title: 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.
authors.affiliation: Cell Biology Department, National Research Center, Giza, Egypt. hmsaber@yahoo.com
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Hassanane
authors.forename: Naglaa
authors.initials: N
authors.lastname: Hafiz
authors.forename: Walaa
authors.initials: W
authors.lastname: Radwan
authors.forename: Akmal A
authors.initials: AA
authors.lastname: El-Ghor
mesh_terms: D000639:Amitriptyline / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000473:pathology; D002869:Chromosome Aberrations / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D008297:Male; D008540:Meiosis / Q000187:drug effects; D051379:Mice; D008940:Mitotic Index; D009152:Mutagenicity Tests; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity; D013076:Sperm Count; D013090:Spermatocytes / Q000187:drug effects* / Q000473:pathology; D013094:Spermatozoa / Q000002:abnormalities / Q000187:drug effects
chemical_list: D000929:Antidepressive Agents, Tricyclic; D009153:Mutagens; D000639:Amitriptyline