Effect of starvation and refeeding on biochemical and immunological status of Balb/c mice: an experimental model of malnutrition.
ABSTRACT Although new methods for the induction of malnutrition disorders in laboratory animals have been developed, the bulk of the models described in the literature are essentially based on dietary restriction/starvation principle. In this context, little data are available about the metabolic and the immune system parameters of Balb/c mice under starvation/refeeding.
This study examined the effects of starvation and refeeding on the biochemical and immunological status of undernourished Balb/c mice.
Female Balb/c mice, weighing 20 g, were starved for 3 days and then refed with commercial pelleted diet for 8 days. The variables considered were as follows: body weight; serum protein and amino acid concentrations; liver protein content, and cholinesterase and arginase activities; jejunal protein and DNA contents as well as oligosaccharidase levels; hematological parameters (bone marrow and peripheral blood cellularity); peritoneal macrophage activation; and humoral and cell-mediated immune functions.
Profound alterations in both biochemical and immunological conditions appeared after the starvation period. Refeeding resulted in the normalization of serum albumin levels, the intestinal DNA content and the gut-mucosal associated enzymatic activities, the blood lymphocyte counts, and the number of peritoneal macrophages. The markers of liver metabolic function (cholinesterase and arginase activities), and those of bone marrow hemopoiesis and the adaptive immune response (T-dependent antibody titres and delayed-type hypersensitivity response) remained altered after refeeding compared with control mice.
These findings suggest that fasted mice can be used as an animal model of acute starvation that might prove useful in evaluating the effectiveness of nutritional and immunopharmacological interventions.
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ABSTRACT: Protein calorie malnutrition is known to induce various macrophage dysfunctions, such as the impairment of their phagocytic function, proliferative capacity, and bactericidal activity. However, little is known about the behavior of Kupffer cells under protein calorie malnutrition in vivo. To investigate the behavior of Kupffer cells under protein calorie malnutrition, we fed mice on a low protein (protein-derived) diet for 4 weeks and examined the number, cytologic changes, and proliferative capacity of their Kupffer cells. To detect macrophage precursor cells, colony-forming assays were performed in the bone marrow, spleen, and liver of the mice. To investigate the relationship of Kupffer cells to CSF, the serum levels of IL-6 and granulocyte-macrophage colony-stimulating factor were measured by ELISA, and the expression of macrophage colony-stimulating factor (M-CSF) mRNA in the liver was determined by Northern blot analysis. The recovery processes of Kupffer cells in the protein-deprived mice after normal protein feeding or daily recombinant human macrophage colony-stimulating factor administration were also investigated. In the protein-deprived mice, Kupffer cells decreased in number to two-thirds that of the normally fed (nondeprived) mice, showed the cytologic and ultrastructural features of maturation failure, and had reduced proliferative capacity. After normal protein feeding or recombinant human macrophage colony-stimulating factor administration, the number, morphology, and proliferative capacity of the Kupffer cells in the liver returned to normal, and they matured as in the nondeprived mice. In the protein-deprived mice, the serum levels of IL-6 and granulocyte-macrophage colony-stimulating factor increased, and the expression of M-CSF mRNA in the liver was reduced. In the bone marrow, the granulocyte-macrophage colony-forming cells and macrophage colony-forming cells were increased, and the influx of monocytes into the liver was temporarily enhanced; however, the number of monocytes in the peripheral blood was decreased. These results suggest that the reduced production of M-CSF in the liver of protein-deprived mice results in numerical reduction, maturation failure, and decreased proliferative capacity of Kupffer cells.Laboratory Investigation 07/1995; 72(6):696-706. · 3.96 Impact Factor
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ABSTRACT: The present study was carried out to compare the effects of four isoenergetic and isonitrogenous diets on the N utilization, total serum protein concentration and serum amino acid profile in starved rats at weaning. These diets differed only in the molecular form of two milk proteins (whey protein and casein), which were either native or partly hydrolysed. Male Wistar rats at weaning were fasted for 3 d and then refed with one of the four diets for 48 h. No differences were observed in the body weight gain, protein digestibility and total serum protein concentration between groups after the refeeding period and all the N balances were positive. N retention was higher in the two groups of rats given the protein-hydrolysate-based diets compared with those given the intact-protein-based diets. This was associated with a lower urinary N excretion in rats, given the whey-protein-hydrolysate and the casein-hydrolysate diets. Despite this fact, the serum amino acid pattern of rats given the hydrolysed protein diet was very similar to that of those given the corresponding native protein diet. In conclusion, we have proved that enzymic hydrolysates from milk proteins have equivalent effects to native proteins in recovery after starvation in rats at weaning, on N absorption, total serum protein concentration and serum amino acid profile, and even give a higher N retention. We did not observe any harmful effect in using protein hydrolysates instead of native proteins.British Journal Of Nutrition 02/1995; 73(1):65-71. · 3.30 Impact Factor
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ABSTRACT: Important regulatory factors of intrahepatic protein synthesis and proteolysis are amino acids, glucagon, insulin, and cell volume. We have investigated the changes in these factors with development and after an overnight fast and evaluated their contribution to changes in the hepatic nitrogen balance in vivo. In the fed state, glucagon levels were highest in suckling animals and gradually declined in older rats, whereas the concentration of insulin increased during development. The amino acid concentrations in liver and plasma declined during the suckling period to levels that in vitro are highly permissive for induction of autophagic proteolysis. In all age groups investigated, fasting was associated with a drop in hepatic protein content, together with a marked decrease in hepatocellular volume and insulin concentrations. On the other hand, glucagon concentrations and the concentration of many amino acids in plasma and liver responded to fasting with a pronounced decrease in perinatal and suckling animals, but this response had become blunted at weaning and had disappeared in adult animals. These findings suggest that insulin and/or hepatocellular volume are more likely candidates as short-term physiologic regulators of the hepatic nitrogen balance than are glucagon or amino acids. In glucose-supplemented fetuses, high levels of insulin could not compensate for a decreased hepatocellular volume in averting a catabolic state, suggesting that cell volume is the more important factor. Although our study cannot discriminate between the effects of fasting on protein synthesis and degradation, our findings show unequivocally that, for a rapid growth of the liver, suckling animals have to be fed around-the-clock.Pediatric Research 01/1996; 38(6):1018-25. · 2.67 Impact Factor