RESUMO
The objective of this work was to develop a food additive for the sex reversal of Nile tilapia (Oreochromis niloticus) based on a simple oil in water (O/W) nanoemulsion with testosterone propionate for incorporation into commercial feed. Oil screening and evaluation of the organoleptic and physicochemical characteristics were carried out to determine the best formulation. A palatability test was also performed. Sex reversal test was assayed using 5 experimental groups: negative control - macerated feed without hormone; free testosterone - macerated feed with 60 mg/kg of testosterone propionate diluted in ethanol; and macerated feed with testosterone propionate nanoemulsion at a concentration of 30, 60, and 90 mg/kg. Stable nanoemulsions (size 76-210 nm) with testosterone propionate were produced. All nanoemulsion-added feed was palatable to tilapia. We obtained sex reversal values of ≈65, 75, and 72% in the groups of 30, 60, and 90 mg/kg, respectively. We can conclude that the nanoemulsion showed promising results; it is capable of inducing sex reversal in tilapia, is suitable as a commercial product, and has the potential to promote safety for rural staff and reduce the environmental impact of hormones.
Assuntos
Ciclídeos , Propionato de Testosterona , Tilápia , Animais , Testosterona , Ração AnimalRESUMO
Early life exposure to sex hormones affects several brain areas involved in regulating locomotor and motivation behaviors. Our group has shown that neonatal exposure to testosterone propionate (TP) or estradiol valerate (EV) affected the brain dopamine (DA) system in adulthood. Here, we studied the long-lasting effects of neonatal exposure to sex hormones on behavioral and neurochemical responses to amphetamine (AMPH) and methylphenidate (MPD). Our results show that AMPH-induced locomotor activity was higher in female than male control rats. The conditioned place preference (CPP) to AMPH was only observed in EV male rats. In EV female rats, AMPH did not increase locomotor activity, but MPD-induced CPP was observed in control, EV and TP female rats. Using in vivo brain microdialysis, we observed that AMPH-induced extracellular DA levels were lower in nucleus accumbens (NAcc) of EV and TP female rats than control rats. In addition, MPD did not increase NAcc extracellular DA levels in EV rats. Using in vivo fast-scan cyclic voltammetry in striatum, MPD-induced DA reuptake was higher in EV than control rats. In summary, our results show that early life exposure to sex hormones modulates mesolimbic and nigrostriatal DA neurons producing opposite neurochemical effects induced by psychostimulant drugs in NAcc or striatum.
Assuntos
Estimulantes do Sistema Nervoso Central , Metilfenidato , Transtornos Relacionados ao Uso de Substâncias , Propionato de Testosterona , Anfetamina/farmacologia , Animais , Estimulantes do Sistema Nervoso Central/farmacologia , Dopamina/farmacologia , Estradiol/farmacologia , Feminino , Masculino , Metilfenidato/farmacologia , Atividade Motora , Núcleo Accumbens , RatosRESUMO
To investigate the effects of the previous administration of testosterone propionate (TP) on the morphology of the gastrocnemius muscle of Wistar rats submitted to ladder-based resistance training (LRT). Twenty-eight rats were divided equally into groups: initial control (CI), 4-week TP (CT4), 4-week TP + LRT (TRT), and placebo + LRT (RT). The rats from the CT4 and TRT groups were treated with TP for four weeks (10 mg/kg/week). TRT and RT trained for ten weeks. The rodents were euthanized at the end of the experiment, and gastrocnemius muscle, prostate, and left and right testicles were collected. There was no statistical difference between the RT and TRT for final volume load. The prostate mass of the TRT and RT groups was statistically heavier than the CT4 group (P < 0.01). The TRT group's prostate/body mass ratio was statistically different from the CT4 group (P < 0.05). The TRT group was shown to have larger type I, type II, and mean fCSA fibers than all other groups (P < 0.001). Regarding the nuclei/fiber ratio (N/f), the CT4, RT, and TRT groups had higher values than CI (P < 0.01). In addition, the RT group showed a higher N/f ratio than CT4 (P < 0.001) but lower than TRT (P < 0.001). In conclusion, short-term TP administration before resistance training can elicit a greater N/f ratio and size of the mean fCSA of the Gastrocnemius muscle of young adult Wistar rats than resistance training alone.
Assuntos
Treinamento Resistido , Propionato de Testosterona , Animais , Humanos , Hipertrofia , Masculino , Músculo Esquelético , Ratos , Ratos Wistar , Testosterona , Propionato de Testosterona/farmacologiaRESUMO
BACKGROUND: We aimed to evaluate the effects of different therapeutic options to prevent the evolution of vaginal stenosis after pelvic radiotherapy in women with cervical cancer. METHODS: open-label randomized clinical trial of 195 women, stage I-IIIB, aged 18-75 years, using topical estrogen (66), topical testosterone (34), water-based intimate lubricant gel (66), and vaginal dilators (29) to assess the incidence and severity of vaginal stenosis after radiotherapy at UNICAMP-Brazil, from January/2013 to May/2018. The main outcome measure was vaginal stenosis assessed using the Common Terminology Criteria for Adverse Events (CTCAE) scale and percental changes in vaginal volume. The women were evaluated at four different times: shortly after the end of radiotherapy, and four, eight, and 12 months after the beginning of the intervention. Statistical analysis was carried out using Symmetry test, Kruskal-Wallis test and multiple regression. RESULTS: the mean age of women was 46.78 (±13.01) years, 61,03% were premenopausal and 73,84% had stage IIB-IIIB tumors. The mean reduction in vaginal volume in the total group was 25.47%, with similar worsening in the four treatment groups with no statistical difference throughout the intervention period. There was worsening of vaginal stenosis evaluated by CTCAE scale after 1 year in all groups (p < 0.01), except for the users of vaginal dilator (p = 0.37). CONCLUSIONS: there was a reduction in vaginal volume in all treatment groups analyzed, with no significant difference between them. However, women who used vaginal dilators had a lower frequency and severity of vaginal stenosis assessed by the CTCAE scale after one year of treatment. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials, RBR-23w5fv . Registered 10 January 2017 - Retrospectively registered.
Assuntos
Braquiterapia/efeitos adversos , Quimiorradioterapia/efeitos adversos , Lesões por Radiação/epidemiologia , Neoplasias do Colo do Útero/radioterapia , Doenças Vaginais/epidemiologia , Administração Tópica , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Quimiorradioterapia/métodos , Constrição Patológica/diagnóstico , Constrição Patológica/epidemiologia , Constrição Patológica/etiologia , Constrição Patológica/prevenção & controle , Dilatação/instrumentação , Dilatação/métodos , Estrogênios Conjugados (USP)/administração & dosagem , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Lesões por Radiação/prevenção & controle , Índice de Gravidade de Doença , Propionato de Testosterona/administração & dosagem , Resultado do Tratamento , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Vagina/efeitos dos fármacos , Vagina/patologia , Vagina/efeitos da radiação , Doenças Vaginais/diagnóstico , Doenças Vaginais/etiologia , Doenças Vaginais/prevenção & controle , Adulto JovemRESUMO
Serum analysis has received much attention in regulatory analysis of food-producing animals, especially for anabolic steroids. The possibility of confirming the parent drugs with minimum metabolization enables the detection of intact steroid esters, whose identification represents unequivocal proof of drug administration. This work involved the development and validation of a quantitative LC-MS/MS method to determine 30 steroids and steroid esters in bovine serum. Sensitivity was improved using microwave-assisted chemical derivatization with methoxyamine hydrochloride. The validation was successfully conducted in accordance with the Decision 657/2002/EC guidelines. An in vivo experiment was performed on 12 crossbred steers in which two commercial formulations containing boldenone undecylenate and testosterone propionate were administrated via intramuscular injections. The samples were collected over a period of 120 days, in which both intact esters were identified within 11 days postadministration. 17ß-Boldenone was observed after 92 days for 2 steers and 56 days for the other animals. The applicability of a cut-off level to the ratio between 17ß-testosterone and epitestosterone was evaluated in an attempt to differentiate testosterone abuse from endogenous production. It could be observed that a calculated ratio above this level is strong evidence of drug administration, although a high false-negative rate was obtained.
Assuntos
Bovinos/sangue , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Propionato de Testosterona/sangue , Testosterona/análogos & derivados , Anabolizantes/sangue , Animais , Resíduos de Drogas/química , Masculino , Testosterona/sangueRESUMO
Background: Both supraphysiological and subphysiological testosterone levels are associated with increased cardiovascular risk. Testosterone consumption at supraphysiological doses has been linked to increased blood pressure, left ventricular hypertrophy, vascular dysfunction, and increased levels of inflammatory markers. Activation of the NLRP3 inflammasome contributes to the production of proinflammatory cytokines, leading to cardiovascular dysfunction. We hypothesized that supraphysiological levels of testosterone, via generation of mitochondrial reactive oxygen species (mROS), activates the NLRP3 inflammasome and promotes vascular dysfunction. Methods: Male, 12 week-old C57Bl/6J (WT) and NLRP3 knockout (NLRP3-/-) mice were used. Mice were treated with testosterone propionate [TP (10 mg/kg) in vivo] or vehicle for 30 days. In addition, vessels were incubated with testosterone [Testo (10-6 M, 2 h) in vitro]. Testosterone levels, blood pressure, vascular function (thoracic aortic rings), pro-caspase-1/caspase-1 and interleukin-1ß (IL-1ß) expression, and generation of reactive oxygen species were determined. Results: Testosterone increased contractile responses and reduced endothelium-dependent vasodilation, both in vivo and in vitro. These effects were not observed in arteries from NLRP3-/- mice. Aortas of TP-treated WT mice (in vivo), as well as aortas from WT mice incubated with testo (in vitro), exhibited increased mROS levels and increased caspase-1 and IL-1ß expression. These effects were not observed in arteries from NLRP3-/- mice. Flutamide [Flu, 10-5 M, androgen receptor (AR) antagonist], carbonyl cyanide m-chlorophenyl hydrazone (CCCP, 10-6 M, mitochondrial uncoupler) and MCC950 (MCC950, 10-6 M, a NLRP3 receptor inhibitor) prevented testosterone-induced mROS generation. Conclusion: Supraphysiological levels of testosterone induce vascular dysfunction via mROS generation and NLRP3 inflammasome activation. These events may contribute to increased cardiovascular risk.
Assuntos
Androgênios/toxicidade , Aorta Torácica/efeitos dos fármacos , Inflamassomos/agonistas , Mitocôndrias/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/agonistas , Espécies Reativas de Oxigênio/metabolismo , Propionato de Testosterona/toxicidade , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Animais , Aorta Torácica/metabolismo , Aorta Torácica/fisiopatologia , Caspase 1/metabolismo , Inflamassomos/genética , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/deficiência , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptores Androgênicos/efeitos dos fármacos , Receptores Androgênicos/metabolismo , Técnicas de Cultura de TecidosRESUMO
Hair analysis has attracted great attention in the regulatory analysis of food-producing animals, particularly due to the wider detection window of veterinary drugs in this matrix and also the possibility of confirming parent drugs with minimum metabolization. This work involved the development and validation of a quantitative liquid chromatography-tandem mass spectrometry method to determine 25 steroids and steroid esters in bovine hair. Sensitivity was improved using a fast and effective microwave-assisted chemical derivatization with methoxyamine hydrochloride. The validation was conducted in accordance with the Decision 657/2002/EC guidelines. An animal experimentation procedure was performed on 12 bovine animals in which two commercial formulations containing boldenone undecylenate and testosterone propionate were administrated via intramuscular injections on the neck. The samples were collected for 78 days in which the detection of the administrated analytes was only observed near the application sites. For some of the monitored days, no analyte was detected on the neck area. Since the migration of the analytes was not observed in areas other than the application site, false-negative results should be carefully considered when monitoring animal hair samples.
Assuntos
Cromatografia Líquida/métodos , Cabelo/química , Esteroides/análise , Espectrometria de Massas em Tandem/métodos , Animais , Bovinos , Cromatografia Líquida/veterinária , Ésteres/análise , Ésteres/química , Masculino , Micro-Ondas , Esteroides/química , Espectrometria de Massas em Tandem/veterinária , Testosterona/análogos & derivados , Testosterona/análise , Propionato de Testosterona/análise , Drogas Veterinárias/análiseRESUMO
Telocytes are CD34-positive cells with a fusiform cell body and long, thin cytoplasmic projections called telopodes. These cells were detected in the stroma of various organs, including the prostate. The prostate is a complex gland capable of undergoing involution due to low testosterone levels; and this condition can be reversed with testosterone replacement. Telocyte function in the mature prostate remains to be dermined, and it is not known whether telocytes can take place in tissue remodeling during prostate involution and regrowth. The present study employed structural, ultrastructural and immunohistochemical methods to investigate the telocyte's phenotypes in the ventral prostate (VP) from control (CT), castrated (CS) and testosterone replacement (TR) groups of adult male Wistar rats. Telocytes were found in the subepithelial, perimuscular and interstitical regions around glandular acini. Telocytes from CT animals have condensed chromatin and long and thin telopodes. In CS group, telocytes appeared quiescent and exhibited layers of folded up telopodes. After TR, telocytes presented loose chromatin, abundant rough endoplasmic reticulum and enlarged telopodes, closely associated with bundles of collagen fibrils. We called these cells "telocytes with a synthetic phenotype". As testosterone levels and glandular morphology returned toward to the CT group parameters, after 10 days of TR, these telocytes progressively switched to the normal phenotype. Our results demonstrate that telocytes exhibit phenotypic plasticity upon androgen manipulation and interact with fibroblast and smooth muscle cells to maintain glandular architecture in control animals and during tissue remodeling after hormonal manipulation.
Assuntos
Próstata/citologia , Telócitos/citologia , Propionato de Testosterona/administração & dosagem , Animais , Antígenos CD34/metabolismo , Masculino , Orquiectomia , Próstata/efeitos dos fármacos , Próstata/crescimento & desenvolvimento , Próstata/metabolismo , Ratos , Ratos Wistar , Telócitos/efeitos dos fármacos , Telócitos/metabolismo , Testosterona/sangue , Propionato de Testosterona/farmacologiaRESUMO
The main clinical feature associated with hyperandrogenism in polycystic ovary syndrome (PCOS) in humans is hirsutism, where hair increases its length, pigmentation, and particularly its diameter. Currently, it is not known whether PCOS animal models also exhibit changes in the hair. Therefore, the aim of this study was to explore the wool characteristics in sheep prenatally androgenized (PA) with testosterone propionate. After 4 and 13 months of life, wool was collected from the top of the shoulder of both females and males (both androgenized and controls). The offspring sheep were followed for up to 19 months of life to evaluate testosterone and androstenedione serum levels by ultra-high-performance liquid chromatography-tandem mass spectrometry, determine insulin and glucose response to intravenous glucose tolerance test, and address estrus cyclicity during the second breeding season. PA male animals showed a reduction in wool fiber diameter at 4 months of age compared with controls (P = 0.02) but not at 13 months, whereas PA females showed increased hair diameter at 13 months (P = 0.002), with no difference at 4 months. No substantial changes in other hair parameters (length, color, and medullation) were identified. In addition, increased levels of serum testosterone were observed in PA female sheep compared with controls at 12 months (P = 0.03). Our results indicate for the first time, to our knowledge, that changes in wool fiber diameter observed in PA ewes replicate, at the translational level, the increase in hair diameter in hirsute women with PCOS.
Assuntos
Androgênios , Modelos Animais de Doenças , Hirsutismo , Síndrome do Ovário Policístico , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ovinos , Virilismo/induzido quimicamente , Animais , Feminino , Teste de Tolerância a Glucose , Hirsutismo/sangue , Hirsutismo/induzido quimicamente , Hirsutismo/complicações , Hirsutismo/patologia , Hiperandrogenismo/sangue , Hiperandrogenismo/induzido quimicamente , Hiperandrogenismo/patologia , Masculino , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/patologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/patologia , Propionato de Testosterona , Virilismo/sangue , Virilismo/patologiaRESUMO
Research in programming is focused on the study of stimuli that alters sensitive periods in development, such as prenatal and neonatal stages, that can produce long-term deleterious effects. These effects can occur in various organs or tissues such as the brain, affecting brain circuits and related behaviors. Our laboratory has demonstrated that neonatal programming with sex hormones affects the mesocorticolimbic circuitry, increasing the synthesis and release of dopamine (DA) in striatum and nucleus accumbens (NAcc). However, the behavioral response to psychostimulant drugs such as methylphenidate and the possible mechanism(s) involved have not been studied in adult rats exposed to sex hormones during the first hours of life. Thus, the aim of this study was to examine the locomotor activity induced by methylphenidate (5mg/kg i.p.) and the expression of the DA transporter (DAT) in NAcc of adult rats exposed to a single dose of testosterone propionate (TP: 1mg/50µLs.c.) or estradiol valerate (EV: 0.1mg/50µLs.c.) at postnatal day 1. Our results demonstrated that adult female rats treated with TP have a lower methylphenidate-induced locomotor activity compared to control and EV-treated adult female rats. This reduction in locomotor activity is related with a lower NAcc DAT expression. However, neither methylphenidate-induced locomotor activity nor NAcc DAT expression was affected in EV or TP-treated adult male rats. Our results suggest that early exposure to sex hormones affects long-term dopaminergic brain areas involved in the response to psychostimulants, which could be a vulnerability factor to favor the escalating doses of drugs of abuse.