Effects of diisopentyl phthalate exposure during gestation and lactation on hormone-dependent behaviours and hormone receptor expression in rats.

Phthalates are found in different plastic materials, such as packaging, toys and medical devices. Some of these compounds are endocrine disruptors, comprising substances that are able to induce multiple hormonal disturbances and downstream developmental effects, including the disruption of androgen-dependent differentiation of the male reproductive tract and changes in pathways that regulate hormone-dependent behaviours. In a previous study, metabolites of diisopentyl phthalate (DiPeP), a potent anti-androgenic phthalate, were found in the urine of Brazilian pregnant women. Therefore, the present study aimed to evaluate the effects of DiPeP exposure during critical developmental periods on behaviours controlled by sex hormones in rats. Pregnant Wistar rats were treated with DiPeP (1, 10 or 100 mg kg day-1 ) or canola oil by oral gavage between gestational day 10 and post-natal day (PND) 21. Male offspring were tested in a behavioural battery, including the elevated plus maze task, play behaviour, partner preference and sexual behaviour. After the behavioural tests, the hypothalamus and pituitary of these animals were removed on PND 60-65 and PND 145-160 to quantify gene expression for aromatase, androgen receptor (Ar) and oestrogen receptors α (Esr1) and ß (Esr2). Male rats exposed to 1 and 10 mg kg day-1 DiPeP displayed no preference for the female stimulus rat in the partner preference test and 1 mg kg day-1 DiPeP rats also showed a significant increase in mount and penetration latencies when mated with receptive females. A decrease in pituitary Esr1 expression was observed in all DiPeP treated groups regardless of age. A reduction in hypothalamic Esr1 expression in rats exposed to 10 mg kg day-1 DiPeP was also observed. No significant changes were found with respect to Ar, Esr2 and aromatase expression in the hypothalamus. These results suggest that DiPeP exposure during critical windows of development in rats may induce changes in behaviours related to mating and the sexual motivation of males.

Assessment of the analgesic dipyrone as a possible (anti)androgenic endocrine disruptor.

Mild analgesics have been associated with antiandrogenic effects, but there are no such studies on dipyrone, despite its high prevalence of use in many countries. We examined the production of steroid hormones in human H295R cells after exposure to dipyrone and two metabolites, 4-Methylaminoantipyrine (MAA) and 4-Aminoantipyrine (AA), as well as fetal testicular testosterone production in rats following maternal dipyrone exposure. Androgen agonistic/antagonistic effects were examined in vitro for dipyrone and its metabolites in the Yeast Androgen Screen (YAS) assay and in vivo for dipyrone through the Hershberger assay. In vitro we tested dipyrone, MAA, and AA (0.1-1000 µM) while in vivo we used dipyrone (50, 100, 200 mg/kg/day). In the H295R assay, dipyrone, MAA and AA reduced the production of androgens and corticosteroids. Testosterone was reduced at concentrations 4-13 times higher than the maximum plasma concentrations reported in humans for MAA and AA. No effects were observed in the fetal testosterone production assay. In the YAS and Hershberger assays, no androgen agonistic/antagonistic activities were observed. These results indicate that dipyrone and its metabolites do not interact with the androgen receptor, but have the potential to inhibit steroidogenesis, however only at concentrations that are not relevant under normal medical use.

Risco das plantas medicinais na gestação: uma revisão dos dados de acesso livre em língua portuguesa / Risk of medicinal plants in pregnancy: a review of free access data in portuguese

A gestação é um período único e especial na vida de cada mulher, no qual ocorre uma série de modificações no organismo feminino, tanto do ponto de visto físico como do ponto de vista psíquico, que começam na primeira semana e continuam durante todo o período de gestação. Essas modificações ocasionam uma série de desconfortos (dores musculares, enjoos, vômitos, e constipação) que interferem no estado físico e emocional da gestante. Na busca por aliviá-las muitas gestantes buscam consumir produtos de origem natural por acreditarem que eles não fazem mal. Nessa busca, a crença de que é "natural" é sinônimo de "seguro" tornam o consumo de plantas medicinais atraente para muitas gestantes, que ao consumirem esses produtos, muitas vezes, sem orientação médica ou farmacêutica, acreditam não existir riscos ao embrião/feto e para si mesmas. Isso faz com que o uso medicinal de plantas seja comum na gestação. Porém, existem evidências científicas que muitas substâncias presentes nas plantas medicinais oferecem riscos durante a gestação. Neste contexto, o presente estudo teve por objetivo investigar, por meio de uma revisão de literatura em bases de acesso livre e em língua portuguesa, quais as espécies que podem acarretar algum risco durante a gestação. A literatura disponível para a população em geral evidenciou que diversas espécies são capazes de oferecer risco durante a gestação por apresentarem potencial embriotóxico, teratogênico e abortífero.

Pregnancy is a unique and special time in every woman's life, in which there is a number of physical and psychological changes in the female body, starting from the first week and continuing throughout the entire pregnancy. These changes cause a lot of discomfort (muscle aches, nausea, vomiting, and constipation) interfering in the physical and emotional state of the mother. In the search for relieving such pains, many pregnant women seek to use natural products because of their belief that they do no harm. In this quest, the belief of what is "natural" is a synonym to "safe" make the consumption of such products attractive to many pregnant women, frequently without any medical or pharmaceutical advice, believing there is no risk to the embryo/fetus and for herself. However, there is scientific evidence that many substances in medicinal plants pose risks during pregnancy. In this context, this study aimed to investigate, through a literature review in open access databases and in Portuguese, which species can entail some risk during pregnancy. The literature data available to the general population showed that several species are able to offer risk during the pregnancy because they have embryotoxic, teratogenic and abortive potential.

Atheroprotective effects of Cuphea carthagenensis (Jacq.) J. F. Macbr. in New Zealand rabbits fed with cholesterol-rich diet.

ETHNOPHARMACOLOGICAL RELEVANCE: Although Cuphea carthagenensis (Jacq.) J. F. Macbr. is used in Brazilian folk medicine in the treatment of atherosclerosis and circulatory disorders, no study evaluating these effects has been conducted. The aim of this study was to evaluate the possible hypolipemiant and antiatherogenic activity of the ethanol soluble fraction obtained from C. carthagenensis (ES-CC) in an experimental atherosclerosis model using New Zealand (NZ) rabbits undergoing cholesterol-rich diet (CRD). MATERIAL AND METHODS: Dyslipidemia and atherogenesis were induced by administration of standard commercial diet increased of 1% cholesterol (CRD) for 8 weeks. ES-CC was orally administered at doses of 10, 30 and 100mg/kg, once daily for four weeks, starting from the 4th week of CRD diet. Body weight measurements were weekly carried out from the beginning of experiments for 8 weeks. Serum levels of triglyceride (TG), total cholesterol (TC) and their fractions (LDL-C, VLDL-C and HDL-C) were measured at the beginning of experiments and at weeks four and eight. After euthanasia of rabbits, aorta segments (aortic arc, thoracic, abdominal and iliac segments) were macroscopically and microscopically evaluated and the intima and media layers of the arteries were measured. Additionally, the antioxidant activity of ES-CC and its influence on the functioning of hepatic antioxidant enzymes were also determined. RESULTS: CRD induced dyslipidemia and major structural changes in the aortic wall. In addition, an increase in lipid peroxidation and a reduction of hepatic glutathione and serum nitrite levels were observed. Treatment with ES-CC was able to prevent the increase in TC, LDL-C, VLDL-C levels and triglycerides and promoted an increase in HDL-C levels in NZ rabbits. These effects were accompanied by a significant reduction in oxidative stress and modulation of the catalase and superoxide dismutase function. Moreover, the intima and media layers of the arterial segments were significantly reduced by ES-CC treatment. CONCLUSIONS: This study demonstrated that ES-CC reduces serum lipids and hepatic oxidative stress when orally administered to NZ rabbits. In addition, it was able to prevent the development of CRD-induced atherosclerosis.

Sodium fluoride does not alter sperm production or sperm morphology in rats

The aim of the present study was to evaluate the effects of sodium fluoride (NaF) on the male reproductive system. Adult male rats were exposed to NaF in drinking water for 30 days at three concentrations: 1.54 (control, tap water), 50 and 100 ppm. Body and organ weights, daily sperm production, sperm number and morphology were investigated. No difference was observed on the sperm number and morphology among the groups, as well as body weight and organ absolute and relative weights. Overall, despite the presence of a mild degree of dental fluorosis in the higher dose group, the results indicated that exposure to NaF at the doses used in the present study did not adversely affect sperm production and morphology of male rats.

Screening for in vivo (anti)estrogenic and (anti)androgenic activities of Tropaeolum majus L. and its effect on uterine contractility.

ETHNOPHARMACOLOGICAL RELEVANCE: Tropaeolum majus L. (Tropaeolaceae) is a medicinal herb popularly used in Brazil for treatment of inflammatory and cardiovascular diseases. Despite some published data on its efficacy, there are still few toxicological data describing the safety of this plant. The aim of this study was to evaluate the (anti)estrogenic and (anti)androgenic activity of the hydroethanolic extract obtained from Tropaeolum majus L. (HETM), as well as its possible effects on uterine contractility. MATERIALS AND METHODS: Three experimental protocols were performed, (a) uterotrophic assay, (b) Hershberger assay and (c) an ex vivo test to investigate the effects of maternal administration of HETM on uterine contractility at the end of pregnancy. In all protocols three doses of the HETM were administered to Wistar rats: 3, 30 and 300mg/kg. RESULTS: In vivo tests for detection of (anti)androgenic and (anti)estrogenic activities did not show any significant alterations. Similarly, no alterations were observed on uterine contractility induced by oxytocin and arachidonic acid. CONCLUSIONS: HETM was unable to produce (anti)estrogenic or (anti)androgenic activities in the short-term in vivo screening assays performed. In addition, there was no evidence that HETM can affect uterine contractility following gestational exposure of rats.

Atividade de tropaeolum majus l. sobre a mobilização e migração leucocitária em modelo de bolsão inflamatório / Activity of tropaeolum majus l. on the mobilization and leukocyte migration in an air pouch model

Tropaeolum majus L. (Tropaeolaceae) é uma importante planta medicinal conhecida popularmente no Brasil como chaguinha, capuchinha ou nastúrcio. Toda parte aérea da planta tem sido utilizada há séculos pela medicina popular. Suas folhas secas ou em infusão são usadas popularmente para o tratamento de várias doenças, incluindo processos inflamatórios. O objetivo do presente estudo foi avaliar o perfil da migração leucocitária em vigência de resposta inflamatória aguda, após um tratamento subcrônico com T. majus. Para isto, ratos Wistar machos foram tratados por cinco dias com três diferentes doses do extrato hidroetanólico (EHTM) obtido de T. majus (75, 150 e 300 mg/kg). Os animais controle receberam volume equivalente de solução salina (5,0 ml/kg) ou indometacina (5,0 mg/kg). Durante este período, os animais receberam 10 ml de ar estéril na cavidade subcutânea (air pouch) em três dias alternados. No quinto dia, uma hora após os tratamentos, a resposta inflamatória foi induzida com a administração de 1 ml de carragenina (solução 1%) na cavidade subcutânea, e 6 horas após, amostras de sangue e do exsudato foram coletadas para a determinação de leucócitos totais e para a realização da contagem diferencial. Os resultados demonstraram que a indometacina reduziu o número de leucócitos totais para o exsudato em aproximadamente 65%. O EHTM nas doses de 75 e 300 mg/kg também reduziram significativamente a migração destas células, com valores estimados em 23 e 40%, respectivamente. Estes resultados indicam uma possível atividade anti-inflamatória do T. majus neste modelo experimental, justificando, pelos menos em parte, o uso popular desta espécie.

Tropaeolum majus L. (Tropaeolaceae) is an important medicinal plant popularly known in Brazil as chaguinha, capuchinha or nasturtium. This species has been used for centuries in popular medicine. Dried leaves are popularly used in infusion for the treatment of various diseases, including inflammatory processes. The aim of this study was to assess the profile of leukocyte migration during an acute inflammatory response after a subchronic treatment with T. majus. For this purpose, male Wistar rats were treated for five days with three different doses of hydroalcoholic extract (HETM) obtained from T. majus (75, 150 and 300 mg/kg). Control animals received equivalent volume of saline solution (5.0 ml/kg) or indomethacin (5.0 mg/kg). During this period, the animals received 10 ml of sterile air in the subcutaneous cavity (air pouch) on three alternate days. On the fifth day, one hour after treatment, the inflammatory response was induced by administration of 1 ml carrageenan solution (1%) in the subcutaneous cavity, and 6 hours after, blood and exudate samples were collected for determination of total and differential leukocytes. The results showed that indomethacin reduced leukocyte migration in the exudates to about 65%. The HETM at doses of 75 and 300 mg/kg also significantly reduced the migration of these cells, with values ??of 23 and 40%, respectively. These results indicate a possible anti-inflammatory activity of T. majus in this experimental model, explaining, at least in part, the popular use of this species.

Effects of the Crotalus durissus terrificus snake venom on hepatic metabolism and oxidative stress.

Snake venoms present different action mechanisms because of their complex composition, represented mainly by toxins and enzymes. This work aimed to investigate the effects of the Crotalus durissus terrificus(Cdt) venom in the liver. Wistar rats were inoculated intraperitoneally with saline (control) or Cdt venom. After 3, 4, or 6 h, the following parameters were analyzed: (a) hepatic function, (b) oxidative stress parameters, and (c) the metabolism of alanine in the isolated perfused liver. Plasma activities of alanine aminotransferase and aspartate aminotransferase and hepatic glutathione S-transferase and catalase presented significant elevation in rats inoculated with 300 µg ⋅ kg(-1) Cdt venom. Liver lipoperoxidation was enormously increased by venom doses of 100, 200, and 300 µg ⋅kg(-1) , whereas glutathione S-transferase was not changed. Perfused livers from rats inoculated with 1500 µg ⋅kg(-1) venom showed increased production of lactate, pyruvate, and ammonia when alanine was the metabolic substrate. These results demonstrate that the Cdt venom can produce several changes in hepatocytes. The causes of the changes are possibly related to the disequilibrium in the redox homeostasis but also to specific needs of the poisoned organism, for example, an increased supply of lactate and pyruvate in response to an increased activity of the Cori cycle.

Resíduos de pesticidas em alimentos / Pesticide residues in food

Este trabalho teve como objetivos comparar os níveis de resíduos de pesticidas encontrados em alimentos investigados pelo Programa de Análise de Resíduos de Pesticidas em Alimentos da Agência Nacional de Vigilância Sanitária (PARA/ANVISA) e avaliar o possível risco tóxico da sua ingestão. Para tanto, foram comparados os dados dos relatórios do PARA de 2001 e 2003, quando 2647 amostras de nove culturas de hortaliças e frutas foram analisadas. Calculou-se o risco tóxico da ingestão desses resíduos pela população utilizando dados do limite máximo de resíduo para cada pesticida e do consumo alimentar. Também determinou-se o número de pesticidas que ultrapassaram o limite máximo de resíduos (LMR) permitido e pesticidas encontrados em culturas cujo uso não é permitido. Os resultados indicaram que não houve modificações significativas no número de resíduos encontrados nas duas avaliações efetuadas pelo PARA entre os anos de 2001 e 2003. Dentre as 2.647 amostras analisadas foram detectados resíduos de 2.256 pesticidas, sendo 68 por cento envolvendo o uso regular e 32 por cento o uso irregular (não-autorizado 89 por cento e uso acima do LMR 11 por cento). Dezenove pesticidas apresentaram risco tóxico para a população na avaliação do relatório de 2001 e 16 no relatório de 2003. Esses dados permitem concluir que alimentos com resíduos de pesticidas não deveriam apresentar risco para a população, exigindo melhoria na fiscalização do uso de pesticidas na agricultura.

Screening for in vivo (anti)estrogenic and (anti)androgenic activities of technical and formulated deltamethrin.

Concern over the possibility of hormonal systems being disrupted by chemicals in the environment has led to the development of assays to detect such chemicals. Technical and formulated deltamethrin, a widely used synthetic pyrethroid pesticide, was screened for (anti)estrogenic and (anti)androgenic activities by means of two major in vivo short-term screening tests: the uterotrophic and Hershberger assays. The results reported here indicate the absence of in vivo (anti)estrogenic and (anti)androgenic activities for both technical and formulated deltamethrin at the dose levels tested (2.0 and 4.0 mg/kg/day). However, further tests, including in vitro screening assays, are required to characterize fully the lack of endocrine action of these chemicals.