Efecto de diferentes dosis de propranolol sobre la eficiencia estructural y mecánica esquelética en un modelo animal de retraso del crecimiento / Effect of different propranolol doses on skeletal structural and mechanic efficiency in an animal model of growth retardation

Objetivo Evaluar en un modelo de retraso del crecimiento (enanismo por desnutrición [ED]) el efecto de diferentes dosis de propranolol (P) sobre las variables antropo-morfométricas y biomecánicas del esqueleto apendicular. Materiales y métodos Ratas macho Wistar de 21 días se dividieron en grupos: control (C), C+P3,5 (CP3,5); C+P7 (CP7); C+P10,5 (CP10,5); C+P14 (CP14); ED, ED+P3,5 (EDP3,5); ED+P7 (EDP7); ED+P10,5 (EDP10,5) y ED+P14 (EDP14). Los animales controles con/sin P recibieron una dieta para roedores ad libitum; las ratas ED con/sin P recibieron por cada 100 g de peso corporal un 80% de la misma dieta durante 4 semanas (T4). Propranolol 3,5; 7; 10,5 y 14mg/kg/día fue inyectado intraperitonealmente 5 días/semana durante 4 semanas en CP3,5 y EDP3,5; CP7 y EDP7; CP10,5 y EDP10,5 y CP14 y EDP14, respectivamente. Resultados A T4, la restricción energética produjo efectos negativos sobre el crecimiento global, el fémur y su competencia mecánica. Propranolol mejoró la rigidez ósea en los animales ED con dosis de 7 y 10,5mg/kg/día, con un máximo de respuesta a 7mg/kg/día. Conclusiones El propranolol 7mg/kg/día sería la dosis más efectiva en la incorporación modelatoria de hueso con incremento de su eficiencia estructural y mecánica en el presente modelo animal de retraso del crecimiento. Dicho efecto podría ser el resultado del mantenimiento de la viabilidad del mecanosensor, de modificaciones de su sensibilidad, del punto de referencia biomecánico y/o de la respuesta de los efectores en las ratas ED(AU)

Objective To assess in a growth retardation (GR) model the impact of different propranolol (P) doses on anthropomorphometric and biomechanical variables of the appendicular skeleton. Materials and methods Twenty-one day-old male Wistar rats were divided into the following groups: control (C), C+P3.5 (CP3.5); C+P7 (CP7); C+P10.5 (CP10.5); C+P14 (CP14); ED, ED+P3.5 (EDP3.5); ED+P7 (EDP7); ED+P10.5 (EDP10.5), and ED+P14 (EDP14). Control animals with/without P were fed a rodent diet ad libitum. GR rats with/without P were given 80% of the same diet per 100g body weight for 4 weeks (T4). Propranolol 3.5, 7, 10.5, and 14mg/kg/day was intraperitoneally injected 5 days/week for 4 weeks to the CP3.5 and EDP3.5; CP7 and EDP7; CP10.5 and EDP10.5, and CP14 and EDP14 groups respectively. Results At T4, energy restriction had negative effects upon overall growth, femur, and its mechanical competence. Propranolol improved bone rigidity in GR animals at doses of 7 and 10.5mg/kg/day, with a maximum response at 7mg/kg/day. Conclusions Propranolol 7mg/kg/day would be the most effective dose for modeling incorporation of bone, as shown by the increased skeletal structural and mechanic efficiency in this animal model of growth retardation. Such effect may result from maintenance of mechanosensor viability, changes in its sensitivity, the biomechanical reference point and/or effector response in GR rats(AU)

[Effect of different propranolol doses on skeletal structural and mechanic efficiency in an animal model of growth retardation]. / Efecto de diferentes dosis de propranolol sobre la eficiencia estructural y mecánica esquelética en un modelo animal de retraso del crecimiento.

OBJECTIVE: To assess in a growth retardation (GR) model the impact of different propranolol (P) doses on anthropomorphometric and biomechanical variables of the appendicular skeleton. MATERIALS AND METHODS: Twenty-one day-old male Wistar rats were divided into the following groups: control (C), C+P3.5 (CP3.5); C+P7 (CP7); C+P10.5 (CP10.5); C+P14 (CP14); ED, ED+P3.5 (EDP3.5); ED+P7 (EDP7); ED+P10.5 (EDP10.5), and ED+P14 (EDP14). Control animals with/without P were fed a rodent diet ad libitum. GR rats with/without P were given 80% of the same diet per 100g body weight for 4 weeks (T4). Propranolol 3.5, 7, 10.5, and 14 mg/kg/day was intraperitoneally injected 5 days/week for 4 weeks to the CP3.5 and EDP3.5; CP7 and EDP7; CP10.5 and EDP10.5, and CP14 and EDP14 groups respectively. RESULTS: At T4, energy restriction had negative effects upon overall growth, femur, and its mechanical competence. Propranolol improved bone rigidity in GR animals at doses of 7 and 10.5mg/kg/day, with a maximum response at 7 mg/kg/day. CONCLUSIONS: Propranolol 7 mg/kg/day would be the most effective dose for modeling incorporation of bone, as shown by the increased skeletal structural and mechanic efficiency in this animal model of growth retardation. Such effect may result from maintenance of mechanosensor viability, changes in its sensitivity, the biomechanical reference point and/or effector response in GR rats.

Aluminum bone toxicity in immature rats exposed to simulated high altitude.

Aluminum (Al) is an element to which humans are widely exposed. Chronic administration induces a negative effect on bone tissue, affecting collagen synthesis and matrix mineralization. Its toxic effects are cumulative. Hypobaric hypoxia induces stress erythropoiesis, leading to hypertrophy of the erythropoietic marrow affecting the bone. This study was designed to evaluate the risk of Al bone toxicity among immature rats maintained at simulated high altitude (SHA) by mechanical assessment of stiffness and strength, calculation of some indicators of bone material and geometrical properties, as well as blood determinations. Forty growing rats were divided into control and experimental groups whether injected with vehicle or Al, as Al(OH)(3), three times a week for 3 months. Half of each group was exposed to hypobaric conditions (HX) by placing the animals in a SHA chamber. Both treatments negatively affected structural properties of bones, decreasing the maximum capacity to withstand load, the limit elastic load and the capacity of absorbing energy in elastic conditions. Al administration significantly depressed mandible structural stiffness, although diaphyseal stiffness was not modified. Indicators of bone material intrinsic properties, elastic modulus and stress, were significantly reduced by Al or HX. Treatments increased the diaphyseal sectional bending moment of inertia, suggesting that femur, but not mandible, compensates for the decline in the material properties with an adaptation of its architecture to maintain structural properties. The different biomechanical behaviors between the two kinds of bone are probably due to their different embryological origin and specific functions, as mandible is a bone that adjusts its strength to biting forces, whereas femur is designed to support load.