title: Evaluation of Duloxetine as Micronuclei Inducer in an Acute and a Subchronic Assay in Mouse.
abstract: Duloxetine is a widely used antidepressant worldwide. In the present report, we evaluated its capacity to induce micronucleated polychromatic erythrocytes (MNPEs) and micronucleated normochromatic erythrocytes (MNNEs) in mice. Two assays were performed, one with a single chemical administration and the other with daily chemical administration. In the first, we administered the antidepressant once to groups of 5 mice by the intragastric (i.g.) route (2, 20, and 200 mg/kg) and performed the analysis at 24, 48, and 72 h postadministration. A control group administered i.g. distilled water was included in the assay, as well as another treated with the micronuclei-inducing chemical daunorubicin (2.5 mg/kg, injected intraperitoneally (i.p.)). In this assay, we found significant damage induced by duloxetine starting from the first time evaluated, showing the highest MNPE increase at the end of the assay. We observed a saturation effect as well, suggested by a decreasing relative efficiency with respect to each tested dose. In a second assay, we administered the antidepressant i.g. every day for 5 weeks (2, 6, and 12 mg/kg), and micronuclei analysis was performed at the end of each week. In this study, we also found a significant increase in both MNPEs and MNNEs which was clear by the second week of administration. Our results suggest that short-term as well as cumulative damage is produced by duloxetine. Thus, confirmation of the observed genotoxic potential in other models seems advisable, as well as caution when prescribing this antidepressant.
authors.affiliation: Laboratorio de Genética. Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Madrigal-Bujaidar
authors.forename: Isela
authors.initials: I
authors.lastname: Álvarez-González
authors.forename: Eduardo Osiris
authors.initials: EO
authors.lastname: Madrigal-Santillán
authors.forename: José A
authors.initials: JA
authors.lastname: Morales-González
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000009:adverse effects*; D001681:Biological Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D000068736:Duloxetine Hydrochloride / Q000009:adverse effects*; D004912:Erythrocytes / Q000187:drug effects*; D008297:Male; D008813:Mice, Inbred ICR; D048629:Micronuclei, Chromosome-Defective; D015162:Micronucleus Tests; D009153:Mutagens
chemical_list: D000928:Antidepressive Agents; D009153:Mutagens; D000068736:Duloxetine Hydrochloride