Sister chromatid exchanges produced by imipramine and desipramine in mouse bone marrow cells treated in vivo

Paniagua-Pérez, Rogelio; Madrigal-Bujaidar, Eduardo; Reyes, Candice; Pérez, G.; Velasco, M.O.; Molina, David A. Castillo

doi:10.1016/s0378-4274(02)00057-7

Cited by 14 publications

(16 citation statements)

References 28 publications

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“…Moreover, with respect to antidepressants, previous reports by our laboratory as well as by other authors have shown positive results, and duloxetine in particular has been reported to induce embryotoxicity in aquatic organisms. 13,14,17,18) Regarding duloxetine, researchers report having examined mouse blood and brain cells with the comet assay and observed negative results. 9) This finding is contrary to our present results and could be related with the different endpoint measured and the applied test, or because DNA ob- servations were made 24 h after duloxetine withdrawal, a time when DNA repair or the detoxification process could have been started.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Duloxetine as Micronuclei Inducer in an Acute and a Subchronic Assay in Mouse

Madrigal-Bujaidar

Álvarez-González

Morales-González

2015

Biological & Pharmaceutical Bulletin

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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.

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Section: Discussionmentioning

confidence: 99%

“…Desipramine was selected because of its high genotoxic capacity previously demonstrated in similar in vivo assays. 13,14) Doses were selected after preliminary assays to avoid systemic toxicity. The low dose corresponded to the recommended therapeutic range for humans.…”

Section: )mentioning

confidence: 99%

Evaluation of Duloxetine as Micronuclei Inducer in an Acute and a Subchronic Assay in Mouse

Madrigal-Bujaidar

Álvarez-González

Morales-González

2015

Biological & Pharmaceutical Bulletin

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“…In another report, 24) authors studied the effect of amitriptyline and imipramine and found that both drugs were moderate SCE inducers in cultured human lymphocytes, although amitriptyline required higher concentrations to show the effect; besides, both antidepressants showed no alterations in the mitotic index. In another research, Paniagua-Pérez et al 13) evaluated the genotoxicity of imipramine and desipramine in mouse bone marrow, and demonstrated a SCE dose-dependent increase with the two drugs, no effect in proliferation kinetics, and a weak mitotic decrease with the highest dose. Furthermore, in mouse bone marrow it was also reported that fluoxetine induced a duplication of SCE in comparison with the control level, no alteration in the cellular proliferation kinetics, and a weak decrease of the mitotic index with the highest tested dose.…”

Section: Discussionmentioning

confidence: 99%

“…12,13) For this purpose we put 1 mL of bisbenzimide 0.001 M made in distilled water on the slides (Höechst solution), expanded it with a coverslip, and kept the slides in the dark for 30 min, then, we added the buffer of differentiation constituted by trisodium citrate plus monobasic, monohydrated sodium phosphate, at pH 7, and we exposed the slides to black light for 90 min. They were then immersed in distilled water, the coverslips detached, and slides were dried at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Genotoxic Evaluation of Duloxetine II. The Effect on the Number of Sister Chromatid Exchanges, the Mitotic Index, and the Proliferation Kinetics in Mouse Bone Marrow

Madrigal-Bujaidar

Álvarez-González

Morales-González

et al. 2017

Biological & Pharmaceutical Bulletin

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Duloxetine is an antidepressant which has showed valuable results, particularly in patients with major depression. This type of drugs is known to require genotoxic studies as part of their preclinical safety evaluation. In the case of duloxetine, however, there have been controversial results. Therefore, we considered it worthwhile to extend studies on the matter in an attempt to reach a conclusion. The present assay was made in mouse bone marrow to evaluate the capacity of the drug to induce sister chromatid exchanges (SCE), as well as to modify the proliferation kinetics and the mitotic index. Three doses of the antidepressant were tested (2, 20, and 200 mg/kg), besides the control mice were administered with purified water, and the positive treated animals administered with 1 mg/kg of doxorubicin. The results indicated a moderate but significant increase of SCE with the three tested doses, no effect regarding the mitotic index and a small reduction in the proliferation kinetics. Although in our assay the drug showed a lower effect, the present study agreed with a previous report that analyzed the amount of micronuclei in mouse peripheral blood, and it confirmed the relevance of evaluating the genotoxic effect of antidepressants, specifically duloxetine by applying diverse tests.

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“…Escuela Nacional de Ciencias Biologicas, IPN, Mexico 2 Escuela Superior de Medicina IPN, Mexico effect since the first week of the treatment. 13,14 To further evaluate the genotoxic potential of these agents, and the type of DNA lesions that they may cause, we determined in this report their capacity to induce structural chromosomal aberrations in mouse.…”

Section: Introductionmentioning

confidence: 99%

Chromosomal aberrations induced by imipramine and desipramine in mouse

Madrigal-Bujaidar¹,

García²,

Álvarez-González³

2010

Hum Exp Toxicol

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Imipramine (IMI) and desipramine (DES) are two drugs widely used for the treatment of depression as well as for other diseases. In the present study, we determined their capacity to induce chromosomal aberrations in mouse bone marrow cells. Three doses of each compound were tested and their results were compared with the frequency of chromosomal aberrations obtained in a control group as well as with a group treated with cyclophosphamide. Our results showed a significant increase in chromosome damage with the doses tested for each compound: 7, 20, and 60 mg/kg in the case of IMI, and 2, 20, and 60 mg/kg as regards DES. This last drug induced stronger chromosomal damage than IMI. Our results agree with previous studies regarding the induction of micronuclei and sister chromatid exchanges by the drugs in mouse and suggest caution with respect to their use in long-term treatments.

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Sister chromatid exchanges produced by imipramine and desipramine in mouse bone marrow cells treated in vivo

Cited by 14 publications

References 28 publications

Evaluation of Duloxetine as Micronuclei Inducer in an Acute and a Subchronic Assay in Mouse

Evaluation of Duloxetine as Micronuclei Inducer in an Acute and a Subchronic Assay in Mouse

Genotoxic Evaluation of Duloxetine II. The Effect on the Number of Sister Chromatid Exchanges, the Mitotic Index, and the Proliferation Kinetics in Mouse Bone Marrow

Chromosomal aberrations induced by imipramine and desipramine in mouse

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