TY - JOUR
T1 - Investigation of the DNA Damage and Oxidative Effect Induced by Venlafaxine in Mouse Brain and Liver Cells
AU - Madrigal-Bujaidar, Eduardo
AU - Paniagua-Pérez, Rogelio
AU - Rendón-Barrón, Michael Joshue
AU - Morales-González, José Antonio
AU - Madrigal-Santillán, Eduardo O.
AU - Álvarez-González, Isela
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2022/12
Y1 - 2022/12
N2 - Venlafaxine is an antidepressant used worldwide. Therefore, studies to confirm its safe use are mandatory. This report evaluated the drug DNA damage capacity in the brain and liver of ICR mice, and its oxidative effect on DNA, lipids, and proteins, as well as the amount of nitrites, also in the brain and liver. Determinations were made at 2, 6, 12, and 24 h post-treatment, excluding DNA oxidation that was observed at 2 h. The tested doses of venlafaxine were 5, 50, and 250 mg/kg. The results showed DNA damage in the brain with the two more elevated doses of venlafaxine at 2 and 6 h post-treatment and also at 12 h in the liver. The comet assay plus the FPG enzyme showed DNA damage in both organs with all doses. The two high doses increased lipoperoxidation in the two tissues from 6 to 12 h post-administration. Protein oxidation increased with the three doses, mainly from 2 to 12 h, and nitrite content was elevated only with the high dose in the liver. The drug was found to affect both tissues, although it was more pronounced in the liver. Interestingly, DNA oxidative damage was observed even with a dose that corresponds to the therapeutic range. The clinical relevance of these findings awaits further investigations.
AB - Venlafaxine is an antidepressant used worldwide. Therefore, studies to confirm its safe use are mandatory. This report evaluated the drug DNA damage capacity in the brain and liver of ICR mice, and its oxidative effect on DNA, lipids, and proteins, as well as the amount of nitrites, also in the brain and liver. Determinations were made at 2, 6, 12, and 24 h post-treatment, excluding DNA oxidation that was observed at 2 h. The tested doses of venlafaxine were 5, 50, and 250 mg/kg. The results showed DNA damage in the brain with the two more elevated doses of venlafaxine at 2 and 6 h post-treatment and also at 12 h in the liver. The comet assay plus the FPG enzyme showed DNA damage in both organs with all doses. The two high doses increased lipoperoxidation in the two tissues from 6 to 12 h post-administration. Protein oxidation increased with the three doses, mainly from 2 to 12 h, and nitrite content was elevated only with the high dose in the liver. The drug was found to affect both tissues, although it was more pronounced in the liver. Interestingly, DNA oxidative damage was observed even with a dose that corresponds to the therapeutic range. The clinical relevance of these findings awaits further investigations.
KW - genotoxicity
KW - molecular oxidation
KW - mouse brain and liver
KW - venlafaxine
UR - http://www.scopus.com/inward/record.url?scp=85144673015&partnerID=8YFLogxK
U2 - 10.3390/toxics10120737
DO - 10.3390/toxics10120737
M3 - Artículo
C2 - 36548570
AN - SCOPUS:85144673015
SN - 2305-6304
VL - 10
JO - Toxics
JF - Toxics
IS - 12
M1 - 737
ER -