The effect of favipiravir and dexamethasone alone and combined on ovary tissue and reproductive function in rats. Biochemical and histopatological evaluation

Objective: COVID-19 disease, caused by a new type of coronavirus, emerged in December 2019 and affected the whole world. There is currently no specific and proven treatment method for COVID-19. Treatment protocols have been updated since the beginning of the epidemic, according to studies. Favipiravir, an RNA polymerase inhibitor, has been used in the treatment of COVID-19 patients in our country in May 2020. Dexamethasone can also be added to the treatment for COVID-19 patients receiving oxygen supplementation or ventilator support. Apart from the reported side effects of these drugs, the potential for adverse effects belonging to different systems may exist and should be monitored. Its effects, especially on the female reproductive system, are unknown. In our study, we aimed to evaluate the biochemical and histopathological effects of favipiravir and dexamethasone alone or in combination on ovarian tissue and reproductive function in female rats. Material and Methods: In this prospective study, 32 female albino wistar rats were used and the rats were divided into four groups of eight. The rats in the first group were not administered any drugs (control group-SG). SG group was given the same volume of distilled water as the solvent in the other group. To the second group, favipiravir was administered orally to the stomach at a dose of 100 mg/kg (FPR). The third group was given dexamethasone 8 mg/kg i.p. routed injected (DEKSA). Finally, favipiravir (100 mg/kg) + dexamethasone (8 mg/kg) combined was administered to the fourth group by the same route (FDA). This procedure was repeated for a week. During the experiment, estrus phases were followed by taking a smear once every day. At the end of this period, the animals were anesthetized and blood samples (~2 cc) were taken from the heart and serum AMH levels were measured. Then, the ovarian tissues of the animals killed by decapitation were removed and MDA and tGSH measurements were made. Again, histopathological damage detection and follicle count in the ovarian tissue were investigated with a light microscope. Results: When the AMH measurements of the groups in our study were examined, it was seen that they were similar in the SG and DEKSA groups, and were at a lower level in the FPR and FDA groups compared to the SG, but this difference was not found to be significant. When the tissue MDA level was examined in terms of oxidative stress, it was observed that it was similar in the SG and DEKSA groups, approximately twice the SG in the FPR group, and approximately 6 times the SG in the FDA group. Tissue MDA elevation in the FPR and FDA groups was found to be significant compared to the SG and DEKSA XII groups, while the tissue MDA elevation in the FDA group was found to be significant compared to the FPR group. When tGSH levels were compared between the groups in terms of antioxidant activity, it was observed that the levels were close to each other in the SG and DEKSA groups, but were significantly lower in the FPR and FDA groups. Again, the amount of tGSH in the FDA group was found to be significantly lower than the FPR group. When the number of primordial follicles was compared in the groups, the number of follicles that were lower in the FPR and DEKSA groups compared to SG was not statistically significant, while a significantly lower number of follicles was found in the FDA group compared to SG. Conclusions: It has been shown in vivo that favipiravir and/or dexamethasone may adversely affect ovarian reserve by decreasing the serum AMH level and the number of ovarian primordial follicles, and may cause oxidative stress by increasing the amount of oxidant reagents in the ovarian tissue and decreasing the amount of antioxidant reagents. Both the COVID-19 disease and the drugs used in its treatment can affect different systems in the reproductive system. As our study is valuable in this respect, there is a need for many studies investigating side effects, adverse effects and drug interactions.