Investigation of the effects of ferulic acid on apoptosis in A model of premature ovarian failure (POF)

Premature ovarian failure (POF) is the loss of normal ovarian function before the age of 40 and is a condition that affects approximately 1% of women under 40 and 0.1% of women under 30 years of age. It is characterized by insufficient ovarian sex hormones and a decreased number of follicles that precipitate menopause, which often results in infertility. Cyclophosphamide (SF) is a chemotherapeutic agent widely used in the treatment of various types of cancer and has a detrimental effect on the female reproductive organs, especially the ovary. In our study, we aimed to examine the histochemical, immunohistochemical and biochemical effects of Ferulic acid (FA), which is known to have antiapoptotic, antifibrotic and antioxidant properties, in the ovaries of rats for which a POY model was created using SF. In our study, 24 Wistar albino female rats weighing 200-250 g were divided into 4 groups as Control, FA, SF, SF+FA. Vaginal smears were applied to the rats daily. The control group was given 1 mL/kg of intraperitoneal saline on the 1st, 7th and 14th days. Ferulic acid group rats were given 50 mg/kg FA by oral gavage every day for 2 weeks. SF group subjects were administered 75 mg/kg ip cyclophosphamide on the first day of the experiment. Then, on the 7th and 14th days, 1 mL/kg ip serum physiologic was given. SF+FA group subjects were administered 75 mg/kg ip cyclophosphamide on the 1st day of the experiment and 1 mL/kg ip saline was given on the 7th and 14th days. From day 15 to day 30, 50 mg/kg FA was administered by oral gavage every day for 2 weeks. At the end of the experimental period, the subjects were sacrificed. H&E, Masson trichrome and PAS stains for histochemical analysis; For immunohistochemical analyzes, Activated-Caspase-3, Bcl-2, Bax, iNOS, eNOS and PCNA immunostaining were performed. For biochemical analyses, TOS and TAS measurements were made in serum. In the histomorphological examinations, normal ovarian structure was observed in the Control and FA groups, while a decrease in the number of primary and primordial follicles and an increase in the number of atretic follicles were observed in the SF group. An increase in the number of follicles, a decrease in the number of atretic follicles and a morphology close to the control group were observed in the SF+FA group. In immunohistochemical staining, increased activated-caspase-3 and decreased Bcl2/Bax ratios were observed in the SF group. While iNOS decreased in the FA group and increased in the SF group, eNOS decreased in the SF group. The proliferation marker PCNA was decreased in the SF group. All these values were close to the Control group in the SF+FA group. Biochemically, TOS levels increased significantly in the SF group compared to the Control and FA groups, but decreased in the FA group. A significant decrease was observed in the FA treatment compared to the SF group. TAS value increased significantly in the FA group compared to the Control and SF groups. In line with the results we obtained, in ovaries with follicle loss, tissue damage, apoptosis and increase in oxidative stress due to the effect of cyclophosphamide, which is known to have a gonadotoxic effect, FA protects the follicle reserve, reduces tissue damage, has anti-apoptotic and antioxidant properties. It has been shown that it can have positive effects in ovarian failure.