Abstract

We evaluated the duloxetine DNA damaging capacity utilizing the comet assay applied to mouse brain and liver cells, as well as its DNA, lipid, protein, and nitric oxide oxidative potential in the same cells. A kinetic time/dose strategy showed the effect of 2, 20, and 200 mg/kg of the drug administered intraperitoneally once in comparison with a control and a methyl methanesulfonate group. Each parameter was evaluated at 3, 9, 15, and 21 h postadministration in five mice per group, except for the DNA oxidation that was examined only at 9 h postadministration. Results showed a significant DNA damage mainly at 9 h postexposure in both organs. In the brain, with 20 and 200 mg/kg we found 50 and 80% increase over the control group (p ≤ 0.05), in the liver, the increase of 2, 20, and 200 mg/kg of duloxetine was 50, 80, and 135% in comparison with the control level (p ≤ 0.05). DNA, lipid, protein and nitric oxide oxidation increase was also observed in both organs. Our data established the DNA damaging capacity of duloxetine even with a dose from the therapeutic range (2 mg/kg), and suggest that this effect can be related with its oxidative potential.

Details

Title
Genotoxic and oxidative effect of duloxetine on mouse brain and liver tissues
Author
Álvarez-González Isela 1 ; Camacho-Cantera Scarlett 1 ; Gómez-González, Patricia 1 ; Barrón Michael J Rendón 1 ; Morales-González, José A 2 ; Madrigal-Santillán, Eduardo O 2 ; Paniagua-Pérez Rogelio 3 ; Madrigal-Bujaidar Eduardo 1 

 Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Laboratorio de Genética, Ciudad de México, México (GRID:grid.418275.d) (ISNI:0000 0001 2165 8782) 
 Instituto Politécnico Nacional, Escuela Superior de Medicina, Laboratorio de Medicina de La Conservación, Ciudad de México, México (GRID:grid.418275.d) (ISNI:0000 0001 2165 8782) 
 Instituto Nacional de Rehabilitación, Servicio de Bioquímica, Ciudad de México, México (GRID:grid.419223.f) (ISNI:0000 0004 0633 2911) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2505252271
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.