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

Durdu Altuner,Omer Erkan Yapca,Nihal Cetin,Mine Gulaboglu

doi:10.1155/2013/327240

Durdu Altuner, Omer Erkan Yapca + Show 2 more

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https://doi.org/10.1155/2013/327240

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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.

Highlights

Cisplatin, a platinum derivative, is a chemotherapeutic agent used for the treatment of solid tumors [1]
The data obtained in the study demonstrated that cisplatin caused significant oxidative stress in the ovarian tissues of rats
As the results of our study demonstrated, in ovarian tissues of animals administered cisplatin, there was an increase in the levels of MDA and MPO, which are oxidant parameters, while the levels of antioxidants such as tGSH, gluthatione peroxidase (GPx), and superoxide dismutase (SOD) were decreased

Summary

Introduction

A platinum derivative, is a chemotherapeutic agent used for the treatment of solid tumors [1]. Cisplatin is asserted as an intermediately gonadotoxic agent [2]. It has been demonstrated that cisplatin-associated infertility is caused by the toxic effect on the primordial follicles. Since the primordial follicles are not able to regenerate, the damage caused by the exposure to toxic agents may lead to ovarian insufficiency and infertility [3]. The severe adverse effects occurring during cancer chemotherapy restrict the appropriate use of anticancer drugs [4]. The anti-cancer drugs, those used in early childhood and in reproductive period, may cause several complications such as ovarian insufficiency and infertility [5]. In recent years, trials have been initiated on several methods to prevent infertility in patients given chemotherapy [6]

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