title: Venlafaxine protects against stress-induced oxidative DNA damage in hippocampus during antidepressant testing in mice.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, College of Medicine, Assiut University, Assiut, Egypt. basel_post@msn.com
authors.forename: Basel A
authors.initials: BA
authors.lastname: Abdel-Wahab
authors.forename: Ragaa H
authors.initials: RH
authors.lastname: Salama
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003511:Cyclohexanols / Q000494:pharmacology* / Q000627:therapeutic use; D004249:DNA Damage / Q000187:drug effects* / Q000502:physiology; D003863:Depression / Q000378:metabolism / Q000517:prevention & control; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011897:Random Allocation; D013315:Stress, Psychological / Q000378:metabolism / Q000517:prevention & control*; D000069470:Venlafaxine Hydrochloride
chemical_list: D000928:Antidepressive Agents; D003511:Cyclohexanols; D000069470:Venlafaxine Hydrochloride