TY - JOUR
T1 - 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
AU - Madrigal-Bujaidar, Eduardo
AU - Álvarez-González, Isela
AU - Madrigal-Santillán, Eduardo Osiris
AU - Morales-González, José A.
AU - Torres-Gómez, Andrea
AU - Cristóbal-Luna, José Melesio
N1 - Publisher Copyright:
© 2017 The Pharmaceutical Society of Japan.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Antidepressant
KW - Duloxetine
KW - Mouse
KW - Sister chromatid exchange
UR - http://www.scopus.com/inward/record.url?scp=85030753036&partnerID=8YFLogxK
U2 - 10.1248/bpb.b17-00260
DO - 10.1248/bpb.b17-00260
M3 - Artículo
C2 - 28966254
SN - 0918-6158
VL - 40
SP - 1796
EP - 1800
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
IS - 10
ER -