazodone and 2.50; 5.00; 10.00; 20.00; 30.00; and 40.00 μg/mL concentrations of milnacipran were used. Trazodone and milnacipran significantly increased the frequency of CAs and SCEs compared with the control. Both of the active ingredients raised the MN frequency in a dose-dependent manner. Mitotic index was significantly decreased, but replication and nuclear division indices were not affected at all treatments. Trazodone was statistically increased the mean comet tail intensity, tail length, and tail moment at three concentrations (6.25; 12.50; and 25.00 μg/mL) compared with control. Two highest concentrations (50 and 75 μg/mL) of trazodone were toxic in the 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, and cytotoxic effects on human lymphocytes in vitro.

Assessment of trazodone-induced cardiotoxicity after repeated doses in rats

“…80 –83 Comet, micronucleus, chromosomal aberration, and sister chromatid exchange assays are commonly used to determine the mutagenic and genotoxic effects induced by xenobiotics. 84 –87 Although studies are insufficient to investigate the genotoxic effects of TRZ, it has been shown that trazodone have clastogenic and mutagenic effects on human lymphocytes in vitro. 85 According to the results of our study, there was a significant increase in tail moment indicating DNA damage in TRZ-administered rats.…”

“…84 –87 Although studies are insufficient to investigate the genotoxic effects of TRZ, it has been shown that trazodone have clastogenic and mutagenic effects on human lymphocytes in vitro. 85 According to the results of our study, there was a significant increase in tail moment indicating DNA damage in TRZ-administered rats. Besides, increasing oxidative stress in cardiac tissue may induce structural changes such as cardiomyopathy, cardiac hypertrophy, and dysfunction of contractile protein.…”

Tanshinone-IIA-Based Analogues of Imidazole Alkaloid Act as Potent Inhibitors To Block Breast Cancer Invasion and Metastasis in Vivo

“…Subsequently, we detected the induction of DSBs in MDA-MB-231 cells by neutral comet assays and confocal immunofluorescence assays, stained with DSB biomarker γH2AX . Part A of Figure shows that TA12 significantly increased the generation of endogenous DSBs in MDA-MB-231 cells, as indicated by the statistical increase in olive tail moment . The percentages of γH2AX focal positive cells were obviously increased in MDA-MB-231 cells treated with different concentrations of TA12 (0, 10, and 20 μM).…”

“…41 Part A of Figure 7 shows that TA12 significantly increased the generation of endogenous DSBs in MDA-MB-231 cells, as indicated by the statistical increase in olive tail moment. 42 The percentages of γH2AX focal positive cells were obviously increased in MDA-MB-231 cells treated with Reactive oxygen species (ROS) plays an important role in the induction of DNA damage. 43 We speculated the possibility that overproduced ROS induced by TA12 entered into nucleus to enhance ROS-mediated DNA damage.…”

How antidepressants affect the cerebral ischemic injury and ischemic stroke

“…SNRIs such as duloxetine and milnacipran were found to have genotoxic and cytotoxic effects in different test systems [51]. Duloxetine ranks first for hyponatremia, severe skin reactions and life-threatening liver injury [52], but citalopram or escitalopram ranks first for cardiovascular complications.…”