Micronuclei induced by imipramine and desipramine in mice: a subchronic study.
Depression is a common disease that may cause severe damage to human health. Imipramine (IMI) and desipramine (DES) are medicaments used for treatment, yet studies on their genotoxic potential have given controversial results. Therefore, we designed the present assay to determine their effect as inducers of micronucleated polychromatic erythrocytes (MNPE) and micronucleated normochromatic erythrocytes (MNNE) in mice. The study was carried out in animals administered daily with the compounds for 4 weeks, and the determination of micronuclei was done each week. We also evaluated the bone marrow cytotoxicity induced by the chemicals. Besides, the same determinations were carried out in the following 4 consecutive weeks, but in this period the animals were not treated with the tested compounds. Our results showed a significant increase in both MNPE and MNNE induced by both compounds from the first week of administration. At the fourth week, IMI increased three times the control level, while the effect of DES was about seven times such level. In the second, 4-week phase, we observed a reduction in the rate of micronuclei approaching the control level. We also detected a bone marrow-mitotic division decrease by the evaluated chemicals. Our results point to the need for cautiousness in the clinical use of the compounds as well as for testing the effect in patients under treatment.
Madrigal-Bujaidar
Eduardo
E
Genetics Laboratory, National School of Biological Sciences, IPN, Mexico. eduardo.madrigal@lycos.com
Madrigal-Santillán
Eduardo Osiris
EO
Alvarez-Gonzalez
Isela
I
Baez
Rocio
R
Marquez
Pilar
P
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D003891:Desipramine / Q000633:toxicity; D007099:Imipramine / Q000633:toxicity*; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests; D008938:Mitosis
D000929:Antidepressive Agents, Tricyclic; D007099:Imipramine; D003891:Desipramine