Sci Rep. 2021 Mar 25;11(1):6897. doi: 10.1038/s41598-021-86366-0.
Genotoxic and oxidative effect of duloxetine on mouse brain and liver tissues
Isela Álvarez-González 1, Scarlett Camacho-Cantera 1, Patricia Gómez-González 1, Michael J Rendón Barrón 1, José A Morales-González 2, Eduardo O Madrigal-Santillán 2, Rogelio Paniagua-Pérez 3, Eduardo Madrigal-Bujaidar 4
PMID: 33767322 PMCID: PMC7994804 DOI: 10.1038/s41598-021-86366-0
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.
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Note - Many of us have long wondered about potential brain damage from Cymbalta. Well here is a preliminary report. Most of the results were at levels above normal dosing but some damaging effects were found at therapeutic doses. Would these oxidative effects be reversable, say with the use of antioxidants? Who knows. How is the DNA effected and what are the effects from it? Only the future will tell.
