The Effect of Mirtazapine on Cisplatin‐Induced Oxidative Damage and Infertility in Rat Ovaries

Abstract

Cisplatin causes infertility due to ovarian toxicity. The toxicity mechanism is unknown, but evidence suggests oxidative stress. In this study, the effect of mirtazapine on cisplatin-induced infertility and oxidative stress in rats was investigated. 64 female rats were divided into 4 groups of 16. Except for the controls that received physiologic saline only, all were administered with cisplatin (5 mg/kg i.p.) and mirtazapine (15 mg/kg p.o.) or mirtazapine (30 mg/kg p.o.) for 10 days. After this period, six rats from each group were randomly selected, and malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NO), total gluthatione (tGSH), gluthatione peroxidase (GPx), superoxide dismutase (SOD), and 8-hydroxy-2 deoxyguanine (8-OH Gua) levels were measured in their ovarian tissues. Reproductive functions of the remaining rats were examined for 6 months. The MDA, MPO, NO groups and 8-OH Gua levels were higher in the cisplatin-treated groups than the controls, which was not observed in the mirtazapine and cisplatin groups. GSH, GPx, and SOD levels were reduced by cisplatin, which was prevented by mirtazapine. Cisplatin caused infertility by 70%. The infertility rates were, respectively, 40% and 10% for the 15 and 30 mg/kg mirtazapine administered groups. In conclusion, oxidative stress induced by cisplatin in the rat ovary tissue causes infertility in the female rats. Mirtazapine reverses this in a dose-dependent manner.

The Role of Antioxidant Activity in the Prevention and Treatment of Infertility Caused by Cisplatin in Rats

“…In our study, cisplatin-caused oxidative damage was found to be associated with an increase in ovarian tissue MDA levels and a decrease in ovarian tissue tGSH, GSHRd, and GST levels. Similar to our results, Altuner et al [24] found increased oxidative stress and decreased levels of antioxidants in rats that received cisplatin. They also reported that infertility develops in association with this ovarian oxidative damage and this damage-related infertility is prevented with mirtazapine.…”

“…Various reasons such as ischemia reperfusion injury and using chemotherapeutic agents may lead to oxidative ovarian damage [22,23,24,25]. Studies demonstrated an increase in oxidant parameters and a decrease in antioxidant levels in ovarian tissue with oxidative damage in comparison with healthy tissues [22,23,24,25].…”

“…Studies demonstrated an increase in oxidant parameters and a decrease in antioxidant levels in ovarian tissue with oxidative damage in comparison with healthy tissues [22,23,24,25]. The antioxidant defense system in the human body includes enzymatic (GSHRd, GST, etc.)…”

The Effect of Controlled Reperfusion in the Prevention of Infertility Caused by Ischemia Induced in the Contralateral Ovary in Rats with Unilateral Ovariectomy

“…The oxidative stress caused by ovarian I/R injury has been reported to lead to sterility in rats [13]. Altuner et al [24] reported that sterility developed in cisplatin-related oxidative ovarian damage and that antioxidant activity was important in preventing this sterility with mirtazapine. However, although melatonin exhibits more powerful antioxidant activity than thiamine pyrophosphate, it is reportedly ineffective in preventing sterility caused by post-ischemia reperfusion [13].…”

Protective effect of bilberry (Vaccinium myrtillus L.) on cisplatin induced ovarian damage in rat

“…Oxidative stress induced by CDDP in the rat ovary tissue causes infertility in female rats. Mirtazapine reverses this in a dose-dependent manner (Altuner et al 2013). Sharma and Goyal (2012) demonstrated the protective effects of Heliotropium eichwaldi against CDDP-induced nephrotoxicity in mice.…”