Influence Of Protein Malnutrition Research Articles

Influence of protein malnutrition on cutaneous wound healing in rats

ABSTRACT Objective Investigate histological changes related to inflammatory response and collagen expression during wound healing in rats with protein malnutrition. Methods Twenty male Wistar rats underwent cutaneous surgery and were divided into two experimental groups: Malnourished (8% casein diet); Nourished (17% casein diet). Animals were euthanized after 5th and 10th days, descriptive and quantitative analyses were performed on sections stained with hematoxylin-eosin and sirius red, respectively. Statistical analysis of data using nonparametric Fisher's exact test with p<0.05 was carried out. Results At five days, increased fibroblast proliferation (p<0.01) and collagen expression (p<0.05) was observed in N5 group. After ten days, N10 and MN10 animals showed higher amount of granulation tissue and edema/inflammatory infiltrate independent of nutritional status (p>0.05), only N10 group showed fibroblast proliferation (p<0.01) and increased collagen expression (p<0.01). Conclusion Protein malnutrition seems not to influence inflammatory phase of healing, whereas it negatively effects fibroblast proliferation and collagen synthesis.

The influence of protein malnutrition on the production of GM-CSF and M-CSF by macrophages

It is well established that protein malnutrition (PM) impairs immune defenses and increases susceptibility to infection. Macrophages are cells that play a central role in innate immunity, constituting one of the first barriers against infections. Macrophages produce several soluble factors, including cytokines and growth factors, important to the immune response. Among those growth factors, granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF). GM-CSF and M-CSF are important to monocyte and macrophage development and stimulation of the immune response process. Knowing the importance of GM-CSF and M-CSF, we sought to investigate the influence of PM on macrophage production of these growth factors. Two-month-old male BALB/c mice were subjected to PM with a low-protein diet (2%) and compared to a control diet (12%) mouse group. Nutritional status, hemogram and the number of peritoneal cells were evaluated. Additionally, peritoneal macrophages were cultured and the production of GM-CSF and M-CSF and mRNA expression were evaluated. To determine if PM altered macrophage production of GM-CSF and M-CSF, they were stimulated with TNF-α. The PM animals had anemia, leukopenia and a reduced number of peritoneal cells. The production of M-CSF was not different between groups; however, cells from PM animals, stimulated with or without TNF-α, presented reduced capability to produce GM-CSF. These data imply that PM interferes with the production of GM-CSF, and consequently would affect the production and maturation of hematopoietic cells and the immune response.

The influence of protein malnutrition on biological and immunomodulatory aspects of bone marrow mesenchymal stem cells

Tissues that require a great supply of nutrients and possess high metabolic demands, such as lympho-hemopoietics tissues, are the first to be affected by protein malnutrition (PM). Thus, PM directly affects hemopoiesis and the production and function of immune cells. Consequently, malnourished individuals are more susceptible to infections. Mesenchymal stem cells (MSCs) have immunomodulatory properties and are important in the formation of lympho-hemopoietic stroma. Since an adequate supply of nutrients is essential to sustain stroma formation, which is mainly constituted of MSCs and differentiated cells originated from them, this study investigated whether PM would influence some biological and immunomodulatory aspects of MSCs. Two-month-old Balb/c mice were divided into control and malnourished groups receiving normoproteic or hypoproteic diets, respectively (12% and 2% of protein) for 28 days. MSCs obtained from control (MSCct) and malnourished (MSCmaln) animals were characterized. In addition, the proliferation rate and cell cycle protein expression were determined, but no differences in these parameters were observed. In order to evaluate whether PM affects the immunomodulatory properties of MSCs, the expression of NFκB and STAT-3, and the production of IL-1α, IL-1β, IL-6, IL-10, TGF-β and TNF-α by MSCs were assessed. MSCmaln expressed lower levels of NF-κB and the production of IL-1β, IL-6 and TGF-β was significantly influenced by PM. Furthermore, MSCct and MSCmaln culture supernatants affected lymphocyte and macrophage proliferation. However, MSCmaln did not reduce the production of IFN-γ nor stimulate the production of IL-10 in lymphocytes in the same manner as observed in MSCct. Overall, this study implied that PM modifies immunosuppressive properties of MSCs.

The influence of protein malnutrition on the antifertility action of gossypol in the trypanosoma brucei-infected rat: Some ultrastructural observations from the testis

The testes of adult male Wistar rats that were variously protein malnourished, gossypol treated, and/or trypanosome infected ( Trypanosoma brucei) were evaluated ultrastructurally. The findings included several necrotic germ cells in the seminiferous epithelium and focal degeneration of Sertoli cells. Leydig cells showed a remarkable paucity of smooth endoplasmic reticulum, and aggregation of mitochondria. These observations were prevalent in those animals that were simultaneously protein-malnourished/gossypol treated/ trypanosome infected, and were either absent or markedly reduced in the other groups. These structural alterations are probably related to increased gossypol availability to the testis and/or represent the additive effects of gossypol and trypanosomes. Such tissue changes could compromise spermatogenesis in affected animals, and suggest that trypanosome infections may exacerbate testicular lesions in the gossypol-treated rat.

Influence of protein malnutrition on teratogenicity of acetylsalicylic acid in rats.

The effect of protein malnutrition (PM) on the embryotoxicity and teratogenicity of aspirin in rats has been studied. Protein malnourishment was produced from Days 7 to 21 of gestation by limiting the casein content of the diet to 5% in comparison to 20% for the normal animals. Six dose levels of aspirin (50-175 mg kg-1) were administered p.o. from Days 8 to 11 of pregnancy. Aspirin from 75 mg kg-1 d-1 induced growth retardation, embryolethality and teratogenicity, as shown by external, skeletal and visceral malformations. All these effects were potentiated by protein malnutrition.

The influence of protein malnutrition on T cell, natural killer cell, and lymphokine-activated killer cell function, and on biological responsiveness to high-dose interleukin-2

Protein malnutrition is prevalent in cancer patients, however the influence of protein-calorie malnutrition on anti-tumor immune effector mechanisms is unclear. In addition, the effect of malnutrition on host immunological and biological responsiveness to recombinant interleukin-2 (rIL-2) is unknown. In Swiss mice ( n = 100), we observed that T cell activation, T cell response to rIL-2, T suppressor cell generation, cytotoxic T lymphocyte development, and the cytolytic activity of LAK cells were not significantly impaired by two or three weeks of feeding with a 2.5% protein diet compared with mice fed an isocaloric diet in which protein calories constituted 24% of the total. In CBA/J mice ( n = 100), we observed a significant ( P < 0.05) impairment of poly(I:C)-inducible natural killer cell function in mice ingesting the 2.5% diet. In both A/J ( n = 40) and Swiss mice ( n = 40), cytotoxic responses after 3 days treatment with rIL-2 (5 × 10 6 U/kg body wt. three times daily) were comparable in both dietary groups. These studies demonstrate that protein depletion is associated with impaired poly(I:C)-induced natural killer cell function in CBA/J mice. However, T cell function and biological responsiveness to high-dose rIL-2 were not significantly impaired.

Effect of protein malnutrition on the metabolism of uteral collagen in the rat

The effect of protein malnutrition on the metabolism of collagen was studied in young female albino rats after a single injection of 3H-proline by determining the specific as well as total activities of 3H-hydroxyproline in the skin collagen fractions and in the urine. a) Compared to controls, the total activity of 3H-hydroxyproline in the soluble collagen and in the urine was significantly lower in the deficient group at 12 hrs. after the administration of 3H-proline. b) The urinary excretion of hydroxyproline and the total activity of urinary 3H-hydroxyproline measured after four weeks of labelled proline injection were also considerably decreased in the protein-deficient animals. c) When the total radioactivities of both soluble and insoluble collagen are expressed as a percentage of the sum of both, the recorded activity was more in soluble and less in insoluble collagen at 12 and 120 hrs. after the administration of 3H-proline, due to the influence of protein malnutrition. The results of the present investigation therefore clearly indicate that the synthesis of collagen is decreased and accompanied by a retardation in the maturation of soluble to insoluble collagen in the protein-deficient animals compared to controls. In addition, protein deficiency is accompanied by decreased rates of catabolism of both soluble and insoluble collagen.

The influence of protein malnutrition on ileal permeability to macromolecules in the rat.

Ileal absorption of intact protein was assessed in groups of control and protein-deficient rats during a 5-month period of dietary protein restriction. At monthly intervals following diet initiation, 3 animals from both the control and deficient groups were administered horseradish peroxidase via ligated ileal loops either 15, 45 or 90 minutes before loop excision and processing for light and electron microscopy. Morphological evaluations revealed no change in pinocytotic activity during the 5 months of progressive protein malnutrition. After 3 months, however, partial deterioration of mucosal structure was observed with apparent separation of apical intercellular junctions and movement of peroxidase molecules directly between cells. These observations in the ileum are compared to previous findings in the jejunum. It is suggested that ileal and jejunal absorptive cells respond uniquely to protein deprivation but that eventual junctional deterioration occurs in both regions with potential detrimental consequences for the host.