The effect of mirtazapine on methotrexate-induced oxidative damage and infertility in rats

Methotrexate (MTX) is a folic acid antagonist and common chemotherapeutic drug. This study investigated the effectiveness of mirtazapine in preventing infertility developed by MTX-associated oxidative damage. In addition, we demonstrate an association between oxidative stress in ovarian tissue induced by MTX and infertility. Rats were divided into three groups: MTX control, mirtazapine + MTX, and healthy control. At the end of the procedures the reproductive function was noted and ovaries extracted to determine malondialdehyde (MDA), myeloperoxidase (MPO), and total glutathione (GSH) levels. MDA concentration in ovarian tissue in the control group given MTX was 13.7 +/- 2.1 mu mol/g protein. In the mirtazapine + MTX group and healthy control group the levels were 7.5 +/- 1.9 and 4.0 +/- 1.4 mu mol/g protein, respectively. MPO activity in the control group given MTX, mirtazapine + MTX, and healthy control groups was 17.8 +/- 4.7, 7.5 +/- 2.4, and 5.2 +/- 1.7 mu mol/g protein, and GSH levels 4.5 +/- 2.1, 11.8 +/- 3.9, and 14.7 +/- 4.7 nmol/g protein, respectively. The study also demonstrated an association between oxidative stress induced by MTX in ovarian tissue and infertility. The mirtazapine used prevented MTX-associated infertility. There were no live births in the control group given MTX alone. However, only one of the 10 rats kept for reproduction did not give birth in the mirtazapine + MTX (end of the procedure only given mirtazapine) group. In conclusion, mirtazapine can be used to prevent infertility appearing in patients receiving MTX therapy.