Immunohistochemical evaluation of cell proliferation and apoptosis markers in ovarian surface epithelial cells of cladribine-treated rats

Abstract

Cladribine has been used in the treatment of hairy cell leukemia for about 30 years. In addition, the number of indications for the application of 2-CdA is constantly increasing. The treatment with cladribine, of younger persons and even children, appears to be a major factor stimulating the more exact recognition of its activities. However, till now, little has been known about the impact of cladribine on the reproductive system. The aim of the study was to evaluate the immunohistochemical expression of cell proliferation and apoptosis markers in ovarian surface epithelial (OSE) cells. In our study, ten rats were placed into two equal groups. The study group received daily subcutaneous injections of cladribine in a dose of 0.10 mg/kg of weight/day for one cycle lasting 7 days. The control group received only saline injections. The rats were sacrificed 24 h after the last injection, and their ovaries were extracted. The sections were immunohistochemically stained with cell proliferation marker Ki-67 and the apoptosis marker caspase 3. The expressions of the markers were evaluated using a light microscope. An analysis was made using an image analysis system and the CellAD software. The results were then statistically explored by way of the Mann–Whitney U test. The proliferative index (Ki-67) of ovarian surface epithelial cells was significantly lower in the study group than in the control group (p < 0.05). These results suggest that cladribine treatment has a potential to inhibit the OSE cell proliferation in rats. The apoptosis marker demonstrated a significant increase after the cladribine treatment. These suggest that cladribine induces apoptosis in OSE cells.