Alteraciones histológicas hepáticas provocadas por la ingesta crónica de glutamato monosódico / Histological liver changes caused by chronic intake of monosodium glutamate

ntroducción. El glutamato es un aminoácido que está implicado en numerosas reacciones relacionadas con el metabolismo hepático, por lo que la sobreactivación de los receptores de glutamato por acción de la ingesta de glutamato monosódico (GMS) proveniente de la dieta, podría llevar a daño del tejido hepático. Este estudio se realizó con el objetivo de evaluar los cambios histológicos producidos en el hígado de ratas sometidas a la administración crónica de GMS. Metodología. Se trabajó con dos lotes de animales, uno experimental y otro control, cada uno de ellos constituido por seis ratas machos cepa Wistar de cinco semanas de edad. Al grupo experimental se le administró diariamente 0,1 g de queso de bajas calorías que contenía GMS monohidrato de 99% de pureza (grado alimentario puro), diluido en 50 µL de agua desionizada (0,3 g/100 g de peso corporal). Al grupo control se le administró la misma cantidad de sodio que el que contenía el GMS del grupo tratado, pero bajo la forma de NaCl. Al concluir el tratamiento, las ratas pertenecientes a ambos grupos se pesaron y sacrificaron, y se les extrajo el hígado para el estudio histológico. Se obtuvieron cortes histológicos que fueron coloreados con hematoxilina-eosina, PAS y coloración con tricrómico de Masson. El análisis de los cortes histológicos se llevó a cabo por observación directa en microscopio óptico con objetivo de 40x. Resultados. Se observó en general, conservación y apariencia normal de las características histológicas de los acinos hepáticos en el grupo control, en tanto que el hígado de las ratas tratadas con GMS presentó diferentes grados de degeneración hidrópica, cantidades variables de cuerpos hialinos eosinófilos, infiltración inflamatoria de células mononucleares y necrosis focal, principalmente en la zona 1 del acino hepático. Conclusión. Los resultados encontrados permiten aportar evidencias en torno a las alteraciones histopatológicas que la ingesta crónica de GMS provoca sobre el tejido hepático. Se recomienda alertar a la población para reducir la ingesta de alimentos que poseen GMS como saborizante.

Introduction. Glutamate is an amino acid that is involved in numerous reactions related to liver metabolism, so the overactivation of glutamate receptors due to the ingestion of monosodium glutamate (MSG) from the diet could lead to liver tissue damage. The aim of this study was to evaluate the histological changes produced in the liver of rats subjected to chronic administration of MSG. Methodology. Two sets of animals were used, an experimental and a control group, each consisting of six five-week-old Wistar male rats. The experimental group was administered 0.1 g of low-calorie cheese containing 99% purity MSG monohydrate (pure food grade) diluted in 50 µL of deionized water (0.3 g/100 g of weight) daily. The control group was administered the same amount of sodium as that contained in the MSG of the treated group, but in the form of NaCl. At the end of the treatment, the rats belonging to both groups were weighed and sacrificed, and their liver was removed for histological analysis. Histological sections were obtained and stained with hematoxylineosin, PAS and Masson's trichrome. The analysis of the histological sections was carried out by direct observation with an optical microscope and a 40x objective. Results. In general, conservation and normal appearance of the histological characteristics of the liver acini were observed in the control group, while the liver of the rats treated with MSG presented different degrees of hydropic degeneration, variable amounts of eosinophilic hyaline bodies, inflammatory infiltration of mononuclear cells and focal necrosis, that affected mainly zone 1 of the liver acinus. Conclusion. The results allow us to provide evidence about the histopathological alterations that the chronic intake of MSG causes on the liver tissue. It is recommended to alert the population to reduce the intake of foods that have GMS for flavoring.

Adverse effects in kidney function, antioxidant systems and histopathology in rats receiving monosodium glutamate diet.

We investigated the effects of adding of monosodium glutamate (MSG) to a standard diet on oxidative stress in kidney, nitric oxide excretion, renal ions handling and blood pressure. We examined the association of these changes with the effects on renal histology. The study was performed on male Wistar rats (5 weeks old) divided into 3 groups: 1) MSG group were fed a diet supplemented with 3g of MSG/kg b.w./day, five days a week, and spontaneous ingestion of a 1% MSG solution during 16 weeks; 2) NaCl group were fed a diet with NaCl (1g/kg b.w./day) and 0.35% NaCl solution permanently alone at the same frequency and time; 3) control group were fed the normal chow and tap water. Sodium, potassium, calcium, phosphorus, creatinine, protein and nitric oxide excretion were analyzed in urine. We utilized clearance techniques to examine glomerular filtration rate and cortical renal plasma flow. We determined the oxidative state and the histopathological changes of renal tissue. Following MSG treatment, absolute and fractional sodium and potassium excretion decreased although there was hyperfiltration. The MSG group showed similar increase in blood pressure than the NaCl group, but nitric oxide excretion was significantly reduced. Although no increase in lipid peroxidation was verified, its observed alteration in the reduced glutathione/oxidized cycle and their enzymes GPx and GR. These changes were accompanied by alterations histological both glomerular as well as tubular level and by interstitial fibrosis with mononuclear cells accumulation. These results indicate that the addition of MSG in the diet decreases the excretion of Na, K and water with hyperfiltration. NaCl retention that leads to hypertension was accompanied by renal pathologic changes, intrarenal oxidative stress and reduction of nitric oxide excretion.

Efecto de un herbicida a base de glifosato sobre la generación de alteraciones metabólicas sistémicas y cambios histológicos hepáticos en un modelo animal de insulinorresistencia / Effects of a glyphosate-based herbicide on systemic metabolic alterations and histologic hepatic changes present in an animal model of insulin resistance

Introducción: el estrés oxidativo y la inflamación asociados a la insulinorresistencia (IR) contribuyen a generar esteatohepatitis no alcohólica. También la exposición al glifosato, un herbicida ampliamente utilizado, incrementa la peroxidación lipídica hepática con aumento de radicales libres de O2. Objetivos: evaluar los efectos de la administración prolongada de un herbicida a base de glifosato sobre la generación de IR, estrés oxidativo y cambios histológicos hepáticos en animales tratados con una dieta rica en sacarosa (DRS). Metodología: ratas Wistar macho (~300 g) recibieron Credit® por vía intraperitoneal (~50 mg/kg de glifosato tres veces por semana; grupo G, n=6), sacarosa al 30% en el agua de bebida (grupo S, n=6), ambos tratamientos (grupo G+S, n=8), o ninguno de ellos (grupo C, n=7). Tras una exposición de 8-10 semanas se midieron glucemia e insulinemia basales y tras una carga de glucosa intraperitoneal. En la semana 13, tras la eutanasia, se extrajo el hígado (tinciones con hematoxilina-eosina y tricrómica de Masson, TBARS). Resultados: no hubo diferencias significativas en los niveles glucémicos basales o postcarga. Los tratamientos con G o S generaron incrementos leves de la IR evidenciados por el índice HOMA-IR, mientras que la combinación de G+S llevó a un aumento altamente significativo de este parámetro. También fue más marcado, en estos animales, el grado de lipoperoxidación (TBARS) medido en homogenatos hepáticos. La evaluación histológica mostró signos de esteatosis y fibrosis en los grupos G y G+S, e infiltrados inflamatorios en todos los grupos tratados. Conclusiones: aislado o en combinación con sacarosa, el herbicida a base de glifosato aumentó el grado de esteatosis y fibrosis a nivel hepático. Por otro lado, la administración del herbicida incrementó la magnitud de la insulinorresistencia inducida por la DRS generando un mayor estrés oxidativo a nivel hepático

Monosodium glutamate intake affect the function of the kidney through NMDA receptor.

AIMS: We investigated whether the chronic intake of monosodium glutamate (MSG) with food affects kidney function, and renal response to glycine. We also established if the NMDA receptors are involved in the changes observed. MAIN METHODS: Male Wistar rats (5weeks old) were fed a diet supplemented with MSG (3g/kg b.w./day), five days a week, and spontaneous ingestion of a 1% MSG solution during 16weeks. NaCl rats were fed a diet with NaCl (1g/kg b.w./day) and 0.35% NaCl solution at the same frequency and time. Control group was fed with normal chow and tap water. We utilized clearance techniques to examine glomerular filtration rate (GFR) and cortical renal plasma flow (CRPF) response to glycine and glycine+MK-801 (antagonist NMDA-R), and we determined NMDA-R1 in kidney by immunohistochemistry. KEY FINDINGS: The addition of MSG in the diet of rats increased both GFR and CRPF with an increase of absolute sodium reabsorption. However, hyperfiltration was accompanied with a normal response to glycine infusion. Immunostain of kidney demonstrate that the NMDA receptor is upregulated in rats fed with MSG diet. NMDA-R antagonist MK-801 significantly reduced both the GFR and CRPF; however the percentage of reduction was significantly higher in the group MSG. MK-801 also reduces fractional excretion of water, sodium and potassium in the three groups. SIGNIFICANCE: Renal NMDAR may be conditioned by the addition of MSG in the diet, favoring the hyperfiltration and simultaneously Na retention in the body.

Orchiectomy attenuates oxidative stress induced by aluminum in rats.

The aim of this work was to study whether the increase in antioxidant defenses associated with orchiectomy may account for the reduced susceptibility to aluminum (Al) in male kidney and also to examine whether the reduced antioxidant defenses are associated with androgen levels in orchiectomized (ORX) rats treated with testosterone propionate (TP). Rats were divided into nine groups, namely, intact males (without treatment, treated with sodium lactate, and treated with Al), sham males, ORX males (without treatment, treated with sodium lactate, treated with TP, treated with Al, and treated with TP and Al). Al groups were chronically treated with aluminum lactate for 12 weeks (0.575 mg Al/100 g of body weight, intraperitoneally, three times per week). We reported that ORX rats treated with Al had significantly less lipid peroxidation and an increased level of reduced glutathione (GSH) and GSH/oxidized glutathione ratio in the kidney when compared with intact and TP-treated ORX rats. The activity of superoxide dismutase, catalase, and glutathione peroxidase in ORX rats was much greater than in intact or TP-administered ORX rats. Castration reduced the glomerular alterations caused by Al as well as the number of necrotic tubular cells and nuclear abnormalities. However, we observed a slight alteration in brush border, dilation of proximal tubules, mononuclear infiltrates, and interstitial fibrosis. Castrated males treated with TP showed that this intervention cancels the protective effect of the ORX. This finding suggests that androgens contribute to the development of renal alterations and proteinuria in rats treated with Al. Our results showed that ORX rats are protected against the induction of oxidative stress by Al, but the morphological damage to the kidney tissue induced by the cation was only reduced. Male intact rats treated with Al had more severe glomerulosclerosis, tubular damage, and proteinuria than ORX rats.

Role of melatonin in the oxidative damage prevention at different times of hepatic regeneration.

The process of regenerating liver is the result of a balance between stimulating factors and inhibitors of hepatocyte proliferation. Melatonin and its metabolites have been found to protect tissues against oxidative damage generated by a variety of toxic agents and metabolic processes. Furthermore, studies in liver of rats showed a decrease in the liver mitochondrial hydroxylation of drugs returning to the normal state after the administration of antioxidants. This study was designed to determine, in experimental animals, whether the administration of an antioxidant agent such as melatonin could prevent cells events leading to tissue injury and hepatic dysfunction after partial hepatectomy (PH). Biliary flow (BF), oxidative stress in hepatic tissue and Na⁺/K⁺ ATPase activities in whole plasma membrane were determined. PH decreased the Na⁺/K⁺ ATPase activity. PH significantly reduced the BF (36%) and promoted oxidative stress with an increase of lipoperoxidation and decrease of glutathione peroxidase and catalase activities. Treatment with melatonin prevented the decrease of BF in rats with hepatectomy and normalized the Na⁺/K⁺ ATPase activity. Moreover, melatonin markedly attenuated oxidative stress produced by PH. This may be the results of the higher efficacy of melatonin in scavenging various free radicals and also because of its ability in stimulating the antioxidant enzymes. We suggest that oxidative stress before and during liver regeneration has a crucial role in cholestasis, apoptotic/necrotic hepatocellular damage and the impairment in liver transport function induced by PH and that melatonin could modulate the degree of oxidative stress and through it prevent the alterations in liver function carrier.

Melatonin prevents oxidative stress in ovariectomized rats treated with aluminium.

This study is designed to determine the simultaneous effect of aluminium (Al) and melatonin (Mel) treatment in intact and ovariectomized (Ovx) female rats on oxidative stress and their inter-organ relationship in the kidney and liver. Al-treated rats received an intra-peritoneal injection of solution of aluminium lactate (0.575 mg Al/100 g of body weight, three times a week), during 12 weeks. Mel groups received intra-peritoneal injections of melatonin at a dose of 10 mg/kg/day, 5 days/week, during 12 weeks. The results of this study showed that Al treatment in female rats modifies homeostasis of glutathione and the antioxidant capacity of the rat liver and kidney. The alteration of glutathione homeostasis and oxidative status was not associated with an increased lipid peroxidation in both organs with the exception of the increase observed in the liver of Ovx rats. Al also induced modifications in the activity of some enzymes related to the glutathione cycle: GSH-Px in the liver and kidney and glutathione reductase only in the kidney. Al exposure decreased CAT activity in both the kidney and liver of intact and Ovx groups. The administration of Mel in the intact and castrated females treated with Al seems to reduce oxidative changes in the liver and kidney of intact and Ovx rats.

Melatonin reduces oxidative damage induced by aluminium in rat kidney.

We evaluated the effect of melatonin (Mel), in male Wistar rats which received aluminium (Al) lactate for 12 weeks (0.57 mg Al/100g body weight (b.w.), i.p. three times per week). Moreover rats received Mel (10 mg/kg b.w. i.p. 5 days/weeks) for 12 weeks. At the end of the treatment water and sodium balances were studied, and nephrogenic cyclic adenosine monophosphate (cAMP) was also measured. Urinary osmolality was measured after the administration of desmopressin (vasopressin agonist) to assess concentrating capacity. Oxidative stress in renal tissue and Na(+)-K(+)ATPase and gamma-glutamyl transferase (GGT) activities in whole plasma membrane were determined. Sodium and water balances were impaired by Al. We found decreased urinary concentrating ability and nephrogenic cAMP excretion. Al increased the Na(+)-K(+)ATPase activity, and serum aldosterone concentration. Mel normalized serum aldosterone level, the Na(+)-K(+)ATPase activity and potassium urinary without improving water and sodium excretion. Mel treatment did not improve the impaired urinary concentrating ability. Al reduced the GGT activity, an effect that persists in Al(+) Mel. Al exposure promoted oxidative stress with an increase in lipid peroxidation (LPO), and a decrease in glutathione (GSH) and glutathione peroxidase (GSH-Px) and catalase (CAT) activities. Mel markedly attenuated oxidative stress produced by Al. This may result from the higher efficacy of melatonin in scavenging various free radicals and also because of its ability in stimulating the antioxidant enzymes. However, it only reduced some alterations in the renal functions particularly related to the water and sodium excretion, which would be independent of the increased production of reactive oxygen substances.

Study of iron homeostasis following partial hepatectomy in rats with chronic aluminum intoxication.

Effects of both chronic aluminum (Al) exposure and partial hepatectomy on iron (Fe) homeostasis were studied. Male Wistar rats were intraperitoneally administered either 27 mg Al/kg body weight (as aluminum hydroxide) or the vehicle saline, three times a week for 3 mo. After this time, half of the rats of each group was sham operated (SH) and the other half was partially hepatectomized (PH). Animals of the four experimental groups (vehicle+SH [SH]; Al+SH; vehicle+PH [PH], and Al+PH) were killed 48 h after the surgical procedure. Serum, hepatic, and intestinal Al levels were found to be increased both for Al+SH and Al+PH. The serum Fe concentration and transferrin saturation percentage were significantly diminished in the rats of the Al+PH group, thus showing interaction between Al administration and PH. The 59Fe mucosal-to-serosal transport, studied in the intestinal loop in situ, was not affected by Al or PH. The malregulation of intestinal Fe absorption in Al exposure and/or PH when the serum Fe concentration was diminished could be the result of the increased lipid peroxidation (thiobarbituric acid-reactive substances [TBARS]) observed in this tissue. Mucosal TBARS were increased by Al exposure (+26%) and PH (+37%) and interaction between Al and PH was observed (+44%). These results show that when liver surgery is performed after prolonged Al exposure, it leads to impairment of Fe homeostasis. We underline the importance of the exposure to Al, a potentially toxic element, in the study of risk assessment in patients who must be submitted to major liver resection.

Study of hemorheological parameters following partial hepatectomy in rats with chronic aluminium intoxication.

The aim of our work was to analyze the hemorheological parameters following partial hepatectomy in rats with chronic Al-intoxication (Al). Male Wistar rats were randomly assigned into four experimental groups (n=6 each one): Sham (rats subjected to simulated surgery); Al+Sham; Partial Hepatectomy (animals subjected to 65% liver resection) and Al+Partial Hepatectomy. Our results show that both Partial Hepatectomy and Al treatment produce a decrease of plasma cholesterol level, which showed a negative association with Rigidity Index increase (r(s)=-0.6475, p<0.05). The increase of Rigidity Index observed in Partial Hepatectomy, Al+Sham and Al+Partial Hepatectomy could be related to the increase of the proportion of non-discocytic erythrocytes, particularly stomatocytes, which determines a diminution of the Morphological Index. In the Altreated groups, greater changes in Rigidity Index and Morphological Index were observed. The relative viscosity of blood at a standard haematocrit of 40% was increased in Partial Hepatectomy, Al+Sham and Al+Partial Hepatectomy as compared to Sham, due to erythrocyte rigidity. On the other hand, we observed that the increase of plasma fibrinogen concentration correlates with augmentation of plasma viscosity (r(s)=0.689, p=0.004) for all the experimental groups studied. The results indicate that both administration of Al and Partial Hepatectomy induce microcytic hypocromic anaemia in the rats reflected by a significant decrease of haematocrit, mean corpuscular volume and mean corpuscular haemoglobin concentration. From these results, we conclude that in partially hepatectomized, Al-overloaded rats the decrease in erythrocyte deformability may be an important factor leading to the installation of anaemia.

Urinary concentrating mechanism and Aquaporin-2 abundance in rats chronically treated with aluminum lactate.

The aim of this work was to study the effects of chronic administration of aluminum (Al) on the urinary concentrating and diluting mechanisms in the distal tubules and collecting ducts. Male Wistar rats were chronically treated with aluminum lactate for 12 weeks (0.575 mg Al/100g of body weight, i.p., three times per week). After 12 weeks, renal function of control and Al-treated rats was evaluated by clearance techniques. To study urinary concentrating mechanisms, renal function was also measured in control and Al-treated rats deprived of water, after the administration of desmopressin (vasopressin agonist) and after the infusion of hypertonic saline at increasing infusion rates. Sodium and water balance were impaired. We found decreased urinary concentrating ability in situations in which endogenous (thirst or infusion of hypertonic saline) or exogenous plasma antidiuretic hormone was increased. Solute-free water formation, measured during the infusion of hypotonic saline showed normal transport in the thick ascending limb. Aquaporin-2 (AQP2) expression was measured by Western blot to evaluate water permeability in collecting ducts. We found that Al produced downregulation of AQP2 in plasma membranes and intracellular vesicles, that could account for the impaired water handling. Administration of desmopressin increased AQP2 in plasma membranes, suggesting that Al did not impair trafficking of this protein, but could interfere with AQP2 synthesis.

Alterations of the renal function and oxidative stress in renal tissue from rats chronically treated with aluminium during the initial phase of hepatic regeneration.

Various indices of renal functions during the early stage of hepatic injury were studied in rats chronically treated with aluminum (Al) lactate. Tubular and hemodynamic parameters were analyzed four days after producing a 65% partial hepatectomy (PH). Water and sodium balances were also studied. Oxidative stress and the activity of Na-K-ATPase were determined in renal tissue. The rats were distributed in four groups: control, Al, PH, Al+PH. Al did not modify the hemodynamic renal functions and the PH-group reduced the glomerular filtrate rate (GFR). The Al + PH group presented a decrease in the renal blood flow and accentuated the GFR fall as compared with PH. The fractional excretion (FE) of water and sodium increased in the PH group. The rats chronically treated with Al and then submitted to the PH protocol developed a further increase in FE of water but a reduction in FE of sodium. Both PH and Al promoted an increase in the aldosterone. PH and Al induced a similar increase of the lipoperoxidation status with reduction of glutathione (GSH) and the activity of glutathione peroxidase (GSH-Px). The data indicated that Al is an inhibitor of catalase. The GSH and GSH-Px activity in the Al + PH group demonstrated a synergic effect of Al and PH. This work demonstrates that rats treated chronically with Al and submitted to another injury (such as hepatic damage) can aggravate renal functions, probably by increasing the oxidative state, at least in kidneys.

In vivo effect of aluminium upon the physical properties of the erythrocyte membrane.

Aluminium (Al (III)) is a metal with no biological function. Its organic accumulation can lead to toxic effects. To elucidate the in vivo effect of Al (III) upon the rheological properties of the erythrocyte membrane, male adult Wistar rats have been submitted to periodical injections of Al(OH)3 during three months. Significant decreases in haematocrit (34+/-0.37% versus 36+/-0.20%, p<0.0001) and blood haemoglobin concentration (10.7+/-0.15 g/dl versus 12.3+/-0.49 g/dl, p<0.005) have been found. Haemolysis curves shifted towards the left, indicating that erythrocytes became more resistant to hypotonic haemolysis. Significant increments in rigidity index (29.6+/-1.59 versus 9.2+/-0.40, p<0.0001), relative viscosity at native haematocrit (3.6+/-0.03 versus 3.5+/-0.03, p<0.04), and relative viscosity at standard haematocrit (4.5+/-0.06 versus 3.9+/-0.05, p<0.0001) have been observed. The decrease in the erythrocyte aggregate size (1.6+/-0.01 versus 1.7+/-0.01, p<0.002) and the aggregation rate (0.5+/-0.02 versus 0.6+/-0.03, p<0.002) indicated a significantly dropped aggregability process. In conclusion, Al (III) disorganised the erythrocyte membrane by altering its mechanical properties, suggesting a reduction of the middle life of circulating erythrocytes, which could play a major role in the anaemia of these animals.

Cresimiento y metabolismo del calcio en ratas sometidas a intoxicación crónica con hidróxido de aluminio / Growth and metabolism of calcio in rats chronically poisoned with aluminium hydroxide

Se estudiaron los efectos del aluminio sobre el crecimiento y desarrollo corporal, entre la 3 y 26 semanas de edad, en ratas intoxicadas crónicamente con hidróxido de aluminio (80 mg/kg peso ûi.p.- 3 veces por semana) y en ratas controles. El crecimiento fue evaluado de acuerdo a la teorfa de Parks de alimentación y crecimiento. El metabolismo del calcio al finalizar el perfodo de intoxicación, se estudió a través de un balance de calcio y la determinación de la velocidad de deposición y resorción ósea con ayuda de (45)Ca. Se examinó la función de la glándula paratiroides por un método indirecto. Se observó una disminución del peso corporal, sin afectarse la ingesta de alimento. El grupo tratado con aluminio se carcterizó por una reducción en la eficiencia inicial de conversión de alimento en biomasa. El aluminio no afectó la velocidad de crecimiento, ni el tiempo necesario para alcanzar la madurez. El balance de calcio en las ratas tratadas fue significativamente menor que en el grupo control. Esto fue acompañado de un aumento significativo del calcio excretado por heces, causado quizás por una menor absorción intestinal. Se observaron depósitos importantes de aluminio en la superficie del hueso trabecular y una disminución en la masa de calcio óseo en las ratas tratadas, no obstante no existen diferencias de esta última al ser expresada por 100 gr de peso corporal. La velocidad de deposición de Ca++ óseo disminuyó por efecto del aluminio, sin existir modificaciones en la velocidad de resorción ósea. La reducción del turnover óseo, reflejado por la disminución de Vo+/Vo-, fue acompañado por una menor velocidad en la recuperación de la calcemia, dato vinculado indirectamente a la respuesta de la glándula paratiroides a la hipocalcemia. En el modelo estudiado, la reducción del turnover óseo podrfa estar originado por los depósitos de aluminio en hueso, no obstante podrfan existir factores asociados como una disfunción en la secreción de PTH, o bien disminución de la afinidad en sus receptores a nivel óseo.

Cresimiento y metabolismo del calcio en ratas sometidas a intoxicación crónica con hidróxido de aluminio / Growth and metabolism of calcio in rats chronically poisoned with aluminium hydroxide

Se estudiaron los efectos del aluminio sobre el crecimiento y desarrollo corporal, entre la 3 y 26 semanas de edad, en ratas intoxicadas crónicamente con hidróxido de aluminio (80 mg/kg peso ¹i.p.- 3 veces por semana) y en ratas controles. El crecimiento fue evaluado de acuerdo a la teorfa de Parks de alimentación y crecimiento. El metabolismo del calcio al finalizar el perfodo de intoxicación, se estudió a través de un balance de calcio y la determinación de la velocidad de deposición y resorción ósea con ayuda de (45)Ca. Se examinó la función de la glándula paratiroides por un método indirecto. Se observó una disminución del peso corporal, sin afectarse la ingesta de alimento. El grupo tratado con aluminio se carcterizó por una reducción en la eficiencia inicial de conversión de alimento en biomasa. El aluminio no afectó la velocidad de crecimiento, ni el tiempo necesario para alcanzar la madurez. El balance de calcio en las ratas tratadas fue significativamente menor que en el grupo control. Esto fue acompañado de un aumento significativo del calcio excretado por heces, causado quizás por una menor absorción intestinal. Se observaron depósitos importantes de aluminio en la superficie del hueso trabecular y una disminución en la masa de calcio óseo en las ratas tratadas, no obstante no existen diferencias de esta última al ser expresada por 100 gr de peso corporal. La velocidad de deposición de Ca++ óseo disminuyó por efecto del aluminio, sin existir modificaciones en la velocidad de resorción ósea. La reducción del turnover óseo, reflejado por la disminución de Vo+/Vo-, fue acompañado por una menor velocidad en la recuperación de la calcemia, dato vinculado indirectamente a la respuesta de la glándula paratiroides a la hipocalcemia. En el modelo estudiado, la reducción del turnover óseo podrfa estar originado por los depósitos de aluminio en hueso, no obstante podrfan existir factores asociados como una disfunción en la secreción de PTH, o bien disminución de la afinidad en sus receptores a nivel óseo. (AU)