Evaluation of the protective effects in ovarian developing follicles of acetyl L-carnitine on experimental cisplatin gonadotoxicity

Chemotherapy is one of the main therapy procedures in cancer treatment. However, chemotherapeutic agents cause certain toxic effects in the long term. One of these toxic effects is gonadotoxicity. The ovaries are particularly sensitive to chemotherapy. Reproductive problems such as premature ovarian failure occur as a result of chemotherapy. Cisplatin is one of the most commonly used chemotherapeutic agents in cancer therapy, but it has certain serious side effects as nephrotoxicity and ototoxicity. Besides, other known gonadotoxic effects are granulose cell and primordial follicle damage. Alternative therapy methods such as oocyte and embryo cryopreservation have been developed to prevent toxic effects of chemotherapy. Among these alternative methods is the use of antioxidant agents and they can prevent the damage by free radicals. This study aims to investigate the toxic effect of cisplatin, which causes the formation of free oxygen radicals, on ovaries and possible preservative function of acetyl L-carnitine, an antioxidant agent. Rats used in these experiments were divided into four groups as the control group, acetyl L-carnitine group, cisplatin group, and acetyl L-carnitine+cisplatin group. The tissues removed after the treatments were evaluated by applying morphometric and immunohistochemical methods. Although the evaluation revealed weight loss in cisplatin and cisplatin+acetyl L-carnitine groups, it was greater in the cisplatin group. A significant reduction in primordial follicles was observed in the cisplatin group when compared with other groups. It was seen in immunohistochemical studies that primordial and primer follicles in the cisplatin group did not show BMP-6 expression. It was also seen that connexin 43 protein expression was reduced in granulose cells and p34cdcc2 expression was reduced in oocytes in the cisplatin group. In addition, the reduction in the cisplatin group was evidence for the toxic effects of cisplatin. The expression of these three proteins and primordial follicle numbers in cisplatin+ acetyl L-carnitine group were higher than those in the cisplatin group, which suggests that acetyl L-carnitine has protective effects.