ES2239541A1 - Anabolic steroids action enhancement by e.g. arginine supplements comprises controlled addition of salts and mixtures for use on animals and humans - Google Patents
Anabolic steroids action enhancement by e.g. arginine supplements comprises controlled addition of salts and mixtures for use on animals and humansInfo
- Publication number
- ES2239541A1 ES2239541A1 ES200400619A ES200400619A ES2239541A1 ES 2239541 A1 ES2239541 A1 ES 2239541A1 ES 200400619 A ES200400619 A ES 200400619A ES 200400619 A ES200400619 A ES 200400619A ES 2239541 A1 ES2239541 A1 ES 2239541A1
- Authority
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- Spain
- Prior art keywords
- arginine
- anabolic
- testosterone
- use according
- mixtures
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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Abstract
Description
Potenciación de las acciones anabolizantes de los compuestos esteroideos por suplementos de arginina y/o sus precursores.Enhancement of anabolic actions of Steroid compounds by arginine supplements and / or their precursors
La invención se refiere al uso de compuestos para incrementar o modificar la masa muscular de un animal, especialmente para potenciar la acción de anabolizantes, y composiciones para tal fin.The invention relates to the use of compounds for increase or modify the muscle mass of an animal, especially to boost anabolic action, and Compositions for this purpose.
Los andrógenos son responsables del fenotipo masculino y de la regulación del crecimiento y diferenciación de diferentes tejidos extragenitales (Bardin y Catterall 1981). Los mecanismos moleculares por los que los andrógenos producen todos estos efectos no se conocen completamente (Sheffield-More 2000; Verhoeven and Swinnem 1999). Aunque se ha postulado que la unión de la hormona a su receptor en los tejidos diana es la responsable de los efectos a nivel génico producidos por la misma, otros factores como hormonas hipofisarias, factores de crecimiento tipo insulina, o otros moduladores de la fosforilación de proteínas pueden participar en la regulación de las acciones de los andrógenos (Brikman et al 1999; Jansson et al 1985; Hobbs et al 1993; Urban et al 1995.).Androgens are responsible for the male phenotype and the regulation of growth and differentiation of different extragenital tissues (Bardin and Catterall 1981). The molecular mechanisms by which androgens produce all these effects are not fully known (Sheffield-More 2000; Verhoeven and Swinnem 1999). Although it has been postulated that the binding of the hormone to its receptor in the target tissues is responsible for the effects at the gene level produced by it, other factors such as pituitary hormones, insulin-like growth factors, or other phosphorylation modulators of Proteins can participate in the regulation of the actions of androgens (Brikman et al 1999; Jansson et al 1985; Hobbs et al 1993; Urban et al 1995.).
El crecimiento tisular está controlado por interacciones complejas de factores hormonales, genéticos y nutricionales, entre estos últimos los aminoácidos tienen un papel importante en la regulación de los genes implicados en el control del crecimiento corporal (Fafournoux et al 2000).Tissue growth is controlled by complex interactions of hormonal, genetic and nutritional factors, among the latter amino acids have an important role in the regulation of genes involved in the control of body growth (Fafournoux et al 2000).
El incremento de la masa muscular tiene interés en la cría de animales, por ejemplo para aumentar el rendimiento físico o la producción de carne.The increase in muscle mass is of interest in animal husbandry, for example to increase yield Physical or meat production.
En el caso de humanos tiene interés para el tratamiento y recuperación de pacientes con atrofias, distrofias o pérdida de masa muscular, por ejemplo después de lesiones o intervenciones quirúrgicas o como consecuencia de la edad. También tiene aplicación en personas sanas como es el caso de deportistas que quieran aumentar capacidad.In the case of humans, he is interested in treatment and recovery of patients with atrophies, dystrophies or loss of muscle mass, for example after injuries or surgical interventions or as a consequence of age. Too It has application in healthy people such as athletes Who want to increase capacity.
La patente española ES 2096524 describe el uso de la Ngmonometil-l-arginina, para aumentar la capacidad de hacer ejercicio físico.Spanish patent ES 2096524 describes the use of Ngmonomethyl-l-arginine, for Increase the ability to exercise.
La solicitud de patente internacional WO 01 92330 describe el uso de la proteína ACRP30 para aumentar la masa muscular en pacientes o en personas sanas.International patent application WO 01 92330 describes the use of ACRP30 protein to increase mass muscle in patients or healthy people.
En ambos casos se trata de productos de difícil obtención. Aún subsiste la necesidad de proporcionar una composición con el efecto deseado sobre la masa muscular y que sea de fácil administración y producción.In both cases it is difficult products obtaining. There is still a need to provide a composition with the desired effect on muscle mass and make it Easy administration and production.
El objeto de esta invención es proporcionar una composición que aumente la masa muscular en un animal.The object of this invention is to provide a composition that increases muscle mass in an animal.
Sorprendentemente, hemos encontrado que la arginina y/o sus aminoácidos precursores (ornitina, citrulina y glutamina) potencian a nivel muscular los efectos anabólicos de un anabolizante (esteroideo).Surprisingly, we have found that the arginine and / or its precursor amino acids (ornithine, citrulline and glutamine) enhance the anabolic effects of a muscle level anabolic (steroidal).
Por lo tanto, se pueden emplear dichos compuestos (arginina y/o sus precursores + anabolizante esteroideo) en el tratamiento de pacientes con sepsis, traumas, quemaduras severas, SIDA y otras patologías que cursan con pérdidas severas de masa muscular y/o individuos sanos (deportistas, culturistas, etc.) para aumentar la masa muscular y/o para la recuperación muscular de dichos individuos.Therefore, said compounds can be used (arginine and / or its precursors + steroid anabolic) in the treatment of patients with sepsis, trauma, severe burns, AIDS and other pathologies that occur with severe mass losses muscle and / or healthy individuals (athletes, bodybuilders, etc.) to increase muscle mass and / or for muscle recovery from such individuals.
Por lo tanto en un aspecto la invención comprende el empleo de un compuesto seleccionado entre arginina, ornitina, citrulina, glutamina y sus mezclas en la elaboración de una composición para potenciar, en un animal, la acción anabólica de un anabolizante administrado de forma conjunta o separada a dicho animal.Therefore in one aspect the invention comprises the use of a compound selected from arginine, ornithine, citrulline, glutamine and mixtures thereof in the preparation of a composition to enhance, in an animal, the anabolic action of a anabolic agent administered together or separately to said animal.
En otro aspecto la invención comprende el empleo de un compuesto seleccionado entre arginina, sus precursores y sus mezclas junto con un anabolizante esteroideo, preferentemente testosterona, en la preparación de un kit para el tratamiento de patologías que cursen con alteraciones del metabolismo de la arginina.In another aspect the invention comprises the use of a compound selected from arginine, its precursors and its mixtures together with a steroid anabolic, preferably testosterone, in the preparation of a kit for the treatment of pathologies that occur with alterations in the metabolism of the arginine
En un tercer aspecto, la invención comprende el empleo de un compuesto seleccionado entre arginina, ornitina, citrulina, glutamina y sus mezclas en la elaboración de una composición para aumentar o recuperar la masa muscular de un animal, en combinación con un anabolizante administrado de forma conjunta o separada a dicho animal.In a third aspect, the invention comprises the use of a compound selected from arginine, ornithine, citrulline, glutamine and mixtures thereof in the preparation of a composition to increase or recover the muscle mass of a animal, in combination with an anabolic form administered joint or separate to said animal.
L- Arginina es un aminoácido que participa en la regulación de múltiples procesos bioquímicos en los mamíferos. Además de estar implicada en el ciclo de la urea y la síntesis de proteínas, sirve como precursor de la síntesis de aminoácidos, oxido nítrico, poliaminas, creatinina, agmatina y otros compuestos de tipo guanidino (Morris 1992; Morris 2002; Reyes et al 1994; Wu and Morris 1998; Barbul 1986).L- Arginine is an amino acid that participates in the regulation of multiple biochemical processes in mammals. In addition to being involved in the urea cycle and protein synthesis, it serves as a precursor to the synthesis of amino acids, nitric oxide, polyamines, creatinine, agmatine and other guanidine-type compounds (Morris 1992; Morris 2002; Reyes et al 1994 ; Wu and Morris 1998; Barbul 1986).
En la mayoría de los mamíferos la arginina es considerada un aminoácido no esencial en individuos sanos adultos, ya que puede ser sinterizada en las células tubulares de riñón a partir de la citrulina generada a nivel intestinal (Dahanakati et al 1990). Sin embargo arginina puede considerarse un aminoácido esencial en mamíferos adultos en determinadas condiciones, así como en animales jóvenes o durante el crecimiento, cuando la síntesis endógena es inadecuada para los requerimientos titulares (Rose et al 1954; Visek 1986; Cynober et al 1995; Wu y Meininger 2002). Además, se ha demostrado que suplementos de arginina en la dieta pueden ser beneficiosos ya que este aminoácido acelera el proceso de cicatrización de heridas, estimula al sistema inmunitario, aumenta el anabolismo proteico y puede mejorar a los pacientes con alteraciones cardiovasculares (Barbul 1986; Cui et al 1999; Shi et al 2000; Adjei et al 1995).In most mammals, arginine is considered a non-essential amino acid in healthy adult individuals, since it can be sintered in tubular kidney cells from citrulline generated at the intestinal level (Dahanakati et al 1990). However, arginine can be considered an essential amino acid in adult mammals under certain conditions, as well as in young animals or during growth, when endogenous synthesis is inadequate for the headline requirements (Rose et al 1954; Visek 1986; Cynober et al 1995; Wu and Meininger 2002). In addition, it has been shown that dietary arginine supplements can be beneficial since this amino acid accelerates the wound healing process, stimulates the immune system, increases protein anabolism and can improve patients with cardiovascular disorders (Barbul 1986; Cui et al 1999; Shi et al 2000; Adjei et al 1995).
Los niveles de arginina en plasma están regulados por la arginina de la dieta, el turnover de proteínas, transporte, síntesis y catabolismo de arginina. La importancia relativa de estos procesos depende de diversos factores tales como la edad, especie o contenido de sal en la dieta. (Cynober et al 1995; Visek 1986; Kitiyakara et al 2001; Boger and Bode-Boger 2001). Mientras, la síntesis de arginina endógena tiene un papel importante en la regulación de la homeostasis de este aminoácido en algunos mamíferos durante el periodo neonatal y el crecimiento, el contenido de arginina en la dieta parece ser el principal regulador de los niveles de arginina en humanos (Wu and Knabe 1995; Castillo et al 1994). En roedores, se ha demostrado que la alimentación de animales adultos con una dieta deficiente en arginina disminuye sus concentraciones plasmáticas (Gross et al 1991). En un estudio reciente, nosotros hemos encontrado que en los ratones existe un marcado dimorfismo en los niveles de arginina en plasma, riñón y músculo esquelético, teniendo unos niveles más altos las hembras que los machos (Ruzafa et al 2003).Arginine levels in plasma are regulated by diet arginine, protein turnover, transport, synthesis and arginine catabolism. The relative importance of these processes depends on various factors such as age, species or salt content in the diet. (Cynober et al 1995; Visek 1986; Kitiyakara et al 2001; Boger and Bode-Boger 2001). While, the synthesis of endogenous arginine has an important role in the regulation of homeostasis of this amino acid in some mammals during the neonatal period and growth, the content of arginine in the diet seems to be the main regulator of arginine levels in humans (Wu and Knabe 1995; Castillo et al 1994). In rodents, feeding of adult animals with an arginine-deficient diet has been shown to decrease their plasma concentrations (Gross et al 1991). In a recent study, we have found that in mice there is a marked dimorphism in arginine levels in plasma, kidney and skeletal muscle, females having higher levels than males (Ruzafa et al 2003).
La presente invención demuestra la relación existente entre las acciones anabólicas producidas por un anabolizante como la testosterona a nivel muscular y su dependencia con las concentraciones de arginina en plasma. Tanto una disminución de arginina producida por restricción de este aminoácido en la dieta como una disminución de su síntesis endógena debida a una insuficiencia renal tienen capacidad para inhibir las acciones anabólicas de testosterona a nivel muscular.The present invention demonstrates the relationship existing among the anabolic actions produced by a anabolic as testosterone at the muscular level and its dependence with plasma arginine concentrations. Both a decrease in arginine produced by restriction of this amino acid in the diet as a decrease in its endogenous synthesis due to a renal failure have the capacity to inhibit actions Anabolic testosterone level muscle.
Por lo tanto el empleo de citrulina, ornitina, glutamina o arginina asociadas a testosterona u otros anabolizantes en tratamientos de pacientes con quemaduras severas, sepsis, traumas u otras patologías donde se sepa que existen alteraciones del metabolismo de esta aminoácido y requieran tratamiento con anabolizantes potencia la acción de dichos anabolizantes. El uso de esta asociación también será útil par potenciar las acciones anabólicas de testosterona y otros anabolizantes en deportistas y culturistas. Finalmente tiene interés en el caso de animales para incrementar la producción de carne.Therefore the use of citrulline, ornithine, glutamine or arginine associated with testosterone or other anabolic agents in treatments of patients with severe burns, sepsis, traumas or other pathologies where it is known that there are alterations of the metabolism of this amino acid and require treatment with Anabolic agents enhances the action of these anabolic agents. The use of this association will also be useful to enhance the actions Testosterone and other anabolic anabolics in athletes and bodybuilders Finally, he has an interest in the case of animals for Increase meat production.
Así pues en un aspecto la invención consiste en el empleo de un compuesto seleccionado entre arginina, ornitina, citrulina, glutamina, sus sales y sus mezclas en la elaboración de una composición para potenciar, en un animal, la acción anabólica de un anabolizante administrado de forma conjunta o separada a dicho animal.Thus, in one aspect the invention consists in the use of a compound selected from arginine, ornithine, citrulline, glutamine, its salts and mixtures in the preparation of a composition to enhance anabolic action in an animal of an anabolic agent administered together or separately to said animal.
En otro aspecto la invención comprende el empleo de un compuesto seleccionado entre arginina, sus sales, sus precursores y sus mezclas junto con un anabolizante esteroideo, preferentemente testosterona, en la preparación de un kit para el tratamiento de patologías que cursen con alteraciones del metabolismo de la arginina. Detalles sobre la forma y administración del anabolizante y la arginina o sus precursores se comentan más adelante.In another aspect the invention comprises the use of a compound selected from arginine, its salts, its precursors and their mixtures together with a steroidal anabolic, preferably testosterone, in the preparation of a kit for the treatment of pathologies that occur with alterations of the Arginine metabolism. Details on the form and administration of anabolic and arginine or its precursors are discussed more ahead.
En un tercer aspecto, la invención comprende el empleo de un compuesto seleccionado entre arginina, ornitina, citrulina, glutamina, sus sales y sus mezclas en la elaboración de una composición para aumentar o recuperar la masa muscular de un animal, en combinación con un anabolizante administrado de forma conjunta o separada a dicho animal.In a third aspect, the invention comprises the use of a compound selected from arginine, ornithine, citrulline, glutamine, its salts and mixtures in the preparation of a composition to increase or recover the muscle mass of a animal, in combination with an anabolic form administered joint or separate to said animal.
En una variante, el animal es un humano. En este caso puede ser un individuo sano (deportista o culturista) con el fin de aumentar su masa muscular. Los anabolizantes esteroideos presentan efectos secundarios y adversos. En este caso el uso de la arginina y sus precursores tiene la ventaja de potenciar la acción del anabolizante que podrá ser utilizado en concentraciones menores que si se administrara sólo.In a variant, the animal is a human. In this case can be a healthy individual (athlete or bodybuilder) with the In order to increase your muscle mass. Anabolic steroids They have side and adverse effects. In this case the use of the Arginine and its precursors have the advantage of enhancing the action of the anabolic that can be used in lower concentrations That if administered alone.
Alternativamente puede ser un paciente, para recuperar, modificar o aumentar su masa muscular. Por ejemplo un paciente con sepsis, traumas, quemaduras severas, síndrome de inmunodeficiencia adquirida, o condiciones patológicas que llevan asociada pérdida de masa muscular. También se puede tratar de un individuo con una concentración de arginina inferior a la de un individuo sano, por ejemplo como consecuencia un fallo renal.Alternatively it can be a patient, to recover, modify or increase your muscle mass. For example a patient with sepsis, trauma, severe burns, syndrome acquired immunodeficiency, or pathological conditions that lead Associated loss of muscle mass. It can also be a individual with an arginine concentration lower than that of a healthy individual, for example as a consequence a renal failure.
En otra variante se trata de un animal no humano,
para aumentar el rendimiento físico o para incrementar la
pro-
ducción de carne. La invención también permite reducir
la cantidad de anabolizantes esteroideos utilizada
habitualmente.In another variant it is a non-human animal, to increase physical performance or to increase the pro-
meat ducting The invention also allows reducing the amount of steroidal anabolic agents commonly used.
El anabolizante que se administra conjuntamente con la arginina, ornitina, citrulina, glutamina y sus mezclas puede ser administrado de forma subcutánea, intradermica, implantes cutáneos, intramuscular u oral.The anabolic agent that is co-administered With arginine, ornithine, citrulline, glutamine and their mixtures you can be administered subcutaneously, intradermally, implants cutaneous, intramuscular or oral.
De forma preferente el anabolizante es testosterona. En una variante la testosterona se administra en una cantidad comprendida entre 25 - 600 mg de esteres de testosterona de acción prolongada semanalmente durante 3, 6, 8, 10, 20 y 32 semanas. Oxandrolona se administra en una cantidad comprendida entre 5-80 mg día durante 3,6,8,10, 20 y 32 semanas.Preferably the anabolic is testosterone In a variant testosterone is administered in a amount between 25 - 600 mg of testosterone esters long-acting weekly for 3, 6, 8, 10, 20 and 32 weeks Oxandrolone is administered in an amount between 5-80 mg day for 3,6,8,10, 20 and 32 weeks.
Preferiblemente el anabolizante se administra a intervalos. El intervalo depende del anabolizante utilizado pudiendo ser desde 48h -7-15 y 30. Para los implantes cutáneos puede ser de más días.Preferably the anabolic is administered to intervals. The interval depends on the anabolic agent used. It can be from 48h-7-15 and 30. For skin implants can be more days.
La composición que comprende un compuesto seleccionado entre arginina, ornitina, citrulina, glutamina y sus mezclas se administra de forma preferente por vía oral. En una variante forma parte de una composición farmacéutica.The composition comprising a compound selected from arginine, ornithine, citrulline, glutamine and their Mixtures are preferably administered orally. In a variant is part of a pharmaceutical composition.
Para la administración se prefieren cantidades diarias de hasta 15 g de arginina o el equivalente de sus precursores. Los suplementos de aminoácidos pueden estar comprendidos entre 0.1- 0.6 g/kg día durante los mismos periodos de la administración de los anabolizantes.Amounts are preferred for administration daily up to 15 g of arginine or the equivalent of its precursors Amino acid supplements may be between 0.1-0.6 g / kg day during the same periods of Anabolic administration.
Se utilizaron ratones Swiss jóvenes y adultos de ambos sexos mantenidos a 21-22°C y con ciclos de luz-oscuridad de 12 horas. Los animales se alimentaron con dieta estándar y agua "ad libitum" excepto en los experimentos con dieta deficiente en arginina (ICN). Los animales se sacrificaron bajo anestesia con éter, obteniéndose la sangre por punción cardiaca, y los tejidos obtenidos se mantuvieron a -70°C hasta su análisis bioquímico. En todos los experimentos se cumplieron las normas del Real Decreto 223/1988 de 14 de marzo y la Orden del 13 de 1989 sobre protección de animales en la experimentación científica.Young and adult Swiss mice of both sexes maintained at 21-22 ° C and with cycles of light-darkness of 12 hours. The animals are fed with standard diet and water "ad libitum" except in the experiments with arginine deficient diet (ICN). The animals were sacrificed under anesthesia with ether, obtaining the blood by cardiac puncture, and the tissues obtained were maintained at -70 ° C until biochemical analysis. In all experiments, complied with the rules of Royal Decree 223/1988 of March 14 and the Order of 13 of 1989 on protection of animals in the scientific experimentation
Los ratones hembras fueron nefrectomizados bajo anestesia con pentobarbital sódico (80 mg/kg, i.p) mediante una incisión dorsal de la piel y el peritoneo, accediendo al riñón izquierdo y seccionándolo.Female mice were nephrectomized under anesthesia with sodium pentobarbital (80 mg / kg, i.p) using a dorsal incision of the skin and peritoneum, accessing the kidney left and sectioning it.
La influencia de arginina y citrulina en las acciones anabólicas de testosterona se estudió mediante la administración de un pienso deficiente en arginina (ICN) suplementando el agua de bebida con arginina o citrulina (1 al 5%). El tratamiento se mantuvo durante 20 días. En animales alimentados con pienso estándar también se suplementó con arginina o citrulina al 2-5% el agua de bebida.The influence of arginine and citrulline on Anabolic actions of testosterone was studied using the administration of an arginine deficient feed (ICN) supplementing drinking water with arginine or citrulline (1 to 5%). The treatment was maintained for 20 days. In fed animals with standard feed it was also supplemented with arginine or citrulline 2-5% drinking water.
Ratones Swiss CD1 de ambos sexos fueron tratados con propionato de testosterona (100mg/kg) mediante inyección subcutánea de la hormona disuelta en aceite de girasol. El tratamiento se realizó de forma crónica administrando la hormona cada 48 horas a lo largo de 15 o 20 días. Los animales controles fueron inyectados con vehículo sólo.Swiss CD1 mice of both sexes were treated with testosterone propionate (100mg / kg) by injection Subcutaneous hormone dissolved in sunflower oil. He treatment was performed chronically administering the hormone every 48 hours over 15 or 20 days. Control animals They were injected with vehicle only.
1. - Análisis de aminoácidos. La determinación de los aminoácidos plasmática y tisular se realizó por medio de un autoanalizador de aminoácidos Rank Hilger Chromaspeck, equipado con una columna de intercambio iónico y detector de fluorescencia. La derivatización post-columna de los aminoácidos se realizó por reacción con oftaldialdehido. Las muestras se desproteinizaron con ácido tricloroacético al 5% y Norleucina se utilizó como estándar interno.1. - Amino acid analysis . Plasma and tissue amino acids were determined by means of a Rank Hilger Chromaspeck amino acid autoanalyzer, equipped with an ion exchange column and fluorescence detector. Post-column derivatization of amino acids was performed by reaction with ophthalmicdehyde. The samples were deproteinized with 5% trichloroacetic acid and Norleucine was used as an internal standard.
2. - Determinación de testosterona. La determinación de esta hormona se realizó mediante un método inmunoenzimático (ELISA/ competición con tecnología de estreptavidina).2. - Determination of testosterone . The determination of this hormone was performed using an immunoenzymatic method (ELISA / competition with streptavidin technology).
La disponibilidad de arginina en el ratón depende de su capacidad biosintética del eje intestino-renal como del aporte de dicho aminoácido por la dieta. En la tabla 1 mostramos cómo la limitación de arginina de la dieta produce una clara disminución del peso corporal en los machos (10%) y del peso renal (22%), lo que determina una disminución del cociente entre el peso de los riñones (peso relativo renal) de aproximadamente un 15%. Este mismo tratamiento no afecta al peso corporal ni renal en las hembras.The availability of arginine in the mouse depends of its axis biosynthetic capacity intestine-renal as of the contribution of said amino acid For the diet. In table 1 we show how the limitation of Arginine from the diet produces a clear decrease in weight body weight in males (10%) and renal weight (22%), which determines a decrease in the ratio between the weight of the kidneys (relative renal weight) of approximately 15%. This same Treatment does not affect body or renal weight in females.
La deficiencia en arginina también produce una disminución significativa en las concentraciones plasmáticas y titulares de arginina en ambos sexos, mientras que únicamente produce una disminución significativa de ornitina y citrulina en las hembras (tabla 2) La alimentación con una dieta deficiente en arginina suplementada con 1% de arginina o citrulina revierte todos los cambios producidos por la deficiencia en arginina o citrulina revierte todos los cambios producidos por la deficiencia en arginina (datos no mostrados).Arginine deficiency also produces a significant decrease in plasma concentrations and Arginine holders in both sexes, while only produces a significant decrease in ornithine and citrulline in the females (table 2) Feeding on a diet deficient in arginine supplemented with 1% arginine or citrulline reverses all the changes produced by the deficiency in arginine or citrulline reverse all the changes produced by the deficiency in arginine (data not shown).
La tabla 3 muestra como la alimentación con una dieta deficiente en arginina suplementada con 1% de arginina o citrulina revierte todos los cambios producidos por la deficiencia en arginina.Table 3 shows how feeding with a Arginine deficient diet supplemented with 1% arginine or Citrulline reverses all the changes produced by the deficiency in arginine
Todos los datos obtenidos acerca de la influencia de la arginina de la dieta sobre el peso corporal y renal de los animales indican que este aminoácido ejerce un efecto anabolizante en el macho, lo que nos hizo pensar en una posible interacción entre arginina dietética y testosterona. En primer lugar especulamos con la posibilidad de que la arginina de la dieta pudiera estar disminuyendo la síntesis o liberación de testosterona por el testículo. Sin embargo la determinación de las concentraciones plasmáticas de testosterona entre machos y hembras con dieta conteniendo arginina o sin ella mostró que los niveles de testosterona, dentro de la gran variabilidad de este parámetro en ratón, no son afectados significativamente por la arginina de la dieta (7.1 \pm 2.4 ng/ml para los controles frente a 6.4 \pm 2.0 ng/ml para los machos deficientes en arginina).All data obtained about the influence of arginine from the diet on the body and renal weight of animals indicate that this amino acid exerts an anabolic effect in the male, which made us think of a possible interaction between dietary arginine and testosterone. First we speculate with the possibility that diet arginine could be decreasing the synthesis or release of testosterone by the testicle. However the determination of concentrations Testosterone plasma between males and females with diet containing or without arginine showed that the levels of testosterone, within the great variability of this parameter in mouse, are not significantly affected by the arginine of the diet (7.1 ± 2.4 ng / ml for controls versus 6.4 ± 2.0 ng / ml for males deficient in arginine).
La influencia de la arginina dietética sobre las acciones anabólicas de la testosterona fue estudiada mediante la administración de testosterona a ratones machos y hembras. La tabla 4 nos muestra como la arginina ejerce una clara influencia sobre el aumento del peso corporal y renal promovido por testosterona tanto en ratones machos como hembras. Tanto unos como otros, al ser alimentados con arginina y tratados con testosterona, aumenta significativamente su peso corporal y su peso renal. Estos resultados indican por tanto que la arginina exógena incrementa significativamente los efectos anabólicos de testosterona sobre el peso renal y corporal tanto en machos como en hembras. Esta tabla también nos muestra que la administración de testosterona y 1% de arginina o citrulina a animales alimentados con un pienso deficiente en arginina produce los mismos efectos anabólicos que los obtenidos cuando la testosterona fue dada a los animales alimentados con el pienso control.The influence of dietary arginine on Anabolic actions of testosterone was studied using the administration of testosterone to male and female mice. The board 4 shows us how arginine exerts a clear influence on the increased body and kidney weight promoted by testosterone both in male mice as females. Both ones and others, being fed with arginine and treated with testosterone, increases significantly your body weight and your renal weight. These results indicate therefore that exogenous arginine increases significantly the anabolic effects of testosterone on the renal and body weight in both males and females. This table it also shows us that the administration of testosterone and 1% of arginine or citrulline to animals fed with a feed Arginine deficient produces the same anabolic effects as those obtained when testosterone was given to animals fed with the control feed.
Hemos estudiado la influencia de la restricción de arginina en la hipertrofia renal compensatoria inducida por la nefrectomía unilateral. La tabla muestra que el incremento de la masa relativa renal después de 15 días de nefrectomía en ratones hembras alimentados con 1% o 0% de arginina fue de 27% y 19% respectivamente. La administración de testosterona, inmediatamente después de la nefrectomía produce un incremento muy significativo de la masa renal que alcanza en ambos grupos valores del 76% y 69% respectivamente. Esta tabla también nos muestra que el incremento relativo de la masa renal fue mayor cuando testosterona fue administrada quince días después de la nefrectomía independiente de la cantidad de arginina en la dieta. Sin embargo en los animales nefrectomizados la administración de testosterona únicamente produce un aumento del peso corporal cuando la arginina estaba presente en la dieta y la hormona se administro quince días después de la nefrectomía, no encontramos aumento del peso corporal cuando testosterona se administró inmediatamente después de la nefrectomía. Estos resultados obtenidos en animales nefrectomizados ponen de manifiesto que las acciones anabólicas de testosterona a nivel muscular también se van a ver alteradas cuando la síntesis de arginina endógena se vea comprometida como consecuencia de una disminución de la masa renal. Nuestros resultados también demuestran que esta falta de efecto a nivel muscular en los animales nefrectomizados es transitoria y limitada al periodo durante el cual tiene lugar los mecanismos de hipertrofia en el riñón remanente o se normalizan los niveles de arginina en plasma por mecanismo no clarificados.We have studied the influence of restriction of arginine in compensatory renal hypertrophy induced by unilateral nephrectomy. The table shows that the increase in relative renal mass after 15 days of nephrectomy in mice females fed 1% or 0% arginine was 27% and 19% respectively. Testosterone administration, immediately after nephrectomy produces a very significant increase of the renal mass that reaches 76% and 69% in both groups respectively. This table also shows us that the increase Relative renal mass was higher when testosterone was given fifteen days after independent nephrectomy of the amount of arginine in the diet. However in the nephrectomized animals administering testosterone only produces an increase in body weight when arginine was present in the diet and the hormone was administered fifteen days after nephrectomy, we found no increase in body weight when testosterone was administered immediately after nephrectomy These results obtained in animals nephrectomized show that the anabolic actions of testosterone at the muscular level will also be altered when the synthesis of endogenous arginine is compromised as consequence of a decrease in renal mass. Our results also show that this lack of effect at the level muscle in nephrectomized animals is transient and limited to the period during which the mechanisms of hypertrophy in the remaining kidney or normalization levels are normalized Arginine in plasma by mechanism not clarified.
En la tabla 6 puede observarse como cuando los animales son tratados con dosis farmacológicas de testosterona los efectos anabólicos máximos producidos por el andrógeno se obtienen con una concentración del 3% de arginina. Esta misma tabla nos muestra que los suplementos con arginina o citrulina a la hembra control en ausencia de testosterona no modifica el peso renal ni el corporal.Table 6 shows how when animals are treated with pharmacological doses of testosterone the maximum anabolic effects produced by androgen are obtained with a concentration of 3% arginine. This same table we shows that supplements with arginine or citrulline to the female control in the absence of testosterone does not modify the renal weight or the bodily.
Con la finalidad de comprobar si la interacción entre arginina y testosterona ocurría en otra especie, se realizaron una serie de experimentos en ratas Sprague Dawley hembras. Un grupo de ratas se trataron con testosterona a la misma dosis que la utilizada en ratones y a otro grupo se les administró la hormona asociado a 1% de citrulina en el agua de bebida. Los resultados obtenidos que mostramos en la tabla 7 demuestran que también en esta especie la arginina aumenta las acciones anabólicas producidas por testosterona.In order to check if the interaction between arginine and testosterone occurred in another species, it conducted a series of experiments on Sprague Dawley rats females A group of rats were treated with testosterone to it dose that was used in mice and another group was administered the hormone associated with 1% citrulline in drinking water. The results obtained that we show in table 7 show that also in this species arginine increases anabolic actions produced by testosterone.
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US5888553A (en) * | 1997-04-08 | 1999-03-30 | Infinity, Inc. | Non-steroidal anabolic composition |
US20030119888A1 (en) * | 1991-11-20 | 2003-06-26 | Allen Ann De Wees | Composition comprising l-arginine as a muscle growth stimulant and use thereof |
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US5726146A (en) * | 1994-12-06 | 1998-03-10 | Natural Supplement Association, Incorporated | Non-steroidal, anabolic dietary supplement and method to increase lean mass without linked increase fat mass |
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