N. Debbie Slamon and Vic W. Pentreath
The cytotoxicities of the antidepressants amitriptyline, imipramine (both tricyclic), fluoxetine (a selective serotonin re-uptake inhibitor) and tranylcypromine (a monoamine oxidase inhibitor) were compared in vitro in rat (C6) glioma and human (1321N1) astrocytoma cell lines. Differences in toxicity were determined after acute (24-hour) and chronic (7-day) administration and assessed by using the neutral red uptake (NRU) assay, the MTT assay, increased expression of glial fibrillary acidic protein (GFAp), and reactive morphology criteria. The relative toxicities (EC50 [concentration causing an effect in 50% of cells] value range) were fluoxetine > amitriptyline > imipramine > tranylcypromine for all the tests employed, in both cell lines and at both exposure times. There was a high and significant positive correlation between the different cell types, at both exposure times, with both the NRU and MTT assays. Increases in MTT reduction, NRU, and GFAp expression associated with cell activation were noted in C6 cells after exposure for 24 hours, but decreased after exposure for 7 days. For 1321N1 cells, increases in NRU were only observed after exposure for 24 hours. Reactive-type changes in morphology were seen after exposure to all the antidepressants, in both the C6 and 1321N1 cell lines. The data show that low concentrations of antidepressants induce metabolic changes in the astrocyte cell lines, with some significant differences in the patterns of toxicity of the tested substances.
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