[Show abstract][Hide abstract] ABSTRACT: The use of anabolic androgenic steroids is often associated with the use of other substances, licit or not, such as nicotine present in the tobacco. The present study investigated for the first time the effects of co-administration of synthetic steroids and nicotine on the ovarian and uterine tissue and fertility of adult female rats. Animals were submitted to treatment groups (n = 16/group): nandrolone decanoate (ND; 7.5 mg/kg BW/week); testosterone mixture (T; 7.5 mg/kg BW/week); nicotine (N; 2.0 mg/kg BW/day), and co-administration of ND/N, T/N and ND/T/N. The control group received saline solution daily. The injections were administered subcutaneously for 30 consecutive days. Results demonstrated that all androgenized rats exhibited estral acyclicity and there was suppression of reproductive capacity due to notable ovarian and uterine histological changes. Treatments promoted decrease (p < 0.05) in the ovarian weight. Uterine weight increased (p < 0.05) in the T and T/N groups, in comparison to control group. ND or T co-administered or not to nicotine promoted intense follicular degeneration, with formation of cysts in the ovaries. High levels of circulating androgens in the ND/T/N group induced the presence of ovarian sex cord-stromal tumors of Sertoli cell pattern. Androgenized females presented endometrial changes characterized by papilliferous or pleated luminal epithelium, oedematous and hemorrhagic stroma and presence of gland cysts. In conclusion, the co-administration of three drugs promoted atypical morphological pattern on the ovaries and uterus of female rats.
Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie 07/2014; · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study is the first to investigate the effects of different doses of nandrolone decanoate (ND) upon uterine tissue and fertility, and if the reproductive alterations can be restored after cessation of the treatment. Wistar female rats were treated with ND at doses of 1.87, 3.75, 7.5, and 15 mg/kg body weight, diluted in vehicle (n = 30/group), or received only mineral oil (control group, n = 45). The animals were divided into three periods of study: ND-treated receiving a daily subcutaneous injection for 15 consecutive days (1), and treatment with ND followed by 30-day recovery (2), and 60-day recovery (3). At the end of each period, five females per group were induced to death to histopathological analysis and the others were allowed to fertility evaluation (at 19th gestational day). Animals that received ND followed by 30-day recovery exhibited persistent diestrous and marked suppression of reproductive capacity. Conversely, after 60-day recovery, only lowest doses females (1.87 and 3.75 mg/kg) exhibited restoration of normal estrous cyclicity. Uterine weights were increased after ND treatment similarly to that of the controls after 60-day recovery. The ND-treated groups showed histopathological changes in the endometrium, myometrium, and perimetrium, and an increase in the thickness of both muscular and serous layers. Notably, the recovery of uterine tissue after ND treatment was dose- and period-dependent. We reported that administration of ND promoted damage in uterine tissue and fertility of rats, and the recovery periods were insufficient to restore all of the side effects caused by ND under a dose-dependent response
Birth Defects Research Part B Developmental and Reproductive Toxicology 04/2014; 101(2). · 1.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract The clinical use of platelet-rich plasma (PRP) is based on the increase in the concentration of growth factors and in the secretion of proteins which are able to maximize the healing process at the cellular level. Since PRP is an autologous biologic material, it involves a minimum risk of immune reactions and transmission of infectious and contagious diseases, and it has been widely used for the recovery of musculoskeletal lesions. Despite the great potential for applicability, the implementation of the therapeutic employment of PRP as a clinical alternative has become difficult, due to the lack of studies related to the standardization of the techniques and/or insufficient description of the adopted procedures. Therefore, it is required establish standard criteria to be followed for obtaining a PRP of high quality, as well as a larger number of studies which should establish the proper concentration of platelets for the different clinical conditions. In this context, the purpose of this review is to discuss some methodological aspects used for achieving the PRP, as well as to discuss the bioactive properties of PRP, and to point out its therapeutic use in different fields of regenerative medicine.
[Show abstract][Hide abstract] ABSTRACT: Epidermal growth factor receptors 2 (Her-2) and 4 (Her-4) are closely associated with ovarian cancer (OC) progression and metastasis, and a more complete understanding of these signaling pathways allow the development of new therapeutic strategies. Melatonin (Mel) is recognized as having several anticancer properties and has been reported to modulate Her-2 system in aggressive tumors. Here, we investigated OC and the role of Mel therapy on the Her-2- and Her-4-signaling pathway related to downstream molecules in an ethanol-preferring rat model. To induce OC, the left ovary was injected directly with a single dose of 100 µg 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in 10 µL of sesame oil under the bursa. Right ovaries were used as sham-surgery controls. After developing OC, half of the animals received i.p. injections of Mel (200 µg/100 g b.w./day) for 60 days. While Mel therapy was unable to reduce Her-4 and phosphoinositide 3-kinase (PI3K) levels, it was able to suppress the OC-related increase in the levels of the Her-2, p38 mitogen-activated protein kinases (p38 MAPK), protein kinase B (phospho-AKT), and mammalian target of rapamycin (mTOR). In addition, Mel significantly attenuated the expression of Her-2, p38 MAPK, and p-AKT, which are involved in OC signaling during ethanol intake. Collectively, our results suggest that Mel attenuates the Her-2-signaling pathway in OC of ethanol-preferring rats, providing an effective contribution for further development of adjuvant therapies.
[Show abstract][Hide abstract] ABSTRACT: Ginkgo biloba and Panax ginseng are plants used in the traditional medicine. The aim of study was to analyse the gonadal histology of the Wistar male and female rats submitted to the treatments with extract of G. biloba (120 mg kg-1) or P. ginseng (200 mg kg-1), and to evaluate the reproductive and fetal parameters of female rats treated with the plants. The control group received physiological solution 0.9%. The treatments were administered by oral gavage, twice/day, during fifteen consecutive days. After this period, male (n=18) and female rats (n=18) were sacrificed and the gonads collected, weighed and processed for microscopic evaluation. Another females (n=18) were matted with not treated males for evaluation of fertility and pregnancy outcome. The results indicated that the male and feminine reproductive organs weight was not affected by treatments. The gonadal structure of male and female rats showed same histologic pattern in the three experimental groups. The pre-gestational treatment with the extracts not promoted alterations in the reproductive performance of dams and in the fetal parameters. It was concluded that the extract of P. ginseng or G. biloba not presented reproductive toxicity in the male and female rats.
Revista Brasileira de Plantas Medicinais 12/2011; 14(1):34-42.
[Show abstract][Hide abstract] ABSTRACT: In the past decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit abuse of these drugs by athletes and non-athletes. Since that AAS can affect the reproductive tract, resulting in reproduction and fertilization damages, the purpose of this study was to investigate the nandrolone decanoate (ND) effects, associated or not with physical effort, on the uterine histomorphometric parameters. Female Wistar rats, sedentary or not, were exposed to treatment with ND by intraperitoneal injection (5 mg/kg/day, once a week) during four consecutive weeks. Control animals, sedentary or not, received vehicle alone (propylene glycol) in the same manner. The physical activity was forced swimming (20 min/day). During the experiment, all animals were monitored by daily vaginal smears. After 30 days of treatment, the females were sacrificed and their uteri collected and examined under light microscopy techniques. The ND-treated females showed estrus acyclicity and decreased thickness of both the epithelium and endometrial stroma. A reduction in the number and size of blood vessels was also found in ND-treated rats submitted to physical effort when compared to ND sedentary rats. ND-treated rats, regardless of exercise, exhibited stromal fibrosis and reduced gland ducts that displayed high mitotic activity. A remarkable widespread presence of leukocytes occurred in rats receiving ND and submitted to exercise. These results suggest that ND associated or not with physical effort causes histomorphometric changes to the rat uterus.
The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology 02/2011; 294(2):335-41. · 1.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: to evaluate the effects of the administration of two synthetic steroids in the uterus morphology and in the reproductive parameters of adult female rats.
divided into four experimental groups: control (C; physiological solution); treated with nandrolone decanoate (DN; 7.5 mg/kg of body weight); with a testosterone esters compound (T; 7.5 mg/kg); and simultaneously with DN and T (7.5 mg/kg of each steroid), in a single intraperitoneal weekly dose, for eight weeks. Five females of each group were sacrificed and the uterine horns were collected, weighted and prepared for histological and morphometrical evaluation. The remaining rats were mated with normal male rats for reproductive parameters evaluation, composing the groups treated during the pre-gestational period. Another group of 20 female rats were treated during the gestational period (7th-14th days). For data analysis, the Kruskal-Wallis non-parametric variance analysis was used, followed by the test of Dunn or of Student-Newman-Keus (5% significance level).
there was a significant body weight increase in the androgenized females (ND: 305+/-50; T: 280+/-35; ND+T: 275+/-30 versus C: 255+/-22 g; p<0.05). Uterine weight was not affected by the steroidal treatment (ND: 0.6+/-0.2; T: 0.4+/-0.04; ND+T: 0.7+/-0.1 versus C: 0.4+/-0.09 g). All the androgenized females presented estral acyclicity and endometrium characterized by papilliferous luminal lining, oedematous stroma with hemorrhagic areas and secretory activity. There were changes in the morphometrical thickness parameters of the luminal epithelium, myometrium and perimetrium in the androgenized groups. None of the female rats got pregnant when treated with steroids in the pre-gestational period and the treatment during organogenesis affected negatively the reproductive parameters.
steroidal agents alter the uterine structure and impair fertility and gestational outcome in female rats.
Revista brasileira de ginecologia e obstetrićia: revista da Federação Brasileira das Sociedades de Ginecologia e Obstetrícia 09/2009; 31(9):453-60.
[Show abstract][Hide abstract] ABSTRACT: Liposomes represent a useful drug carrier system which is utilized in clinical studies to act as a non-toxic vehicle, reducing side effects and increasing the efficacy of antitumor agents. The aim of this study is to investigate, by means of morphometric and stereologic parameters, the effects of the cyclophosphamide, incorporated to liposomes, in testis of adult rats. As a result, the incorporation of the oncolytic agent to the liposomes showed, in the first place, increase of the testicular weight and volume, as well as an extension in diameter and area of the seminiferous tubules. For the group treated with cyclophosphamide incorporated to liposomes the differences in testicular and parechyma volumes showed non-significant with respect to the control group. Results indicate that the incorporation of the drug to the liposome reduces side effects on the male gonad. Lipossomas representam um benéfico sistema de transporte de fármacos que é utilizado em estudos clínicos para atuar como um veículo não tóxico, reduzindo os efeitos colaterais e aumentando a eficácia de agentes antitumorais. O objetivo deste estudo é investigar, por meio de parâmetros morfométricos e estereológicos, os efeitos da ciclofosfamida incorporada aos lipossomas, em testículos de ratos adultos. Como resultado, a incorporação do agente oncolítico aos lipossomas mostrou, em primeiro lugar, aumento no peso e volume testicular, assim como aumento no diâmetro e área dos túbulos seminíferos.Para o grupo tratado com ciclofosfamida incorporada aos lipossomas as diferenças nos volumes testicular e do parênquima mostraram-se não significativas em relação ao grupo controle.Os resultados indicam que a incorporação da droga ao lipossoma reduz os efeitos colaterais sobre a gônada masculina.
[Show abstract][Hide abstract] ABSTRACT: This study aimed to analyze the effects of nandrolone decanoate on the ovaries and uterus of adult females rats. This drug was administered intraperitoneally, at one, two and three doses of 3 mg nandrolone decanoate/kg of body weight, respectively, in the first, second and third week of treatment. The females of the control group received a physiological solution. The rats treated with nandrolone decanoate showed estral acyclicity and there was destruction of follicular units and an absence of corpus luteum in the ovaries. In the uterus, the drug promoted morphological alterations, characterized by vacuolated epithelium and endometrial stroma fibrosis. Ovary, uterus and pituitary weights were not affected by the steroid treatment. Nandrolone decanoate affects the sexual cycle and promotes histological alterations in the ovaries and uterus of adult female rats.