title: Mirtazapine protects against cisplatin-induced oxidative stress and DNA damage in the rat brain.
abstract: OBJECTIVE
  Cisplatin chemotherapy is associated with neurotoxicity, and oxidative stress might play an important role in the pathogenesis. Mirtazapine may be a preventative agent via its less-known antioxidant properties. The aim of this study was to examine the potential chemoprotective effects of mirtazapine against cisplatin-induced oxidative stress and DNA damage.
  
  
  METHODS
  Twenty-four rats were divided equally into four groups: control; cisplatin (10 mg/kg i.p.); cisplatin plus mirtazapine (10-30 mg/kg, respectively i.p and p.o.); and mirtazapine (30 mg/kg p.o.). The rats were killed at the end of the 14th day of treatment. Brain tissue was examined with regard to antioxidant/oxidant biochemical parameters.
  
  
  RESULTS
  Although glutathione (tGSH) and nitric oxide (NO) end product mean scores were found to be statistically higher in the control group when compared with the cisplatin group (72.44% and 61.99% percentage change [PC], respectively), malondialdehyde (MDA), myeloperoxidase (MPO), and 8-hydroxyguanine (8-OH-GUA) mean scores were statistically lower in the control group in comparison with the cisplatin group (-55.48%, -67.99%, and -48.81% PC, respectively; P < 0.01). Finally, tGSH and NO end product levels were restored to normal (85.90% and 55.30% PC, respectively), and MDA, MPO, and 8-OH-GUA were significantly reduced by treatment with mirtazapine (-60.50%, -78.59%, and -38.10% PC, respectively; P < 0.01).
  
  
  CONCLUSIONS
  Mirtazapine has chemoprotective effects against cisplatin-induced oxidative stress and DNA damage in the rat brain, which may be attributed to its antioxidant capabilities. It would be useful to investigate whether cisplatin at the desired doses can be given concurrently with mirtazapine.
authors.affiliation: Department of Psychiatry, Ataturk University Medical Faculty, Erzurum, Turkey. mustafagulec78@yahoo.com
authors.forename: Mustafa
authors.initials: M
authors.lastname: Gulec
authors.forename: Elif
authors.initials: E
authors.lastname: Oral
authors.forename: Onur B
authors.initials: OB
authors.lastname: Dursun
authors.forename: Atakan
authors.initials: A
authors.lastname: Yucel
authors.forename: Ahmet
authors.initials: A
authors.lastname: Hacimuftuoglu
authors.forename: Fatih
authors.initials: F
authors.lastname: Akcay
authors.forename: Halis
authors.initials: H
authors.lastname: Suleyman
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000078785:Mirtazapine; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D008803:Mianserin; D009569:Nitric Oxide; D008315:Malondialdehyde; C024829:8-hydroxyguanine; D006147:Guanine; D000078785:Mirtazapine; D009195:Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D002945:Cisplatin