Nandrolone decanoate causes uterine injury by changing hormone levels and sex steroid receptors in a dose- and time-dependent manner.

Different doses of nandrolone decanoate (ND) were used to investigate the expression of uterine sex steroid receptors (AR, ER-α, and ER-ß) and the levels of serum sex hormones after treatment and recovery periods in adult rats. ND doses of 1.87, 3.75, 7.5, or 15 mg/kg b.w. or mineral oil (control group) were injected subcutaneously for 15 days, and the experimental groups were divided into three periods of evaluation: (a) ND treatment for 15 days, (b) ND treatment followed by 30-day-recovery and (c) ND treatment followed by 60-day-recovery. Estrous cycle was monitored daily. At the end of each experimental period, rats were euthanized for the collection of serum samples and uterine tissues. All animals showed persistent diestrus and only the highest ND dose was capable of inducing persistent diestrus until 60-day-recovery. Immunoexpression of uterine sex steroid receptors varied in a time-dependent manner. While AR expression was increase after treatment period, ER-α and ER-ß expressions decreased after 60- and 30-day-recovery, respectively. ND also increased the serum levels of testosterone, 17ß-estradiol, and dihydrotestosterone, especially at the highest doses of 7.5 and 15 mg ND/kg until 30 days of recovery. The levels of progesterone were significantly reduced in all ND-treated animals. No significant difference was observed in the levels of follicle-stimulating hormone, whereas the levels of luteinizing hormone varied according to specific dose and period. We conclude that uterine sex steroid receptors and sex hormones are affected by ND administration and these alterations can be only restored following lower doses and long recovery periods.

Analysis of antioxidant, cytotoxic and mutagenic potential of Agave sisalana Perrine extracts using Vero cells, human lymphocytes and mice polychromatic erythrocytes

Brazilian Northeast is the world's largest producer of Agave sisalana Perrine for the supply of the sisal fiber. About 95% of plant biomass, which comprise the mucilage and sisal juice, is considered a waste residual is discarded in the soil. However, the sisal juice is rich in steroidal saponins, which exhibits different pharmacological properties. Despite this, natural products are not necessarily safe. Based on this, this study analyzed the antioxidant, cytotoxic and mutagenic potential of three extracts derived from acid hydrolysis (AHAS), dried precipitate (DPAS) and hexanic of A. sisalana (HAS). These analyses were performed by in vitro and in vivo methods, using Vero cells, human lymphocytes and mice. Results showed that AHAS 50 and 100 can be considered a useful antineoplastic candidate due to their antioxidant and cytotoxic activity, with no genotoxic/clastogenic potential in Vero cells and mice. Although the comet assay in human lymphocytes has showed that the AHAS 25, AHAS 50 and AHAS 100 can lead to DNA breaks, these extracts did not promote DNA damages in mice bone marrow. Considering the different mutagenic responses obtained with the different methods employed, this study suggest that the metabolizing pathways can produce by-products harmful to health. For this reason, it is mandatory to analyze the mutagenic potential by both in vitro and in vivo techniques, using cells derived from different species and origins.

Analysis of antioxidant, cytotoxic and mutagenic potential of Agave sisalana Perrine extracts using Vero cells, human lymphocytes and mice polychromatic erythrocytes

Brazilian Northeast is the world's largest producer of Agave sisalana Perrine for the supply of the sisal fiber. About 95% of plant biomass, which comprise the mucilage and sisal juice, is considered a waste residual is discarded in the soil. However, the sisal juice is rich in steroidal saponins, which exhibits different pharmacological properties. Despite this, natural products are not necessarily safe. Based on this, this study analyzed the antioxidant, cytotoxic and mutagenic potential of three extracts derived from acid hydrolysis (AHAS), dried precipitate (DPAS) and hexanic of A. sisalana (HAS). These analyses were performed by in vitro and in vivo methods, using Vero cells, human lymphocytes and mice. Results showed that AHAS 50 and 100 can be considered a useful antineoplastic candidate due to their antioxidant and cytotoxic activity, with no genotoxic/clastogenic potential in Vero cells and mice. Although the comet assay in human lymphocytes has showed that the AHAS 25, AHAS 50 and AHAS 100 can lead to DNA breaks, these extracts did not promote DNA damages in mice bone marrow. Considering the different mutagenic responses obtained with the different methods employed, this study suggest that the metabolizing pathways can produce by-products harmful to health. For this reason, it is mandatory to analyze the mutagenic potential by both in vitro and in vivo techniques, using cells derived from different species and origins.

Ovarian sex steroid receptors and sex hormones in androgenized rats.

This study evaluated for the first time the effects of different doses of the anabolic steroid nandrolone decanoate (ND) on the expression of ovarian steroid receptors (AR, ER-α (ESR1) and ER-ß (ESR2)) and related sex hormones after treatment and recovery periods in adult rats. The animals were injected subcutaneously with doses of ND (1.87, 3.75, 7.5 or 15 mg/kg b.w.) or mineral oil (control group) for 15 days, and the experimental groups were divided into three periods of evaluation: (a) ND treatment for 15 days, (b) ND treatment and recovery for a period of 30 days and (c) ND treatment and recovery for a period of 60 days. Estrous cycle was monitored daily. At the end of each period, rats were killed for collection of blood and ovaries. Persistent diestrus occurred in all rats during ND treatment and after 30-day recovery. The highest dose of ND was able to maintain all rats arrested at diestrus until 60-day recovery. The expression of steroid receptors varied in a dose- and period-dependent manner, having a more pronounced response with the dose of 15 mg ND/kg. ND treatment increased serum levels of testosterone, 17ß-estradiol and dihydrotestosterone, especially at the highest doses of 7.5 and 15 mg ND/kg. No change was observed in the levels of follicle-stimulating hormone (FSH), whereas levels of the luteinizing hormone (LH) varied according to the dose and period. In conclusion, the ovarian sex steroid receptors and sex hormones were restored only at lower doses of ND and after a longer period of recovery.

Ovarian histology and follicular score in female rats treated with nandrolone decanoate and submitted to physical effort.

The study was conducted to analyze the histology of the ovaries of adults rats treated with steroids, and submitted or not to physical effort. The control group consisted of females submitted to physical effort and sedentary females, both of which received a physiological solution of 0.9% saline. Treated females, sedentary or not, received 6 mg/kg of body weight of nandrolone decanoate. The steroid and physiological solution were administered intraperitoneally, with a single injection per week for 4 consecutive weeks. The applied physical effort was swimming (20 minutes daily, 5 days/week, for the 4 weeks of treatment). Serial sections (5 mum) of ovaries were prepared for histological evaluation and follicular score. The weight of ovaries and hypophysis, the number of antral and atretic follicles, and the area of corpus luteum were all affected by the steroids. In the ovaries of the control groups, well-developed corpus luteum was observed. In the treated groups, the cortical stroma was occupied by ovarian interstitial tissue. The females treated with steroids presented estral acyclicity. The use of nandrolone decanoate, whether associated with physical effort or not, affected the morphological pattern of the ovaries.