Toxicity and Anti-Inflammatory Effects of Agave sisalana Extract Derived from Agroindustrial Residue.

BACKGROUND: In several countries, the leaf juice of Agave sisalana (also known as sisal) is widely used topically, especially as an antiseptic, and orally for the treatment of different pathologies. However, in Brazil, which is the largest producer of Agave sisalana, its residue, which represents the majority of its weight, has been thrown away. For this reason, the determination of the pharmacological and toxicological potentials of sisal residue and its possible therapeutic use is seen as a way to contribute to the sustainable development and social promotion of the largest producer of sisal in Brazil, the interior of Bahia State, which is among the poorest areas in the country. Given the scarcity of available scientific studies on the pharmacological and toxicological properties of sisal residue juice, this study aimed to promote the acid hydrolysis of this juice to potentiate the anti-inflammatory effect already described in the literature. Furthermore, it aimed to evaluate the toxicological profile of the hydrolyzed extract (EAH) and to determine its acute toxicity, as well as its side effects on the reproductive aspects of rats. METHOD: The anti-inflammatory effect of EAH was evaluated in vitro using the induction of hemolysis by hypotonic solution and in vivo in rats using the carrageenan-induced paw edema test and the xylene-induced ear edema test. The acute toxicity, resulting from a single-dose administration, was investigated for some manifestation of toxic symptoms related to motor control and consciousness in rats. At a concentration of 100 mg/kg, by repeated doses, the reproductive toxicity effects of EAH in rats were assessed. RESULTS: In vitro anti-inflammatory activity was positive using the human red blood cell membrane stabilization method. In both in vivo tests used to assess the anti-inflammatory activity, EAH (at three doses) significantly inhibited edema when compared to the control group. At a dose of 50 mg/kg, EAH exhibited a greater effect than indomethacin, a nonsteroidal anti-inflammatory drug with known activity. In vivo toxicological studies have shown that EAH does not present toxic effects when administered orally in a single dose, up to 1000 mg/kg. Finally, EAH promoted a gonadotoxic effect and increased the embryonic mortality rate after implantation. CONCLUSIONS: It is suggested that the anti-edematogenic effect of the acid hydrolysis extract from sisal juice is due to the high concentration of steroidal sapogenins. Therefore, this extract can be considered a potential new anti-inflammatory or even an important sapogenin source for the development of steroidal glucocorticoids. However, further studies are needed to elucidate the chemical composition of sisal juice. Regarding toxicology studies, EAH did not show cytotoxic and clastogenic potentials, but it presented a powerful reproductive toxic effect in rats.

Toxicological, genotoxic and antioxidant potential of pyrostegia venusta / Potencial toxicológico, genotóxico e antioxidante de Pyrostegia venusta

Pyrostegia venusta is usually found in the secondary growth of the Atlantic forests, and in the Brazilian Savanna. Flowers and leaves of this plant are used in folk remedies for treating a wide variety of healthy conditions, this way is important evaluate its safety and antioxidant potential for this applications. For this, was made a ethanolic extract from its flowers and analyzed with toxicological,genotoxicity and antioxidant tests, the toxicological analysis was made by reproductive toxicity in rats and clatogenicity/aneugenicity in human lymphocytes. The genotoxicity was studied by micronucleus test mice bone marrow. The antimutagenic test in root cells of Allium cepa, the antioxidant assays used was DPPH, FRAP, Lipid Perxidation and REM, beyond of that the extract was analyzed in HPLC showing the profile of its compounds. The toxicological analysis showed that P. venusta has no negative significant effect on reproductive and cellular level. The micronucleus test in mouse bone marrow, the extract protected cells from cyclophosphamide, mutagenic compound, in a similar way. The A. cepa test showed that the extract reduced chromosomal disorders formations. The antioxidant activity of extract was significant, except in REM test. The phytochemical analysis showed the presence of flavonoids compounds. P. venusta extract does not present reproductive toxicity and genotoxic effects. However, the extract of this species showed antigenotoxic and antioxidant potential, possibly due to the different flavonoid compounds present in its extract.

Pyrostegia venusta é geralmente encontrada no crescimento secundário das florestas atlânticas e na savana brasileira. Flores e folhas desta planta são utilizadas em remédios populares para tratar uma grande variedade de doenças, desta forma é importante avaliar a segurança e o potencial antioxidante para estas aplicações. Para tanto, o extrato etanólico das flores foi avaliado com testes toxicológicos, genotóxicos e antioxidants. A análise toxicológica foi realizada por meio da toxicidade reprodutiva em ratos e a clatogenicidade/aneugenicidade em linfócitos humanos, a genotoxicidade foi estudada por teste de micronúcleo em medula óssea de camundongo. A antimutagenicidade em células da raiz de Allium cepa. Os ensaios antioxidantes utilizados foram DPPH, FRAP, TARBS e MRE. O extrato foi analisado em HPLC. A análise toxicológica reprodutiva mostrou que P. venusta não tem efeito negativo sobre o nível reprodutivo e cellular. No teste do micronúcleo o extrato protegeu as células da ciclofosfamida, um composto mutagênico. O teste de A. cepa mostrou que o extrato reduziu as formações dos distúrbios cromossômicos. A atividade antioxidante do extrato foi significativa, exceto no teste REM. A análise fitoquímica mostrou a presença de compostos flavonoídicos. O extrato de P. venusta não apresenta toxicidade reprodutiva e efeitos genotóxicos. No entanto, o extrato desta espécie apresentou potencial antigenotóxico e antioxidante, possivelmente devido aos diferentes compostos flavonoídicos presentes em seu extrato.

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.

Histomorphometrical evaluation in testis and epididymis of rats with pulmonary emphysema experimentally induced by prolonged exposure to cigarette smoke / Avaliação histomorfométrica em testículo e epidídimo de ratos com enfisema pulmonar induzido experimentalmente por exposição prolongada à fumaça de cigarro

The study evaluated the histomorphometrical aspects of testis and epididymis of adult rats with pulmonary emphysema experimentally induced by exposure to cigarette smoke for 30 weeks. Previous studies related to effects of the cigarette smoke on male reproductive tissue were performed in relatively shorter time periods and thus, it does not allow a direct correlation between smoke exposure and damage to reproductive structures like testis and epididymis. In order to evaluate the effect of cigarette smoke for long period on the testis and epididymis, twelve adult Wistar rats were divided into two groups: Control (CG; exposed to ambient air) and Smoking (SG; exposed to cigarette smoke). The weight of the testes, epididymides, seminal glands and prostate were not affected (p>0.05) by experimental treatment. In the SG, the testes presented cellular desquamation, significant decrease in the number of germ cells and Sertoli cell, and reduction (p<0.05) in area and diameter of seminiferous tubules. The exposure of animals to cigarette smoke did not promoted histological changes in the epididymis, but decreased significantly the ductular area and epithelial height in the caput and corpus regions. It was concluded that testis was more susceptible than the epididymis to the effects of cigarette smoke constituents in rats with pulmonary emphysema experimentally induced by prolonged cigarette-smoke exposure.

O estudo avaliou os aspectos histomorfométricos dos testículos e epidídimos de ratos adultos induzidos experimentalmente ao enfisema pulmonar por exposição à fumaça de cigarro, durante 30 semanas. Estudos prévios relacionados aos efeitos da fumaça de cigarro sobre o aparelho reprodutor masculino foram realizados com tempos de exposição relativamente curtos e, dessa forma, não permitem estabelecer uma correlação direta entre exposição à fumaça e danos às estruturas reprodutoras, como testículo e epidídimo. Buscando, portanto, avaliar o efeito da fumaça de cigarro sobre os testículos e epidídimos de animais expostos por longos períodos à fumaça de cigarro, doze ratos albinos da linhagem Wistar foram divididos em dois grupos: Controle (GC; expostos ao ar ambiente) e Tabagista (GT; expostos à fumaça de cigarro). Os pesos dos testículos, epidídimos, glândulas seminais e próstata não foram afetados (p>0,05) pelo tratamento experimental. No GT, os testículos apresentaram descamação celular, diminuição significativa no número de células germinativas e células de Sertoli, além de uma redução (p<0,05) na área e diâmetro dos túbulos seminíferos. A exposição dos animais à fumaça de cigarro não promoveu alterações histológicas nos epidídimos, mas diminuiu significativamente a área ductular e a altura epitelial nas regiões de cabeça e cauda. Concluiu-se que os testículos foram mais susceptíveis do que os epidídimos aos efeitos dos constituintes da fumaça de cigarro em ratos induzidos experimentalmente ao enfisema pulmonar.

Effects of different doses of nandrolone decanoate on estrous cycle and ovarian tissue of rats after treatment and recovery periods.

This study tested the hypothesis that different doses of nandrolone decanoate (ND) will cause changes in the estrous cycle and ovarian tissue of adult rats; and investigated the duration of the recovery period that is sufficient to restore the damage in the animals treated with different doses. Wistar rats were treated with ND at doses of 1.87, 3.75, 7.5 and 15 mg/kg body weight, or received mineral oil (control group) for 15 days, subcutaneously. All animals were divided into three groups according to the treatment periods: (i) ND treatment for 15 days; (ii) ND treatment followed by a 30-day recovery; and (iii) ND treatment followed by a 60-day recovery. Estrous cycle was monitored daily, and at the end of each period, the animals were euthanized for histopathological analysis. During ND treatment and after 30-day recovery, all animals exhibited persistent diestrus. After a 60-day recovery, persistent diestrus was only maintained in the group that had received the highest dose. Ovarian weight was decreased significantly after the 30-day recovery, regardless of ND doses, compared with the control group. There was a reduction (P < 0.05) in the number of corpora lutea and antral and growing follicles, in contrast to an increase (P < 0.05) in atretic follicles in a dose- and time-dependent manner. Remarkable histopathological changes occurred in the ovaries of all ND-treated groups. In conclusion, the different doses of ND caused changes in the estrous cycle and ovarian tissue of rats, and recovery periods (30 and 60 days) were insufficient to completely restore the damage in the animals treated with the highest dose.

Evaluation of testicular tissue of adult rats treated with cisplatin incorporated into the liposome.

Cisplatin (CPL) is one of the most widely used and effective chemotherapeutic agents for the treatment of several human malignancies. However, it causes serious side effects, especially on reproduction. In order to reduce the undesirable effects caused by many drugs, liposomes have been used as a good system for drug delivery. The aim of this study was to investigate, for the first time, the effects of CPL incorporated into the dipalmitoyl phosphatidylcholine liposome (DPPC) on the testicular tissue of adult Wistar rats. The animals (n = 20) were distributed into four experimental groups: (a) control (distillated water); (b) liposome (DPPC, 1 mL), (c) cisplatin incorporated into liposome (CPL/DPPC), and (d) CPL (8 mg/kg body weight). The animals received a single intraperitoneal injection and were killed 10 days after each treatment for histopathological analysis of testes. The results showed that the testicular histomorphometric parameters in rats of DPPC and CPL/DPPC groups were similar to those of the control group. Meanwhile, rats of the CPL-treated group showed a variety of morphological alterations, including atrophy of seminiferous tubules and presence of multinucleated cells in the germinal epithelium. The incorporation of CPL into the liposome had no influence on the testicular weight or any other stereological parameters, but it was beneficial in maintaining the body weight of the animals. In conclusion, the liposome suppressed the cytotoxic effects caused by cisplatin in the testes of rats, suggesting a possible use in chemotherapy against cancer to reduce the side effects seen on reproduction.

Platelet-rich plasma (PRP): methodological aspects and clinical applications.

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.

Dose-dependent effects and reversibility of the injuries caused by nandrolone decanoate in uterine tissue and fertility of rats.

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.

Histopathologycal findings in the ovaries and uterus of albino female rats promoted by co-administration of synthetic steroids and nicotine.

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; 7.5mg/kg BW/week); testosterone mixture (T; 7.5mg/kg BW/week); nicotine (N; 2.0mg/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.

Administração experimental de esteróide anabólico androgênico e álcool causa alterações histológicas e morfométricas nos ovários e útero de ratas adultas / Experimental administration of anabolic androgenic steroid and alcohol causes histological and morphometrical alterations in the ovaries and uterus of adult rats

O uso abusivo e indiscriminado de esteróides anabólicos androgênicos é uma prática comum entre jovens e adultos de ambos os sexos. Geralmente estas substâncias são utilizadas simultaneamente com outras drogas, lícitas ou não, que causam prejuízos à saúde. O objetivo do estudo foi avaliar a influência da administração experimental do esteróide decanoato de nandrolona (DN), associado ou não ao álcool, nos ovários e útero de ratas adultas. Fêmeas com ciclo estral regular (n = 20), foram distribuídas nos grupos: a) controle (solução fisiológica); b) DN (7,5 mg/kg de peso corpóreo; intraperitoneal); c) álcool (AL; 0,2 mL/100g de peso corpóreo; oral); d) DN + AL. Os tratamentos foram realizados através de uma única dose por semana, durante doze semanas consecutivas. Verificou-se que os tratamentos experimentais promoveram alterações no ciclo sexual, na histologia ovariana e uterina, na quantificação folicular e nos parâmetros morfométricos do útero, sendo estes efeitos marcantes nos grupos androgenizados DN e DN + AL. Concluiuse que o uso isolado ou simultâneo de esteróide anabólico e álcool promovem toxicidade ovariana e uterina em ratas adultas.

Nandrolone decanoate and physical effort: histological and morphometrical assessment in adult rat uterus.

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.

[Effects of androgenic anabolic steroids on the uterus and reproductive parameters of adult female rats]. / Efeitos dos esteroides anabólicos androgênicos sobre o útero e parâmetros reprodutivos de ratas adultas.

PURPOSE: to evaluate the effects of the administration of two synthetic steroids in the uterus morphology and in the reproductive parameters of adult female rats. METHODS: 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). RESULTS: 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. CONCLUSIONS: steroidal agents alter the uterine structure and impair fertility and gestational outcome in female rats.

Efeitos dos esteroides anabólicos androgênicos sobre o útero e parâmetros reprodutivos de ratas adultas / Effects of androgenic anabolic steroids on the uterus and reproductive parameters of adult female rats

OBJETIVO: avaliar os efeitos da administração de dois esteroides sintéticos sobre a morfologia do útero e parâmetros reprodutivos de ratas adultas. MÉTODOS: quarenta ratas foram aleatoriamente distribuídas nos grupos experimentais: controle (C; solução fisiológica); tratados com decanoato de nandrolona (DN; 7,5 mg/kg de peso corpóreo); composto de ésteres de testosterona (T; 7,5 mg/kg de peso corpóreo); e, simultaneamente, com DN e T (7,5 mg/kg de peso corpóreo de cada esteroide), em uma única dose/semana, intraperitoneal, durante oito semanas. Cinco fêmeas de cada grupo foram sacrificadas e os cornos uterinos foram coletados, pesados e preparados para avaliação histológica e morfométrica. As ratas restantes foram acasaladas com machos normais para avaliação dos parâmetros reprodutivos, constituindo os grupos tratados durante o período pré-gestacional. Outro grupo de 20 ratas recebeu os tratamentos durante o período gestacional (7º-14º dias). Foi aplicada a análise de variância não paramétrica de Kruskal-Wallis, complementada com o teste de Dunn ou de Student-Newman-Kleus para análise dos dados (5 por cento de significância). RESULTADOS: houve aumento significativo no peso corpóreo das fêmeas androgenizadas (DN: 305±50; T: 280±35; DN+T: 275±30 versus C: 255±22 g) (p<0,05). O peso uterino não foi afetado pelos tratamentos esteroidais (DN: 0,6±0,2; T: 0,4±0,04; DN+T: 0,7±0,1 versus C: 0,4±0,09 g). Todas as fêmeas androgenizadas apresentaram aciclicidade estral e endométrio caracterizado pelo revestimento luminal papilífero, estroma edematoso com áreas hemorrágicas e atividade secretora. Houve alterações nos parâmetros morfométricos de espessura do epitélio luminal, miométrio e perimétrio, em função do grupo androgenizado. Nenhuma rata exibiu prenhez quando tratada com os esteroides no período pré-gestacional, e o tratamento durante a organogênese afetou negativamente os parâmetros reprodutivos. CONCLUSÕES: os agentes esteroidais alteram ...

PURPOSE: to evaluate the effects of the administration of two synthetic steroids in the uterus morphology and in the reproductive parameters of adult female rats. METHODS: 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 percent significance level). RESULTS: 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. CONCLUSIONS: steroidal agents alter the uterine structure and impair fertility and gestational outcome in female rats.

Morfometria e estereologia testicular de ratos adultos tratados com ciclofosfamida incorporada ao lipossoma / Testicular morphometry and stereology of adult rats treated with cyclophosphamide incorporated to the liposome

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.

Histological assessment of ovaries and uterus of rats subjected to nandrolone decanoate treatment.

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.

Morphological evaluation of the testes in adult guinea pigs (Cavia porcellus, L) treated with oxamniquine incorporated into synthetic phospholipid (dimyristoil phosphatidylcholine) vesicles

The aim of this study was to examine the effects of the potent schistosomicide oxamniquine on the testicular morphology of adult guinea pigs following incorporation of the drug int synthetic phospholipid-DMPC vesicles. The guinea pigs were allocated to one of four groups: a) controls (no vesicles or oxamniquine), b) vesicle-treated controls which received DMPC (80 mM), c) treatment with oxamniquine (15 mg/kg) incorporated into DMPC, and d) treatment with oxamniquine diluted in mineral oil. Morphological evaluation showed that the testicular structure in the groups treated with DMPC vesicles and with oxamniquine incorporated into DMPC was similar to the control group. However, guinea pigs that received only oxaminiquine had testes with a variety of morphological alterations. These findings indicate that when oxamniquine was administered alone it caused testicular damage, but when incorporated into synthetic phospholipidic vesicles, the side effects were suppressed.