Venlafaxine protects against stress-induced oxidative DNA damage in hippocampus during antidepressant testing in mice
Abstract
Unlabelled Venlafaxine (VLF) is an approved antidepressant that is claimed to have superior clinical efficacy to comparable drugs. Recently, many studies showed the relationship between depression and increased oxidative stress. This study investigated the relationship between the antidepressant effect of VLF and its ability to protect animals against stress-induced oxidative lipid peroxidation and DNA damage induced during antidepressant testing.Methods The antidepressant effect of long-term treatment (21 days) of VLF in doses 5, 10 and 20mg/kg/day, i.p. was tested using forced swimming test (FST) and tail suspension test (TST). The effects of VLF on hippocampal lipid peroxidation (MDA), nitric oxide (NO), glutathione (GSH), total antioxidant (TAC) levels and glutathione-S-transferase (GST) activity were tested. Furthermore, the corresponding changes in serum and hippocampal 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured.Results Long-term VLF treatment showed a significant, antidepressant effect in both FST and TST. VLF could decrease the hippocampal MDA and NO and to increase hippocampal GSH and TAC levels and GST activity in the tested animals. Only GSH and TAC levels were increased by VLF in the non-tested animals. In addition, both serum and hippocampal 8-OHdG levels were significantly reduced by VLF in animals exposed to antidepressant tests.Conclusion Long-term VLF treatment in the effective antidepressant doses can protect against stress-induced oxidative cellular and DNA damage. This action may be through antagonizing the oxidative stress and enhancing the antioxidant defense mechanisms. Consequently, pharmacological modulation of stress-induced oxidative DNA damage as a possible stress-management approach should be an important avenue of further research.
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Long-term venlafaxine treatment at effective antidepressant dosages can protect against stress-induced oxidative cellular and DNA damage in male mice.
“Abdel-Wahab and Salama (2011) showed that long-term venlafaxine treatment at effective antidepressant dosages can protect against stress-induced oxidative cellular and DNA damage in male mice.”
From Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder (2012) · cites this paper as [26]
Venlafaxine decreases MDA and total nitrite levels, increases total antioxidant potential and GSH content, and restores GST activity in hippocampus of stressed animals.
“At all doses tested, venlafaxine decreased MDA and total nitrite levels, increased total antioxidant potential and GSH content, and restored GST activity in hippocampus of stressed animals.”
From Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder (2012) · cites this paper as [26]
Venlafaxine increases total antioxidant potential and GSH levels in the control, nonstressed group.
“Venlafaxine also promoted increased total antioxidant potential and GSH levels in the control, nonstressed group.”
From Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder (2012) · cites this paper as [26]
Venlafaxine reduces serum and hippocampal levels of 8-OHdG in stressed animals.
“Finally, this treatment was able to reduce serum and hippocampal levels of 8-OHdG (a marker of DNA damage) in stressed animals [26]”
From Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder (2012) · cites this paper as [26]
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- Authors
- Abdel-Wahab, B. A., & Salama, R. H.
- Affiliations
- Assiut University (EG)
- Venue
- Pharmacology Biochemistry and Behavior
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 100
- Issue
- 1
- Pages
- 59-65
- ISSN
- 0091-3057 (ISSN-L)
- OpenAlex
- W2007039285
- Cited by
- 86
- References
- 64
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 4 · 2023: 4 · 2022: 7 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 4 · 2017: 6 · 2016: 7 · 2015: 12 · 2014: 11 · 2013: 5 · 2012: 7
- FWCI
- 5.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacology Biochemistry and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- venlafaxine, antidepressant effects, oxidative DNA damage, hippocampus, oxidative stress, lipid peroxidation, 8-hydroxy-2'-deoxyguanosine, glutathione, antioxidant defense, nitric oxide, forced swim test, tail suspension test, depression
- MeSH terms
- Venlafaxine Hydrochloride, Animals, Antidepressive Agents, Cyclohexanols, Depression, DNA Damage, Hippocampus, Male, Random Allocation, Stress, Psychological, Oxidative Stress, Mice
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