RESUMO
Recent years have seen an increase in the use of antidepressant drugs, especially fluoxetine (FLX), in sensitive populations, such as pregnant and lactating women. Although some evidence suggests a possible endocrine action of FLX, no specific studies have been performed to investigate this hypothesis. In the present study, we investigated the possible (anti)androgenic and (anti)estrogenic actions of FLX using Hershberger, uterotrophic (0.4, 1.7, and 17mg/kg), and reporter gene (7.6-129µM) assays. In the Hershberger assay, no differences were observed in androgen-dependent organ weights. However, the uterotrophic and gene reporter assays indicated a possible estrogenic action of FLX. Uterine weight increased in the 1.7 and 17mg/kg/day groups in the 3-day uterotrophic assay in immature rats. Additionally, noncytotoxic concentrations of FLX induced estrogenic responses and increased the estrogenic response of estradiol in MCF-7 breast cancer cells transfected with luciferase.
Assuntos
Antidepressivos de Segunda Geração/toxicidade , Estrogênios não Esteroides/toxicidade , Fluoxetina/toxicidade , Receptores de Estrogênio/metabolismo , Útero/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Feminino , Genitália Masculina/anatomia & histologia , Genitália Masculina/efeitos dos fármacos , Humanos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Útero/patologiaRESUMO
AIM OF THE STUDY: Investigate the possible effects of Tribulus terrestris (TT) on endocrine sensitive organs in intact and castrated male rats as well as in a post-menopausal rat model using ovariectomized females. MATERIALS AND METHODS: Three different dose levels of TT (11, 42 and 110 mg/kg/day) were administered to castrated males for 7 days and to intact males and castrated females for 28 days. In addition to TT treatment, all experiments also included a group of rats treated with dehydroepiandrosterone (DHEA). In experiments using castrated males and females we also used testosterone and 17 alpha-ethynylestradiol, respectively, as positive controls for androgenicity and estrogenicity. RESULTS: Neither DHEA nor TT was able to stimulate androgen sensitive tissues like the prostate and seminal vesicle in both intact and castrated male rats. In addition, administration of TT to intact male rats for 28 days did not change serum testosterone levels as well as did not produce any quantitative change in the fecal excretion of androgenic metabolites. However, a slight increase in the number of homogenization-resistant spermatids was observed in rats treated with 11 mg/kg/day of TT extract. In ovariectomized females, TT did not produce any stimulatory effects in uterine and vaginal epithelia. CONCLUSIONS: Tribulus terrestris was not able to stimulate endocrine sensitive tissues such as the prostate, seminal vesicle, uterus and vagina in Wistar rats, indicating lack of androgenic and estrogenic activity in vivo. We also showed a positive effect of TT administration on rat sperm production, associated with unchanged levels of circulating androgens.
Assuntos
Androgênios/farmacologia , Extratos Vegetais/farmacologia , Espermátides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Tribulus/química , Androgênios/administração & dosagem , Androgênios/metabolismo , Animais , Castração , Contagem de Células , Relação Dose-Resposta a Droga , Epitélio/efeitos dos fármacos , Fezes/química , Feminino , Masculino , Medicina Tradicional , Tamanho do Órgão/efeitos dos fármacos , Especificidade de Órgãos , Fitoterapia , Extratos Vegetais/administração & dosagem , Próstata/efeitos dos fármacos , Próstata/patologia , Ratos , Ratos Wistar , Glândulas Seminais/efeitos dos fármacos , Glândulas Seminais/patologia , Testículo/patologia , Testosterona/sangue , Testosterona/metabolismo , Útero/efeitos dos fármacos , Útero/patologia , Vagina/efeitos dos fármacos , Vagina/patologiaRESUMO
UNLABELLED: Different products of plant Morinda citrifolia L. (noni) have been marketed and used around the world based on properties described by Polynesian people that use them for more than 2000 years. Marketing of these products is based on their presumptive phytotherapic properties. However there is little scientific evidence about their safety, especially when used during pregnancy. AIM OF THE STUDY: Evaluate the possible developmental toxicity of the noni fruit aqueous extract and commercial product of TAHITIAN NONI juice in rats exposed during pregnancy. MATERIALS AND METHODS: Pregnant Wistar rats were exposed by gavage to 7, 30 and 300 mg/kg bw (body weight) of noni aqueous extract or to 0.4, 2 and 20 mL/kg bw (body weight) of noni juice between day 7 and day 15 of pregnancy. Caesarean sections were performed on day 20 of pregnancy and reproductive parameters were evaluated. Implantations sites and postimplantation losses were recorded. Fetuses were weighted and examined for externally visible anomalies. After, the fetuses were cleared with KOH and the bones stained with alizarin red. Skeletal alterations of the skull, vertebral column, ribs, forelimbs, hindlimbs, sternum, sings of delayed ossification and variations were examined in accordance with pre-defined criteria and identified using harmonized and internationally accepted nomenclature recommended by the International Federation of Teratology Societies. RESULTS: Exposure with extract and juice of Morinda citrifolia did not induce maternal toxicity at the tested doses, but induced delayed ossification in fetuses. CONCLUSION: The exposure of pregnant rats to aqueous extract or juice Morinda citrifolia during organogenesis period may induce adverse effects on the normal development of fetuses. These findings indicate the need for further studies with noni derivates preceding their use in pregnant women.
Assuntos
Desenvolvimento Ósseo/efeitos dos fármacos , Morinda/química , Extratos Vegetais/farmacologia , Teratogênicos/farmacologia , Animais , Relação Dose-Resposta a Droga , Feminino , Gravidez , Resultado da Gravidez , Ratos , Ratos WistarRESUMO
Phthalates are chemicals employed in several industrial products and there is a growing body of evidence demonstrating that they induce numerous adverse effects on the reproductive system. This study was carried out to assess possible alterations induced by the plasticizer di(2-ethylhexyl phthalate (DEHP) on cholesterol, testosterone, and thyroxine (total T4) levels, as well as to discuss the significance of these data in global changes observed in the reproductive tract of pubertal animals. Wistar rats aged 21 days received DEHP orally at 0, 250, 500, and 750 mg/kg/day for 30 days and were examined for different reproductive endpoints. At the end of the treatment, significant decreases in relative weight of testosterone-dependent organs, delayed preputial separation, and low serum testosterone were observed at the highest DEHP dose. The plot of the relationship between DEHP dose and serum cholesterol revealed a biphasic effect. The concentration of cholesterol in serum was significantly reduced at 250 mg/kg/day DEHP but returned to control values at 750 mg/kg/day. Cholesterol levels measured in testicular tissue increased with DEHP treatment. Serum T4 levels were not affected by DEHP at any dose, indicating the absence of a link between total thyroxin concentration and phthalate effects on cholesterol levels. Taken together these results indicate that effects observed in serum and testicular cholesterol levels may reflect distinct effects of DEHP on cholesterol synthesis and usage. These results confirm and extend previously reported findings showing that alterations in cholesterol balance may play a role in the suppression of steroidogenesis induced by DEHP in rats.