Reproductive Toxicology 43 (2014) 85–93 Contents lists available at ScienceDirect Reproductive Toxicology jo ur nal homep age: www.elsevier.com/locate/reprotox Sodium selenite treatment restores long-lasting ovarian damage induced by irradiation in rats: Impact on oxidative stress and apoptosis Riham Soliman Said a , Amira Mohamed Badr b , Ahmed Shafik Nada a , Ebtehal El-Demerdash b,∗ a National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt b Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt a r t i c l e i n f o Article history: Received 18 May 2013 Received in revised form 12 November 2013 Accepted 19 November 2013 Available online 27 November 2013 Keywords: Selenite Irradiation Folliculogenesis Proliferation Oxidative stress Apoptosis a b s t r a c t The deleterious damage of reproductive function following radiotherapy is of increasing importance. In the present study, we investigated the impact of long-term sodium selenite (SS) treatment on radiotherapy-induced ovarian injury in a rat model. Two-week after radiation exposure vaginal cyclicity was arrested, and serum FSH level was elevated in irradiated female rats. SS significantly ameliorated ovarian and uterine oxidative stress induced by irradiation through decreasing the lipid peroxide level and increasing the glutathione level, and glutathione peroxidase activity. In the presence of SS, ovar- ian cytochrome c and caspase 3 expressions triggered by radiotherapy were decreased. SS significantly counteracted radiation-induced a widespread loss of ovarian follicles and caused further stimulation of follicular proliferation through enhancing PCNA expression. Despite such alteration in ovarian function, serum estradiol level did not change after irradiation, whereas SS significantly increased it. In conclusion, long-term SS treatment improved reproductive development, which was impaired by radiotherapy. © 2013 Elsevier Inc. All rights reserved. 1. Introduction During the normal reproductive lifespan of females, 300–500 mature oocytes will be ovulated and the vast majority of fol- licles (over 99%) are lost by a process of atresia, which occurs throughout folliculogenesis as well as from the primordial pool. The non-renewable nature of the oocyte pool makes it so vulner- able. Therefore, one of the important health problems for young women is exposure to external agents such as radiotherapy that contribute to accelerating oocyte depletion and premature onset of menopause [1]. Over the last decades, great attempts have been made to minimize the toxic effects of radiotherapy on the ovaries and to reduce the well-known risk of premature ovarian failure (POF) and infertility [2]. Wallace et al. [3] estimated the dosage at which half of the follicles are lost in humans (LD 50 ) to be 4 Gy. It is important to mention that gastrointestinal malignancies and anal carcinoma patient received median radiation dose range from 45 to ∗ Corresponding author at: Department of Pharmacology and Toxicology Faculty of Pharmacy, Ain Shams University, Abasia, Cairo, Egypt. Tel.: +20 2 24729767; mobile: +20 1001925375. E-mail addresses: ebtehal dm@yahoo.com, ebtehal dm@pharma.asu.edu.eg (E. El-Demerdash). 56 Gy using fraction doses of 1.8–2 Gy, twice daily [4,5]. Recently, rapid ovarian dysfunction has been observed in young females after initiation of cancer radiotherapy treatment [6]. POF is character- ized by ovary dysfunction, decreased the number of the growing ovarian follicles, increased concentrations of gonadotropins, and reduced concentrations of ovarian steroids [7]. Besides, it was declared that radiation prior to puberty has been associated with irreversible damage to the uterus, with prepubertal uterine mor- phology observed in post-pubertal patients [8]. The deleterious effects of ionizing radiation on biological sys- tems are mainly mediated through the generation of reactive oxygen species (ROS) in cells as a result of water radiolysis [9]. Low levels of ROS are important signal in regulation of physio- logical functions in female reproduction, including folliculogenesis, steroidogenesis, corpus luteum function, and luteolysis [10]. How- ever, increasing ROS production has a key role in pathological processes in female reproduction [11,12]. Additionally, apoptosis is an essential component of ovarian function and development, which is responsible for oocyte loss [1,13], and it can be further induced by radiation [14]. Selenium (Se), an essential trace element, protects cells from oxidative stress by expression of selenoprotein genes and through anti-inflammatory mechanisms [15]. Low Se states have been asso- ciated with reproductive dysfunctions [16] leading to degeneration 0890-6238/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.reprotox.2013.11.005