Efeito do extrato seco da Dioscorea villosa e do fitoestrógeno diosgenina em modelo experimental de artrite induzida por zimosan em camundongos ovariectomizadas

Abstract

Although female reproductive aging (ERF) is intrinsic to women's lives, it is only from the twentieth century that its management is based on evidence. Especially, regarding its relationship with impacts in health and other health problems during the stages of transitioning from menopause to post-menopause. Thus, among conditions related to the ERF, both rheumatoid arthritis and osteoarthritis are prevalent and its relationship with the decline in estrogen (E) concentrations are evidenced in literature. Although hormone replacement therapy (HRT) is not officially used in the treatment of arthritis, studies have shown its effectiveness. However, it is worth mentioning that the use of HRT has increased the incidence of diseases such as breast cancer, thromboembolism and heart attack. On this account, natural products called phytoestrogens have shown to be promising therapeutic alternatives, for its safer use due to its greater selectivity for E. receptors. Still, for these compounds to become a safe and effective therapy, is necessary further clinical and non-clinical studies. In light of this, the present work aims to investigate the effect of the dry extract of Dioscorea villosa (DV) and its phytoestrogen Diosgenin (DSG), in an experimental model of zymosan (Zim) induced arthritis in mice, previously afflicted by induced post-menopause caused by oophorectomy. For that purpose, the female Swiss mice were submitted to bilateral ovariectomy (OVX). After surgical recovery, the animals were divided into experimental groups (n = 7) and their respective pretreatments started for 20 days. The control groups received different vehicles: 2% tween 80, v.o and sesame oil, s.c. Treatment groups received different doses of DV (1, 10 and 100 mg / kg, v.o), DSG (1, 5 and 50) mg / kg, s.c.), indomethacin (5mg / kg, sc) and HRT with 17 ßestradiol (50 μg / kg, sc). On the twentieth day of treatment, arthritis was induced with i.a injection of Zim in the femur-tibial joint in positive control and treatment groups, with the exception of the negative control group, which received only i.a injection of saline. After 4h, the animals were anesthetized while their blood and i.a lavage were collected for total and differential leukocyte count. In addition, histological joint slices were prepared and in parallel, the uterus mass, the estrous cycle and the vaginal size were observed in these animals. The results were analyzed by ANOVA followed by the Tukey’s post-test (p ≤ 0.05). The test groups treated with DV and DSG showed a decrease in neutrophils migration to the joint (9.28 ± 2.26, 10.36 ± 3.95, 9.9 ± 4.55 neutrophil x 104 / articular cavity e 12.16 ± 4.52, 4.92 ± 1.48 e 4.74 ± 2.54 neutrophil x 104/ articular cavity) compared to positive control group (26.5 ± 2.34 neutrophil x 104/ articular cavity). In regard to the leukocytes number in blood, only the group treated with 50 mg / kg of DSG showed increase in total leukocytes number compared to control group. Regarding the reproductive tract of OVX females, only the groups treated with DSG had an increase of the uterus mass, changes in the estrous cycle to the proestro and estro phases and an increase in vaginal size similar to the group of animals pre-treated with HRT. Hence, it is concluded that both pretreatments are effective in reducing the inflammatory parameters of Zim-induced arthritis in female OVX mice. Nevertheless, it is significant that the groups which received the highest dose of DSG showed changes in the reproductive tract. While all doses of DV dry extract, as well as lower doses of DSG were considered effective, but also safe for acting exclusively in inflammatory centers.