RESUMO
Passiflora incarnata is marketed in many countries as a phytomedicine. Even though the directions of most marketed phytomedicines recommend them to be used under medical supervision, reproductive and developmental studies are sparse and not mandatory for regulatory purposes. In this study, a reproductive toxicity evaluation of P. incarnata was conducted in Wistar rats gavaged (30 or 300 mg/kg) during pregnancy and lactation. Moreover, considering that antioxidant properties have been attributed to flavonoids present in the genus Passiflora, it was also evaluated the antioxidant/pro-oxidant balance in the plasma of these dams and the antioxidant potential in an in vitro test. P. incarnata treatment did not influence dams´ body weight as well as reproductive (gestation length, post-implantation loss, litter size, litter weight) and hepatic (albumin, AST, ALT, GGT) parameters. The antioxidant property of P. incarnata was evidenced both in vivo (increase in the total antioxidant plasmatic potential) and in vitro (decrease in neutrophil-induced respiratory burst). The results from the present study indicate that under the experimental conditions evaluated, P. incarnata treatment during gestation and lactation presented antioxidant activity in the absence of maternal reproductive toxicity.
Passiflora incarnata é comercializada em muitos países como fitoterápico. Embora a bula da maioria dos fitoterápicos recomende que eles sejam usados sob supervisão médica, estudos sobre a toxicidade reprodutiva e do desenvolvimento desses produtos são raros e não obrigatórios para fins regulatórios. Neste estudo, realizamos uma avaliação da toxicidade reprodutiva da P. incarnata, administrada a ratas Wistar (30 ou 300 mg/kg, gavagem) durante a gestação e a lactação. Além disso, considerando as propriedades antioxidantes que têm sido atribuídas aos flavonoides presentes no gênero Passiflora, também avaliou-se o equilíbrio antioxidante/pró-oxidante no plasma destas fêmeas e conduziu-se um teste in vitro para avaliar o potencial antioxidante. O tratamento com P. incarnata não influenciou o peso corporal das fêmeas, bem como indicadores de toxicidade reprodutiva (perdas pós-implantação, número de filhotes vivos e peso da ninhada) e os parâmetros de função hepática (albumina, AST, ALT, GGT). A propriedade antioxidante da P. incarnata foi evidenciada tanto in vivo (aumento do potencial antioxidante total plasmático) quanto in vitro (diminuição do burst respiratório em neutrófilos). Os resultados deste estudo indicam que, nas condições experimentais avaliadas, o tratamento com P. incarnata durante a gestação e lactação apresentou efeito antioxidante, na ausência de toxicidade reprodutiva materna.
Assuntos
Ratos , Lactação , /análise , Ratos Wistar/classificação , Gravidez , Estresse Oxidativo , Medicamento FitoterápicoRESUMO
Fluoxetine (FLX) is commonly used to treat anxiety and depressive disorders in pregnant women. Since FLX crosses the placenta and is excreted in milk, maternal treatment with this antidepressant may expose the fetus and neonate to increased levels of serotonin (5-HT). Long-term behavioral abnormalities have been reported in rodents exposed to higher levels of 5-HT during neurodevelopment. In this study we evaluated if maternal exposure to FLX during pregnancy and lactation would result in behavioral and/or stress response disruption in adolescent and adult rats. Our results indicate that exposure to FLX influenced restraint stress-induced Fos expression in the amygdala in a gender and age-specific manner. In male animals, a decreased expression was observed in the basolateral amygdala at adolescence and adulthood; whereas at adulthood, a decrease was also observed in the medial amygdala. A lack of FLX exposure effect was observed in females and also in the paraventricular nucleus of both genders. Regarding the behavioral evaluation, FLX exposure did not induce anhedonia in the sucrose preference test but decreased the latency to feed of both male and female adolescent rats evaluated in the novelty-suppressed feeding test. In conclusion, FLX exposure during pregnancy and lactation decreases acute amygdalar stress response to a psychological stressor in males (adolescents and adults) as well as influences the behavior of adolescents (males and females) in a model that evaluates anxiety and/or depressive-like behavior. Even though FLX seems to be a developmental neurotoxicant, the translation of these findings to human safe assessment remains to be determined since it is recognized that not treating a pregnant or lactating woman may also impact negatively the development of the descendants.
Assuntos
Envelhecimento , Fluoxetina/farmacologia , Lactação/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Caracteres Sexuais , Tonsila do Cerebelo/metabolismo , Animais , Feminino , Masculino , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/metabolismo , Gravidez , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Wistar , Estresse Psicológico/etiologia , Estresse Psicológico/metabolismoRESUMO
In 2009 the Brazilian Ministry of Health published a document named RENISUS that lists 71 herbs traditionally used in Brazil that could result in phytomedicines to be dispensed by the governmental health care program. This manuscript reviews female reproductive and/or developmental toxicity information of these herbs. More than half (35) of the herbs lack information regarding female reproductive and/or developmental effects. From the fourteen herbs used traditionally to disturb female reproduction, five present experimental data corroborating their actions as abortifacients (Maytenus ilicifolia, Momordica charantia, Plectranthus barbatus, Ruta graveolens) or labour facilitator (Bidens pilosa). For 23 of the herbs evaluated experimentally for any type of female reproductive endpoint, only a single study was retrieved and at least twelve of these studies were conducted with a single dose. This scenario suggests that the scientific power of the published information is very low and that a scientifically-based risk/benefit analysis about the use of these herbs during pregnancy is not possible. Considering the appeal that phytomedicines have for pregnant women, usually aware and afraid of the risks that synthetic drugs may have in their pregnancy and progeny, well designed studies evaluating reproductive and/or developmental toxicity of these herbs urge.