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1.
Life Sci ; 242: 117227, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31881226

RESUMO

INTRODUCTION: Misuse of AAS is emergent among both genders, however, few studies were performed evaluating AAS effects on female body and none evaluate the impact of nandrolone decanoate (ND) in renal function. AIM: Determine the effects of chronic treatment with ND on kidney function of female rats and evaluate the influence of oxidative stress on it. MATERIAL AND METHODS: Female rats were separated into two groups (n = 8 each), the treated group (DECA), which received ND at a dose of 20 mg/kg/week (i.m), and the control group (C), which was treated with the vehicle (peanut oil, i.m.). All treatments were performed during eight weeks. After this period, 24 h urine, blood and organs (heart, gastrocnemius muscle, liver and kidney) were collected. Organ hypertrophy was calculated, and kidney collagen content was evaluated. AOPP, TBARS, SOD and catalase activity were determined in the kidney. Moreover, proteinuria and creatinine clearance were also investigated. KEY-FINDINGS: Hypertrophy was observed in the liver, gastrocnemius muscle, heart and kidney. Kidney hypertrophy was followed by a reduced organ function and an increase in collagen deposition. Oxidative stress upsurge occurred in both proteins and lipids, followed by a reduction in SOD activity. SIGNIFICANCE: Administration of DN in rats was followed by renal damage and kidney fibrosis due to increased oxidative stress on that organ.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Anabolizantes/efeitos adversos , Homeostase/efeitos dos fármacos , Decanoato de Nandrolona/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/fisiopatologia , Anabolizantes/farmacologia , Animais , Western Blotting , Catalase/metabolismo , Feminino , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Rim/fisiologia , Decanoato de Nandrolona/farmacologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
2.
Braz. J. Pharm. Sci. (Online) ; 56: e18289, 2020. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1089218

RESUMO

Metabolism of anabolic androgenic steroids is important for its physiological effects. The aim was to investigate the effects of finasteride (a 5α-reductase inhibitor - 5αR) on cardiac and mutagenic effects promoted by ND. Male Wistar rats were separated into three groups: CONT, received the vehicles of ND and finasteride (Peanut oil+Saline); DECA group, received ND (20 mg.kg.week-1, i.m.), and DECAF received ND and finasteride (100 µg.kg-1, i.p.), for four weeks. After, hypertrophy, cytokines and Angiotensin Converting Enzyme (ACE) activity was determined in heart. Bone marrow was used for micronucleus evaluation. Treatment with ND promotes increase in cardiac hypertrophy, ACE activity and disbalance among pro- and anti-inflammatory cytokines, and combination with finasteride worsened those effects. Association with finasteride ameliorates the toxic effects of ND on bone marrow cells, as was observed by a normalization of the number of micronucleate polychromatic erythrocytes and the mitotic index. Our data demonstrates that deleterious effects promoted by ND are depend, at least in part, of its metabolization. Also, inhibition of 5αR by finasteride present variated effects dependent on organ studied. It can promote increase on cardiac damage and a reduction on mutagenic effects of ND, which demonstrated that dehydronandrolone has diverse role on ND effects..

3.
Toxicol Appl Pharmacol ; 301: 22-30, 2016 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-27074353

RESUMO

UNLABELLED: Anabolic-androgenic steroids are misused, including by women, but little is known about the cardiovascular effects of these drugs on women. AIM: To evaluated the effects of nandrolone decanoate (ND) and resistive physical exercise on cardiac contractility in young female rats. MAIN METHODS: Female Wistar rats were separated into 4 groups: C (untrained animals); E (animals were submitted to resistance exercise by jumping in water 5 times per week); ND (animals were treated with ND, 20mg/kg/week for 4weeks); and NDE (trained and treated). The haemodynamic parameters (+dP/dtmax, -dP/dtmin and Tau) were assessed in the left ventricle. The heart was collected for histological analyses and collagen deposition. The gastrocnemius muscle was weighed, and hypertrophy was assessed by the ratio of their weights to gastrocnemius/tibia length. The expression of calcium handling proteins was measured by western blot analysis. RESULTS: ND treatment and physical exercise increased cardiac contractility and relaxation. In addition, ND promoted increases in phospholamban phosphorylated (p-PLB) and isoforms of sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2a) expression, while resistance exercise increased the phosphorylation of PLB and expression of Na(+)/Ca(2+) exchangers (NCX). Cardiac hypertrophy and collagen deposition were observed after ND treatment. CONCLUSION: Regulatory components of cytosolic calcium, such as SERCA2a and p-PLB, play important roles in modulating the contractility and relaxation effects of ND in females.


Assuntos
Anabolizantes/farmacologia , Nandrolona/análogos & derivados , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Trocador de Sódio e Cálcio/metabolismo , Função Ventricular Esquerda/fisiologia , Remodelação Ventricular/fisiologia , Animais , Pressão Arterial/efeitos dos fármacos , Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Cardiomegalia/induzido quimicamente , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Colágeno/metabolismo , Feminino , Frequência Cardíaca/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Nandrolona/farmacologia , Decanoato de Nandrolona , Ratos Wistar
4.
Life Sci ; 137: 65-73, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26165753

RESUMO

UNLABELLED: Anabolic-androgenic steroids are misused, including women, but little is known about the cardiovascular effects of these drugs on females. AIM: Evaluated the effects of nandrolone decanoate (ND), physical exercise and estrogen deficiency on female rats. MAIN METHODS: Female Wistar rats were divided into 8 groups: S and OVX: (SHAM: sham surgery; OVX: ovariectomy, vehicle), SE and OVXE (resistance exercise 5 times a week, vehicle), SD and OVXD (treated with ND, 20 mg/kg/week for 4 weeks); SDE and OVXDE. Treatments were initiated 21 days after surgery. The Bezold­Jarisch reflex was assessed by Phenylbiguanide administration. The right atrium, kidney, and serum were collected for molecular analyses by RT-PCR of atrial natriuretic peptide (ANP), A-type natriuretic peptide receptor (NPR-A) and NPR-C. ELISA assay to estradiol and testosterone concentrations. The gastrocnemius muscle, heart and kidney weights/tibia length were measured.Morphometric analysis of heart was made (H/E) and collagen content of heart and kidney were evaluated using Pirossirius Red. KEY FINDINGS: ND treatment increased ANP expression on atrium and decreased NPR-A expression in kidney. Physical exercise and ovariectomy did not alter this parameter. NPR-C level was reduced in the SDE and OVXDE. Renal and cardiac hypertrophy was observed after ND treatment, with collagen deposition. Plasma estrogen concentrations were reduced and serum testosterone concentrations were increased after ND treatment. SIGNIFICANCE: ANP has an important role in modulating the cardiovascular effects of ND in females. Thismodulating may have occurred by the increasing ANP expression, reducing NPR-A and NPR-C expression levels, and changing sex hormone levels.


Assuntos
Pressão Arterial/efeitos dos fármacos , Fator Natriurético Atrial/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Nandrolona/análogos & derivados , Anabolizantes/farmacologia , Animais , Pressão Arterial/fisiologia , Barorreflexo/efeitos dos fármacos , Biguanidas/farmacologia , Colágeno/metabolismo , Estradiol/sangue , Estrogênios/deficiência , Feminino , Expressão Gênica/efeitos dos fármacos , Coração/anatomia & histologia , Átrios do Coração/efeitos dos fármacos , Átrios do Coração/metabolismo , Frequência Cardíaca/fisiologia , Hipertrofia , Rim/anatomia & histologia , Rim/metabolismo , Músculo Esquelético/anatomia & histologia , Miocárdio/metabolismo , Nandrolona/farmacologia , Decanoato de Nandrolona , Peptídeo Natriurético Tipo C/biossíntese , Tamanho do Órgão/efeitos dos fármacos , Ovariectomia , Condicionamento Físico Animal , Ratos , Receptores do Fator Natriurético Atrial/biossíntese , Testosterona/sangue , Tíbia/anatomia & histologia
5.
Braz. j. pharm. sci ; 50(2): 309-320, Apr-Jun/2014. tab, graf
Artigo em Inglês | LILACS | ID: lil-722192

RESUMO

The aims of this study were to evaluate the chemical profile, vascular reactivity, and acute hypotensive effect (AHE) of the ethanolic extract of leaves of Alpinia purpurata (Vieill) K. Schum (EEAP). Its chemical profile was evaluated using HPLC-UV, ICP-OES, and colorimetric quantification of total flavonoids and polyphenols. The vascular reactivity of the extract was determined using the mesenteric bed isolated from WKY. AHE dose-response curves were obtained for both EEAP and inorganic material isolated from AP (IAP) in WKY and SHR animals. Cytotoxic and mutagenic safety levels were determined by the micronucleus test. Rutin-like flavonoids were quantified in the EEAP (1.8 ± 0.03%), and the total flavonoid and polyphenol ratios were 4.1 ± 1.8% and 5.1 ± 0.3%, respectively. We observed that the vasodilation action of EEAP was partially mediated by nitric oxide (·NO). The IAP showed the presence of calcium (137.76 ± 4.08 μg mg-1). The EEAP and IAP showed an AHE in WKY and SHR animals. EEAP did not have cytotoxic effects or cause chromosomic alterations. The AHE shown by EEAP could result from its endothelium-dependent vascular action. Rutin-like flavonoids, among other polyphenols, could contribute to these biological activities, and the calcium present in EEAP could act in a synergistic way.


Os objetivos deste estudo foram avaliar o perfil químico de folhas de Alpinia purpurata K. Schum (AP), assim como a reatividade vascular e o efeito hipotensor agudo (EHA) do extrato etanólico de folhas de AP (EEAP). Avliou-se o perfil químico utilizando-se HPLC-UV, ICP-OES e quantificação colorimétrica de flavonoides e polifenóis totais. A reatividade vascular foi determinada utilizando leito mesentérico isolado de ratos WKY. Curvas dose-resposta do EEAP e do material inorgânico da AP (IAP) foram realizadas em animais SHR e WKY. Determinaram-se a segurança citotóxica e mutagênica pelo teste de micronúcleos. Flavonoides tipo rutina foram quantificados no EEAP (1,8±0,03%) e flavonoide total e polifenóis foram de 4,1±1,8% e 5,1±0,3%, respectivamente. Observou-se ação vasodilatadora do EEAP, mediada parcialmente pelo óxido nítrico (·NO). O IAP revelou a presença de cálcio (137,76±4.08 μg.mg-1 de Ca). O EEAP e IAP apresentaram EHA em animais WKY e SHR. Não se observaram efeitos citotóxicos e alterações cromossômicas provocadas pelo EEAP. O EEAP mostrou um EHA que poderia resultar de ação vascular dependente do endotélio. Rutina, entre outros polifenóis e flavonoides, poderia estar contribuindo para essas atividades biológicas e o cálcio presente no EEAP, poderia agir de maneira sinérgica.


Assuntos
Ratos , Zingiberaceae/classificação , Endotélio , Hipotensão/prevenção & controle , Cromatografia Líquida de Alta Pressão/classificação , Reatividade-Estabilidade , Polifenóis/análise , Classificação Internacional de Atenção Primária
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