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1.
J Neuroendocrinol ; 31(12): e12816, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31758603

RESUMO

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.


Assuntos
Aromatase/biossíntese , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Receptores Androgênicos/biossíntese , Receptores de Estrogênio/biossíntese , Animais , Relação Dose-Resposta a Droga , Feminino , Hipotálamo/metabolismo , Lactação , Masculino , Hipófise/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos
2.
J Med Food ; 22(4): 393-407, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30990753

RESUMO

Although leaves of Anchietea salutaris are used in Brazilian traditional medicine, there is no available data in the literature proving its efficacy and safety. Thus, the aim of the study was to perform a meticulous botanical, phytochemical, toxicological, and pharmacological investigation of A. salutaris in Wistar rats. At first, a morphoanatomical characterization of Anchietea pyrifolia leaves and stems was performed. Then, a purified infusion (ethanol-soluble fraction obtained from A. pyrifolia [ESAP]) was obtained followed by its chemical profile elucidation. Furthermore, an acute toxicity test was performed, and the acute and prolonged diuretic and hypotensive effects were also evaluated in Wistar rats. Finally, the vasodilatory responses of ESAP in mesenteric vascular beds were investigated. The main secondary metabolites identified from ESAP were O-glycosylated flavonoids, chlorogenic acids, and phenylpropanoic acid derivatives. ESAP did not promote any toxic effects in female rats nor increased urinary excretion in male rats after a single exposure. However, ESAP significantly reduced renal elimination of sodium, potassium, and chloride after prolonged treatment. An ESAP highest dose promoted significant acute hypotension without affecting blood pressure levels after prolonged use. Furthermore, its cardiovascular effects seem to be related with the calcium-activated potassium channel activation in resistance vessels.


Assuntos
Anti-Hipertensivos/administração & dosagem , Hipertensão/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Violaceae/química , Animais , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/química , Pressão Sanguínea/efeitos dos fármacos , Brasil , Diuréticos/administração & dosagem , Diuréticos/efeitos adversos , Diuréticos/química , Feminino , Humanos , Hipertensão/genética , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química , Folhas de Planta/química , Canais de Potássio Cálcio-Ativados/genética , Canais de Potássio Cálcio-Ativados/metabolismo , Ratos Wistar
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