The electron and light microscopic evaluation of effects of the Lapatinib on rat ovary and uterus

As a result of the important developments in molecular oncology, many drugs on the agenda started to be use in targeted anti-cancer treatment interrupt proliferation of tumor cells via interacting with cell receptors and intracellular signaling molecules. The objectives of this kind of treatments have physiological functions however it has been reported that a variety of adverse effects can be develop during the use of some targeted drugs. Lapatinib is one of the drugs which is used in targeted therapies, enters into the cell and inhibits the activity of epidermal growth factor and receptor-linked tyrosine kinase. Many mammalian uterine and ovarian tissues have EGFR and HER2 which influence uterine activity, oocyte maturation and follicular development. Our study aimed to investigate changes on uterine and ovarian tissues of rats may cause by Lapatinib on biochemical, light and electron microscopic levels.24 female Wistar rats were divided into 3 groups, respectively we applied 30 mg/kg and 75 mg/kg Lapatinib to the experimental groups and the same amount of distilled water was given to the control group twice a day dose by gavage during the 14 days. Intracardiac blood samples were taken from the rats under anesthesia for biochemical analysis, uterine and ovarian tissue samples were taken for light and electron microscopic examination at the end of the experiment. FSH, LH, estrogen and progesterone levels in blood serum were measured via E170 İmmunoassay method as well as sections from the tissues which were prepared accordance to the methods of light and electron microscopy were examined by Jeol 1400 TEM and Olimpus BX50 light microscope.Beside the reduction of estradiol and progesterone levels in the rats of experimental groups, it was observed that there were structural changes in stromal cells and glands of endometrium, oocyte, granulose cells and interstitial cells of ovaries and it was pointed out that these changes were more prominent in the high dose group.In conclusion, depending on blockage of receptors and signal molecules are targeted by drugs which are used to targeted therapies such as Lapatinib which can cause structural and functional changes of tissues and organs.Key Words: Ovary, Uterus, Lapatinib, Ultrastructure.