Decreased immune response in undernourished rats after air pollution exposure.

Children are highly vulnerable subpopulation to malnutrition and air pollution. We investigate, in a rat nutritional growth retardation (NGR) model, the impact of Residual Oil Fly Ash (ROFA) on the lung immune response using in vitro and ex vivo methods. In vitro: Alveolar macrophages (AM) were isolated from Control (C) and NGR animals, cultured and treated with ROFA (1-100 µg/ml) for 24 h. Ex vivo: C and NGR rats were intranasally instilled with ROFA (1 mg/kg BW) or PBS. 24 h post-exposure AM were isolated and cultured. ROFA-treatment increased superoxide anion production and TNFα secretion in C-AM in vitro, though for NGR-AM this response was lower. A similar pattern was observed for TNFα and IL-6 secretion in ex vivo experiments. Regarding the antioxidant response, although NGR-AM showed increased Nrf2, after ROFA instillation an attenuated activation was observed. To conclude, chronic undernutrition altered AM response to ROFA affecting immune responsiveness to air pollutants.

Mechanical mandible competence in rats with nutritional growth retardation.

OBJECTIVE: In order to provide a better understanding of the sympathetic nervous system as a negative regulator of bone status, the aim of the study was to establish the biomechanical mandible response to different doses of a ß-adrenergic antagonist such as propranolol (P) in a stress-induced food restriction model of growth retardation. METHODS: Rats were assigned to eight groups: Control (C), C+P3.5 (CP3.5), C+P7 (CP7), C+P14 (CP14), NGR, NGR+P3.5 (NGRP3.5), NGR+P7 (NGRP7) and NGR+P14 (NGRP14). C, CP3.5, CP7 and CP14 rats were freely fed with the standard diet. NGR, NGRP3.5, NGRP7 and NGRP14 rats received, for 4 weeks (W4), 80% of the amount of controls food consumed. Propranolol 3.5, 7 and 14mg/kg/day was injected ip 5days per week in CP3.5 and NGRP3.5, CP7 and NGRP7, CP14 and NGRP14, respectively. At W4, zoometry, mandible morphometry, static histomorphometric and biomechanical competence were performed. RESULTS: A dose of Propranolol 7mg/kg/day induced interradicular bone volume accretion reaching a mandible stiffness according to chronological age. CONCLUSION: These findings evidenced that sympathetic nervous system activity is a negative regulator of mandible mechanical competence in the nutritional growth retardation model. Propranolol 7mg/kg/day, under the regimen usage, seems to be appropriate to blockade SNS activity on mandible mechanical performance in NGR rats, probably associated to an effect on bone mechanostat system ability to detect disuse mode as an error.

[Operational mechanism modification of bone mechanostat in an animal model of nutritional stress: effect of propranolol]. / Modificación del mecanismo operacional del mecanostato óseo en un modelo de estrés nutricional por efecto del propranolol.

INTRODUCTION: Propranolol (P) treatment exerts a preventive effect against the detrimental consequences to bone status in mildly chronically food-restricted growing rats (NGR) by an increment in cortical bone and by improving its spatial distribution. OBJECTIVE: To study the effect of beta-blocker on operational mechanism of bone mechanostat in an animal model of nutritional stress. MATERIAL AND METHODS: Weanling male Wistar rats were randomly assigned to four groups: control (C), C + P (CP), NGR and NGR + P (NGRP). C and CP rats were fed freely with the standard diet. NGR and NGRP rats received, for 4 weeks, 80% of the amount of food consumed by C and CP respectively, the previous day, corrected by body weight. Propranolol (7 mg/kg/day) was injected ip 5 days per week, for four weeks in CP and NGRP rats. C and NGR received saline injections at an identical dosage regimen. Body weight and length were determined during the experimental period. Dietary intake was registered daily. Animals were sacrificed after 4 weeks of food restriction. Immediately, cuadriceps, femur and tibiae from each animal were dissected and weighed, and histomorphometric and mechanical studies were performed. Serum a-CTX, osteocalcin, intact PTH, calcium and phosphorous were determined. Body protein (% prot) was measured in all groups. RESULTS: Food restriction induced detrimental effects on body and femoral growth, load-bearing capacity (Wf), % prot and cuadriceps weight in NGR us. C (p < 0.01). beta-blocker did not modify anthropometric and bone morphometric parameters in NGRP and CP us. NGR and C, respectively (p > 0.05). However, Wf NGRP vs. NGR was significantly higher (p < 0.01). alpha-CTX was significantly higher in NGR vs. C (p < 0.01). No significant differences were observed in alpha-CTX levels between CP, NGRP and C (p > 0.05). Serum osteocalcin, intact PTH, calcium and phospho- rous showed no significant difference between groups (p > 0.05). CONCLUSION: These results suggest that modeling increase in bone mass and strength in NGRP rats could be due to an anticatabolic interaction of the beta-blocker propranolol on operational mechanism of bone mechanostat in an animal model of nutritional stress.

[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.

[Neuronal LHRH system activity in an animal model of growth retardation]. / Actividad del sistema neuronal LHRH en un modelo animal de retraso del crecimiento.

OBJECTIVE: Mild and chronic energy restriction results in growth retardation with puberal delay, a nutritional disease known as nutritional dwarfing (ND). The aim of the present study was to assess the profile of hypothalamic luteinizing hormone-releasing hormone (LHRH) release, at baseline and under glutamate stimulation, in ND rats to elucidate gonadotrophic dysfunction. Reproductive ability during refeeding was also studied. MATERIAL AND METHODS: At weaning, 60 male rats were assigned to two groups of 30 animals each: a control and an experimental group. Control rats were fed ad libitum with a balanced rodent diet. The experimental group received 80% of the diet consumed by the control group for 4 weeks. After 4 weeks of food restriction, the ND group was fed freely for 8 weeks. Ten rats from each group were sacrificed every 4 weeks for assays. RESULTS: At week 4, body weight and length were significantly diminished in the experimental group vs. the control group (p<0.001). No changes were observed in LHRH baseline release, pulse frequency or amplitude in the experimental group compared with the control group at any time. However, under glutamate stimulation, LHRH release was significantly higher in ND rats than in control rats at week 4 (p<0.05). Refeeding the ND group allowed the rats to reach overall growth and reproductive ability. CONCLUSIONS: The results of the present study suggest that the response to the facilitatory effect of glutamate on LHRH release in post-restricted ND rats is probably related to a lesser central nervous system maturation in relation to their chronological age. The adequate somatic growth and normal reproductive ability attained with refeeding suggest the reversibility of the two energetically costly processes compromised by global, mild and chronic food restriction.

Evaluación del crecimiento normal en ratas a través del puntaje Z / Normal growth pattenrs in rats, by Z score

La desnutrición infantil es una de las causas más importantes del retardo del crecimiento. Los métodos antropométricos son de sumo valor diagnóstico en la clínica pediátrica para la evaluación del estado nutricional y para el monitoreo de su evolución. En estudios previos, hemos demostrado que el crecimiento de la rata se ajustó a patrones de distribución semejantes a los observados en niños clínicamente sanos. Sin embargo, es necesario interpretar la información antropométrica por medio de un tratamiento estadístico que se ajusta a una distribución de variables normales y no normales. Se estudiaron 100 ratas (50 machos y 50 hembras) de cepa wistar, desde el destete (25 días, peso = 3040 g) hasta los 70 días de edad. Se alimentaron con una dieta balanceada para roedores y agua en condiciones de libre demanda. El peso y la talla se determinaron con una frecuencia de 2 y 4 días, respectivamente. Se confeccionaron las curvas percentilares de peso y talla en función de la edad y peso en función de la talla, para ambos sexos. El criterio estadístico aplicado fue el puntaje Z (número de desviaciones estándares respecto a la mediana) y se calculó de cauerdo a Z = ( mediana-valor del sujeto en estudio/desviación estándar de la mediana). Las categorías antropométricas fueron similares a las obtenidas en niños. Estas evidencias sugieren que la rata en crecimiento podría ser utilizada en diseños experimentales para predecir e inferir la respuesta en niños