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.

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.

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).

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.