Aquatic Plyometric Training Associated with Androgenic Anabolic Steroids do not Increase Muscle Mass in Rats

To improve athletic performance or for aesthetic reasons, athletes and no athletes may use androgenic anabolic steroids (AAS). Numerous studies have reported that aquatic plyometric training (APT) can improve muscular strength and vertical jump; however the effect of these training protocols on muscular mass are poorly investigated. The aim of this study was to investigate the effects of APT associated with AAS in the soleus, gastrocnemius (Gastro), extensor digitorium longus (EDL) and tibialis anterior (TA) skeletal muscles in rats. Animals were grouped into: sedentary (S); S with AAS (AAS); trained (T); and T with AAS (AAST). Exercised groups performed jumps in water: 4 series of 10 jumps each and 30-second rest interval between series, for 7 weeks with a progressive overload of 50 to 80% of body weight and were killed after the last exercise session. Nandrolone decanoate (5 mg/kg – supraphysiological dose) was injected subcutaneously twice a week. One way analyses of variance was performed and there was no statistically significant difference between groups in EDL (p=0.169), TA (p=0.739), Gastro (p=0.722) and Soleus (p=1.000) muscles. AAS, training or their association induced no alterations in the weight of the studied muscles. In conclusion, the APT did not increase the muscle weight as well as the association with AAS treatment

Strength training and nandrolone decanoate decreased myostatin expression

Nandrolone decanoate is a androgenic anabolic steroid (AAS) which targets the satellite cells in skeletal muscles. These cells are considered the stem cells of skeletal muscle, and they are essential for muscle growth and repair. Myostatin is a negative regulator of muscle mass that inhibits myoblast proliferation and differentiation. Recognizing the mechanisms related to AAS action in skeletal muscle is critical for a better understand of muscular physiology under AAS use. The aim of this study was to investigate the effects of aquatic plyometric training (APT) with overload associated with AAS on the gastrocnemius muscle of rats. Animals were grouped into: sedentary (S); S with AAS (AAS); trained (T); and T with AAS (AAST). Exercised groups performed jumps in water: 4 sets of 10 jumps each and 30-second rest interval between series, for 7 weeks with a progressive overload of 50 to 80% of body weight and were killed after the last exercise session. AAS (5 mg/kg – supraphysiological dose) was injected subcutaneously. One-way Anova and Turkey post hoc tests were used. Myostatin mRNA expression was determined by real-time RT-PCR. p\u3c0.05 was considered statistically significant. APT did not change myostatin expression (p=0.873). However, the interaction with AAS downregulated myostatin (p=0.039). EAA and EAAT groups expressed less myostatin than the group T (p=0.013 and p=0.009, respectively). These results should be taken with care, since other variables related to muscle remodeling should be evaluated

Nandrolone Decanoate associated with exercise training inhibit vascular endothelial growth factor (VEGF) mRNA expression in rat soleus muscle

Androgenic-anabolic steroids (AAS) have been used for both performance improvement and aesthetic reasons. It is well know that high doses of AAS induce serious adverse effects such as skeletal muscle injuries, including increase in the rate of muscle strains/ruptures. Vascular endothelial growth factor (VEGF) is a key factor in angiogenesis induction on both physiological and pathological conditions The aim of this study was to investigate VEGF mRNA expression in rat soleus muscle after jumping training associated with AAS administration. Wistar rats were grouped into: sedentary (S); trained without AAS (T); sedentary nandrolone decanoate (ND)-treated (AAS); and trained with AAS (AAST). The trained groups carried out jumps in water at 32°C.: 4 series of 10 jumps each, with a 30-second interval among series, for 7 weeks, with 50-80% overload of the animal corporal mass. The AAS (Decadurabolin® - 5mg/kg) was injected subcutaneously in the animal’s back twice a week. Real-time PCR analyses showed that training significantly increased VEGF mRNA expression in comparison with the S and AAS groups. When exercise training was associated with nandrolone decanoate, the VEGF mRNA expression was inhibited compared with T group. The inhibition of VEGF expression by AAS administration can decrease angiogenesis in skeletal muscle. These results suggest that the AAS may be strongly prejudicial to muscle remodeling and performance

Inhibition of αvβ3 integrin induces loss of cell directionality of oral squamous carcinoma cells (OSCC)

The connective tissue formed by extracellular matrix (ECM) rich in fibronectin and collagen consists a barrier that cancer cells have to overpass to reach blood vessels and then a metastatic site. Cell adhesion to fibronectin is mediated by αvβ3 and α5β1 integrins through an RGD motif present in this ECM protein, thus making these receptors key targets for cell migration studies. Here we investigated the effect of an RGD disintegrin, DisBa-01, on the migration of human fibroblasts (BJ) and oral squamous cancer cells (OSCC, SCC25) on a fibronectin-rich environment. Time-lapse images were acquired on fibronectin-coated glassbottomed dishes. Migration speed and directionality analysis indicated that OSCC cells, but not fibroblasts, showed significant decrease in both parameters in the presence of DisBa-01 (1μM and 2μM). Integrin expression levels of the α5, αv and β3 subunits were similar in both cell lines, while β1 subunit is present in lower levels on the cancer cells. Next, we examined whether the effects of DisBa-01 were related to changes in adhesion properties by using paxillin immunostaining and total internal reflection fluorescence TIRF microscopy. OSCCs in the presence of DisBa-01 showed increased adhesion sizes and number of maturing adhesion. The same parameters were analyzed usingβ3-GFP overexpressing cells and showed that β3 overexpression restored cell migration velocity and the number of maturing adhesion that were altered by DisBa-01. Surface plasmon resonance analysis showed that DisBa-01 has 100x higher affinity for αvβ3 integrin than forα5β1 integrin. In conclusion, our results suggest that the αvβ3 integrin is the main receptor involved in cell directionality and its blockage may be an interesting alternative against metastasis

La nandrolona aumenta la actividad de la enzima de conversión angiotensina en tendones de ratones

Introdução: O sistema renina-angiotensina (SRA) tem sido associado a importantes processos biológicos do corpo humano, regulando, entre outros processos, a pressão arterial e balanço hidroeletrolítico. Além disso, o SRA também regula o crescimento do tecido conjuntivo. Recentemente, foi demonstrado que a utilização de nandrolona modifica a atividade da enzima conversora de angiotensina (ECA) e aumenta a deposição de colágeno no coração. Objetivo: O objetivo do estudo foi avaliar a atividade de ECA no tendão flexor superficial (TFS) e no soro após exercício de força com administração de esteroides anabólicos androgênicos (EAA) durante sete semanas e após seis semanas de destreinamento. Métodos: Quarenta e oito ratos da linhagem Wistar foram divididos em dois grupos (G1 e G2) e subdivididos em quatro subgrupos: Sedentários (S); treinados (T); sedentários com EAA (EAAS) (Deca-Durabolin - 5mg/kg, duas vezes por semana) e treinados com administração de EAA (EAAT). Os grupos treinados realizaram saltos na água: quatro séries de 10 saltos cada, com intervalo de 30 seg entre as séries. Resultados: O treinamento aumentou a atividade de ECA no TFS em comparação ao controle (p<0,05). Os grupos tratados com EAA apresentaram maiores níveis de ECA (p<0,05). O grupo EAA-T mostrou atividade de ECA mais elevada quando comparada ao grupo T. Além disso, o grupo EAA-T apresentou maiores níveis de ECA no soro. No grupo G2, todos os subgrupos diminuíram a atividade de ECA tanto no soro quanto no tendão. Conclusão: Este estudo indica que a administração de EAA e sua combinação com o exercício aumenta a atividade de ECA nos tendões. O uso abusivo de EAA pode comprometer a adaptação tendínea no qual pode provocar remodelamento mal adaptativas.Introduction: The renin-angiotensin system (RAS) has been associated with several biological processes of the human body, regulating, among others blood pressure and water and electrolytes balance. Moreover, RAS also regulates connective tissue growth. Recently, studies have shown that the use of nandrolone modifies the angiotensin-I converting enzyme (ACE) activity and increases collagen deposition in the heart. Objective: The aim of study was to evaluate the Angiotensin-I converting enzyme (ACE) activity in the superficial flexor tendon (SFT) and in serum after load exercise in combination with anabolic androgenic steroid (AAS) administration after training session and six weeks of detraining. Methods: Forty-eight Wistar rats were used into two groups (G1 and G2) subdivided into four subgroups: Sedentary (S); trained (T); AAS-treated (Deca-Durabolin, 5mg/kg, twice a week) sedentary rats (AAS) and AAS-treated and trained animals (AAST). Trained groups performed jumps in water: four series of 10 jumps each, followed by a 30 sec interval between the series, for seven weeks. Results: Training increased ACE activity in the SFT compared to the control group (p <0.05). Both AAS and AAST groups presented higher ACE activity levels (p < 0.05). The AAST increased the ACE activity only compared to the trained animals. Only the AAST group presented significant higher levels of ACE in the serum. In the G2 group, all experimental groups presented decreased ACE activity in the serum and in the tendon, as compared to the control group. Conclusion: This study indicates that AAS administration and its combination with exercise increased ACE activity of tendons. AAS abuse could compromise tendon adaptation causing maladaptive remodeling.Introducción: El sistema renina-angiotensina (RAS) ha sido asociado con varios procesos biológicos del cuerpo humano, entre ellos, regular la presión arterial y el contenido de electrolitos. Además, el RAS también regula el tejido conectivo. Recientemente, estudios han demostrado que el uso de nandrolona modifica la actividad de ACE e incrementa la deposición de colágeno en el corazón. Objetivo: En este modo, el objetivo del estudio fue evaluar la actividad de la enzima de conversión angiotensina (ACE) en el tendón flexor superficial (TFS) y en el suero después del ejercicio de resistencia en combinación con la administración de esteroides anabólico-androgénicos (AAS) después de la sesión de entrenamiento, y seis semanas de desentrenamiento. Métodos: Cuarenta y ocho ratones Wistar fueron divididos en dos grupos (G1 y G2) y subdivididos en cuatro grupos: sedentarios (S); entrenados (T); ratas sedentarias tretratadas con AAS (Deca-Durabolin - 5 mg / kg dos veces a la semana) (AAS) y animales entrenados y tratados con AAS (AAST). Los grupos entrenados realizaron saltos en el agua: cuatro series de 10 saltos cada uno, con 30 segundos de intervalo entre las series, durante siete semanas. Resultados: El entrenamiento aumentó la actividad de ECA en TFS en comparación con el control (p <0,05). Los grupos AAS y AAST mostraron mayores niveles de ACE (p <0,05). El grupo AAST mostró alta actividad de ECA en comparación con el grupo T. Además, el AAST mostró niveles más altos de ACE en el suero. En G2, todos los grupos disminuyeron la la actividad ACE tanto en el suero como en el tendón si comparados con el grupo control. Conclusión: Este estudio indica que la administración de AAS y su combinación con el ejercicio aumenta la actividad de ECA en los tendones. El uso abusivo de AAS puede comprometer la adaptación del tendón, lo que puede causar remodelaciones mal adaptativas

Resistance training modulates the matrix mtalloproteinase-2 activity in different trabecular bones in aged rats

Background: Aging decreases osteogenic ability, inducing harmful effects on the bone extracellular matrix (ECM), while exercise training has been indicated as a tool to counteract bone disorders related to advancing age. The modulation of bone ECM is regulated by several types of matrix metalloproteinase (MMP); however, MMP-2 activity in different trabecular bones in response to resistance training (RT) has been neglected. Remodeling differs in different bones under the application of the same mechanical loading. Thus, we investigated the effects of 12 weeks of RT on MMP-2 activity in the lumbar vertebra (L6), tibia, and femur of young (3 months) and older rats (21 months). Methods: Twenty Wistar rats were divided into four groups (five animals per group): young sedentary or trained and older sedentary or trained. The 12-week RT consisted of climbing a 1.1-m vertical ladder three times per week with progressive weights secured to the animals’ tails. The animals were killed 48 h after the end of the experimental period. The MMP-2 activity was assessed by the zymography method. Results: The aging process induced lower MMP-2 activity in the lumbar vertebrae and tibia (p=0.01). RT upregulated pro, intermediate, and active MMP-2 activity in the tibia of young rats (p=0.001). RT also upregulated pro and active MMP-2 activity in the lumbar vertebrae and tibia with advancing age (p=0.01). There was no significant difference (p> 0.05) between groups for MMP-2 of the femur, regardless of age and RT. Conclusion: The aging process impairs MMP-2 activity, but RT is a potential therapeutic approach to minimize the deleterious effects of ECM degeneration in different aged bones. Distinct MMP-2 responses to exercise training may result in specific remodeling processes

Influência de diferentes protocolos de exercício e da dieta hiperlipídica sobre o sistema endocanabinóide de ratos

The objective of the study was to investigate the effects of the hyperlipid diet and the training of swimming and force on the adipose tissue, lipid profi le and endocannabinoid system of exogenous obese rats. For this, we used sixty adult male rats divided into six groups: Sedentary Standard (SP); Sedentary Hyperlipid (SH); Standard Swimming (NP); Hyperlipid Swimming (NH); Standard Force (FP); Hyperlipid Force (FH). After three weeks receiving standard or hyperlipidic diet, the animals started the exercise protocols. The NP and NH groups swam 60 minutes/day, 5 days/week with 5% body weight binding to the body, in 50x30 cm tanks, for 8 weeks. The FP and FH groups performed ladder climbing exercises with weights tied to their tails, once every three days, for 8 weeks. Animals from the SP and SH groups remained sedentary and fed their respective diets. The hyperlipid diet increased body weight gain, relative weight of adipose (epididimal, retroperitoneal, visceral and subcutaneous) and adipocyte (epididimal, retroperitoneal and visceral) areas. It also increased the fat percentage of all adipose tissues and liver, in addition to increasing the gene expression of the CB1 receptor. The trained groups had lower values of adipocyte area, improvement of lipid profi le, lower values in fat percentage of adipose tissues and liver, lower gains of body mass, and lower gene expression of CB1 receptor. Thus our results indicate the potential benefi  ts of strength and swimming training as non-pharma-cological alternatives to control the deleterious effects of the hyperlipidic diet on adipose tissue, lipid profi le, lipid content and control of the imbalance of the endocannabinoid system caused by the hyperlipidic diet.O objetivo do estudo foi investigar os efeitos da dieta hiperlipídica e do treinamento de natação e força sobre o tecido adiposo, perfil lipídico e sistema endocanabinóide de ratos obesos exógenos. Para isso, utilizamos sessenta ratos adultos machos divididos em seis grupos: Sedentário Padrão (SP); Sedentário Hiperlipídico (SH); Natação Padrão (NP); Natação Hiperlipídica (NH); Força Padrão (FP); Força Hiperlipídica (FH). Após três semanas recebendo dieta padrão ou hiperlipídica, os animais iniciaram os protocolos de exercício. Os grupos NP e NH nadaram 60 minutos/dia, 5 dias/semana com carga de 5% do peso corporal atada ao corpo, em tanques de 50x30 cm, durante 8 semanas. Os grupos FP e FH realizaram exercício de subida em escada com pesos atados às suas caudas, uma vez a cada três dias, durante 8 semanas. Os animais dos grupos SP e SH continuaram sedentários e alimentados com suas respectivas dietas. A dieta hiperlipídica aumentou o ganho de massa corporal, peso relativo dos tecidos adiposos (epididimal, retroperitoneal, visceral e subcutâneo) e área de adipócitos (epididimal, retroperitoneal e visceral). Também aumentou o percentual de gordura de todos os tecidos adiposos e fígado, além de aumentar a expressão gênica do receptor CB1. Os grupos treinados apresentaram menores valores de área de adipócitos, melhora do perfil lipídico, menores valores no percentual de gordura dos tecidos adiposos e fígado, menores ganhos de massa corporal, além de menores expressão gênica do receptor CB1. Assim nossos resultados indicam os potenciais benefícios do treinamento força e natação, como alternativas não farmacológicas para controlar os efeitos deletérios da dieta hiperlipídica sobre o tecido adiposo, perfil lipídico, conteúdo lipídico e controle do desequilíbrio do sistema endocanabinóide provocado pela dieta hiperlipídica

Palladium(II) complexes with thiosemicarbazones: syntheses, characterization and cytotoxicity against breast cancer cells and Anti-Mycobacterium tuberculosis activity

Três complexos de PdII com tiossemicarbazonas N(4)-substituídas foram preparados: [Pd(aptsc)(PPh3)](NO3) H2O, 1, [Pd(apmtsc)(PPh3)](NO3), 2, e [Pd(apptsc)(PPh3)](NO3) H2O, 3, sendo PPh3 = trifenilfosfina; Haptsc = 2-acetilpyridina-tiossemicarbazona; Hapmtsc = 2-acetilpiridina-N(4)-metil-tiossemicarbazona e Happtsc = 2-acetilpiridina-N(4)-fenil-tiossemicarbazona. Os complexos foram caracterizados por análise elementar, IR, UV-Vis, ¹H e 31P{¹H} NMR e tiveram suas estruturas cristalinas determinadas por difratometria de raios X em monocristal. Os ligantes tiossemicarbazonatos monoaniônicos atuam de modo tridentado, ligando-se ao metal pelos átomos de nitrogênio piridínico, nitrogênio azometínico e enxofre. A atividade citotóxica frente à linhagem de células tumorais MDA-MB231 (tumor de mama) e a atividade anti-Mycobacterium tuberculosis H37Rv ATCC 27294 dos compostos foram investigadas. Os complexos de PdII mostraram-se altamente ativos contra as células tumorais, com valores de IC50 em torno de 5 µmol L-1, enquanto o agente antitumoral em uso clínico cisplatina mostrou-se inativo. Os compostos apresentaram atividade anti-M. tuberculosis significante, com valores de CIM comparáveis ou melhores que aqueles referentes a alguns fármacos usados clinicamente contra tuberculose.Three PdII complexes were prepared from N(4)-substituted thiosemicarbazones: [Pd(aptsc)(PPh3)](NO3) H2O, 1, [Pd(apmtsc)(PPh3)](NO3), 2, and [Pd(apptsc)(PPh3)](NO3) H2O, 3, where PPh3 = triphenylphosphine; Haptsc = 2-acetylpyridine-thiosemicarbazone; Hapmtsc = 2-acetylpyridine-N(4)-methyl-thiosemicarbazone and Happtsc = 2-acetylpyridine-N(4)-phenyl-thiosemicarbazone. All complexes were characterized by elemental analysis, IR, UV-Vis, ¹H and 31P{¹H} NMR spectroscopies, and had their crystalline structures determined by X-ray diffractometry from single crystals. The monoanionic thiosemicarbazonate ligands act in a tridentate mode, binding to the metal through the pyridine nitrogen, the azomethine nitrogen and the sulfur atoms. The cytotoxic activity against the breast cancer cell line MDA-MB231 and the anti-Mycobacterium tuberculosis H37Rv ATCC 27294 activity were evaluated for the compounds. All PdII complexes were highly active against the studied cell line, presenting similar values of IC50, around 5 µmol L-1, while the clinically applied antitumor agent cisplatin was inactive. The compounds show remarkable anti-M. tuberculosis activities, presenting MIC values comparable or better than some commercial anti-M tuberculosis drugs

Palladium(II) complexes with thiosemicarbazones: syntheses, characterization and cytotoxicity against breast cancer cells and anti-mycobacterium tuberculosis activity

Three PdII complexes were prepared from N(4)-substituted thiosemicarbazones: [Pd(aptsc)(PPh3)](NO3)•H2O, 1, [Pd(apmtsc)(PPh3)](NO3), 2, and [Pd(apptsc)(PPh3)](NO3)•H2O, 3, where PPh3 = triphenylphosphine; Haptsc = 2-acetylpyridine-thiosemicarbazone; Hapmtsc = 2-acetylpyridine-N(4)-methyl-thiosemicarbazone and Happtsc = 2-acetylpyridine-N(4)-phenyl-thiosemicarbazone. All complexes were characterized by elemental analysis, IR, UV-Vis, 1H and 31P{1H} NMR spectroscopies, and had their crystalline structures determined by X-ray diffractometry from single crystals. The monoanionic thiosemicarbazonate ligands act in a tridentate mode, binding to the metal through the pyridine nitrogen, the azomethine nitrogen and the sulfur atoms. The cytotoxic activity against the breast cancer cell line MDA-MB231 and the anti-Mycobacterium tuberculosis H37Rv ATCC 27294 activity were evaluated for the compounds. All PdII complexes were highly active against the studied cell line, presenting similar values of IC50, around 5 µmol L-1, while the clinically applied antitumor agent cisplatin was inactive. The compounds show remarkable anti-M. tuberculosis activities, presenting MIC values comparable or better than some commercial anti-M tuberculosis drugs.FAPESPCAPESCNPqFINE