Evaluation of Duloxetine as Micronuclei Inducer in an Acute and a Subchronic Assay in Mouse
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- Madrigal-Bujaidar Eduardo
- Laboratorio de Genética. Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional
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- Álvarez-González Isela
- Laboratorio de Genética. Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional
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- Madrigal-Santillán Eduardo Osiris
- Laboratorio Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional
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- Morales-González José A
- Laboratorio Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional
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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.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 38 (8), 1245-1249, 2015
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679608842240
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- NII論文ID
- 130005090646
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 026617381
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- PubMed
- 26235590
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 使用不可