Genotoxic evaluation for the tricyclic antidepressant drug, amitriptyline

Abstract

Tryptizol(®) [amitriptyline HCl (AT); El-Kahira Pharmacological and Chemical Co., Cairo, Egypt], a widely used antidepressant drug in Egypt, was evaluated for its genotoxicity. The evaluation was performed in somatic (bone marrow) and germ (spermatocytes) cells, as well as well as the sperm morphology (i.e., head and tail) and count of the resulting sperm. Three doses were tested (low, medium, and high); they were chosen according to the drug manufacturer. The low-dose group received orally 1 mg/kg body weight (b.w.) daily for a total period of 1 month; the medium-dose group received 1 mg/kg b.w. daily for 15 days and 2 mg/kg b.w. daily for another 15 days; and the high-dose group received 1 mg/kg b.w. daily for 10 days, then 2 mg/kg b.w. daily for another 10 days and, finally, 4 mg/kg b.w. daily for 10 more days. The results showed that AT treatment induced structural and numerical chromosome abnormalities in somatic cells (bone marrow) and germ cells (spermatocytes). Moreover, AT significantly reduced both the mitotic index and meiotic activity after the different treatments used. AT was found to increase significantly the incidence of sperm-cell head and tail abnormalities. The sperm-cell count was also significantly decreased with the 3 doses tested. In general, results of chromosome abnormalities in both somatic and germ cells as well as sperm morphology and count showed that the effect of AT was dose dependent. The results of the current study showed that AT is a genotoxic agent for both somatic and germ cells and should be taken under special precautions and medical supervision.

Effects of antidepressants on parameters, melondiadehyde, and diphenyl-2-picryl-hydrazyl levels in mice spermatozoa

“…Actually, consumption of amitriptyline with vitamin c could improve progressive motility, non-progressive motility, viability and decrease immotile. In agreement with our study, Hassanane and co-workers showed a decrease in sperm concentration as well as an increase in morphological abnormalities in the sperm of amitriptyline-treated mice ( 2 ).…”

“…The group Ι (controls) was treated with distilled water, group ΙΙ received amitriptyline (4 mg/kg) ( 2 ), group ΙΙΙ amitriptyline (4 mg/kg)+vitamin C (10 mg/kg) ( 2 , 16 ), group ΙV venlafaxine (2 mg/kg) ( 5 ), and group V vitamin C (10 mg/kg)+venlafaxine (2 mg/kg) ( 5 , 16 ), to form the gavage. All groups were treated in mouse spermatozoa period (35 days), and after the treatment period, they were killed by the displacement of the neck vertebrae.…”

“…Antidepressant drugs are widely used for the treatment of depression, anxiety-related diseases, and stress ( 1 ). The classification of antidepressant drugs is dependent on the drugs chemical structure and how the drugs function ( 2 ). Accordingly, antidepressant drugs fall into five families namely tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, and atypical antidepressants ( 3 ).…”

Neuronal life or death linked to depression treatment: the interplay between drugs and their stress-related outcomes relate to single or combined drug therapies

“…Moreover, higher concentrations of antidepressants were linked with upregulation of pro-apoptotic caspases-3, 8 and 9 in response to global reactive oxygen species-mediated DNA damage in rat primary blood barrier endothelial cells [19]. Further detailed studies revealed that structural chromosomal abnormalities [20], as well as telomeres shortening, may be involved in antidepressants-induced neurotoxicity [21]. As cited, the data on antidepressant-mediated toxicity is still fragmentary and mostly deals with the effect of monotherapy on stress-related effects.…”

Psychotropic Drugs Levels in Seminal Fluid: A New Therapeutic Drug Monitoring Analysis?

“…Although the hormonal changes and the sexual dysfunction may affect sperm quality, a direct spermicidal activity and other toxic effects of psychotropics have been reported in vitro for several classes, such as antidepressants [selective serotonin inhibitors (SSRIs), tricyclics (TCA), noradrenaline and dopamine reuptake inhibitors (NDRI)] and mood stabilizers (carbamazepine, sodium valproate, lithium) (3,(8)(9)(10)(11). Accordingly, further studies in animals and humans treated with psychotropic drugs reported seminal fluid changes, such as reduced sperm quality or increased DNA alterations (12,13). Hormonal and sexual side effects of psychotropics occur relatively frequently and are directly associated to their mechanism of action, while their potential gonadotoxic effects still remain unclear.…”