Effects of gallic acid on ovarium damage experimentally created with cyclophosphamide in rats

Objective: In this study, it was aimed to investigate the prophylactic effects of GA against ovarian damage caused by CP administration in rats by histological and biochemical methods. Methods: For the research, 32 adult female Sprague Dawley rats were randomly divided into 4 equal groups (Control, CP, GA, CP+GA). All subjects were weighed on the 1st and 8th days of the experiment. The Control group received no treatment. The CP group was administered 150 mg/kg intraperitoneal CP on the 7th day of the experiment. The GA group was given 20 mg/kg GA daily via oral gavage for 7 days starting from the 1st day of the experiment. The CP+GA group received 20 mg/kg GA daily via oral gavage for 7 days starting from the 1st day of the experiment and 150 mg/kg intraperitoneal CP on the 7th day. On the 8th day of the experiment, blood samples were collected from the rats, and their ovaries were removed. The right ovary was used for histopathological evaluations, while the left ovary was used for biochemical analyses. Sections were stained with Hematoxylin-Eosin, Masson's Trichrome, Periodic Acid-Schiff, and TUNEL methods. Histopathological evaluations, follicle counting, and scoring were performed. Biochemical analyses included measurements of glutathione peroxidase (GPX), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), tissue anti-Müllerian hormone (AMH), and serum AMH levels. Results: In the CP group, follicular cell degeneration was significantly increased compared to the Control and GA groups. In the CP+GA group, follicular cell degeneration was significantly reduced compared to the CP group but remained higher than in the Control and GA groups. The GA group exhibited a morphology similar to the Control group. In the CP group, anti-Müllerian hormone (AMH) levels were higher compared to the Control and CP+GA groups. The number of primordial follicles was decreased in the CP group compared to the Control and CP+GA groups. The number of unilaminar primary follicles was reduced, and the number of atretic follicles was increased in the CP group compared to the Control and GA groups. In the CP+GA group, the number of unilaminar primary follicles was reduced compared to the Control group, and the number of atretic follicles was higher compared to the Control and GA groups. Malondialdehyde (MDA) levels were higher in the CP group compared to the Control and GA groups. MDA levels were reduced in the CP+GA group compared to the CP group. Superoxide dismutase (SOD) activity was decreased in the CP group compared to the Control, CP+GA, and GA groups. Catalase (CAT) activity was higher in the CP+GA and GA groups compared to the other groups, but was decreased in the CP group compared to the Control group. Tissue AMH values were lower in the CP group compared to the Control group. Serum AMH levels were higher in the GA group compared to the other groups. Conclusions: It was concluded that GA may be effective in preventing follicular cell damage caused by CP in adult rat ovaries. Key Words: Cyclophosphamide, Gallic Acid, Ovary, İnfertility.