Stress protein expression cDNA array study supports activation of neutrophils during acute magnesium deficiency in rats.

Recent studies underline the importance of the immunoinflammatory processes in the pathology of acute magnesium (Mg)-deficiency. The aim of this study was to assess the effect of acute experimental Mg-deficiency in the rat on neutrophil activity. Weaning male Wistar rats were fed either a Mg-deficient or a control diet for 8 days. In this experiment, we measured neutrophil respiratory burst by chemiluminescence; then, to examine the molecular events associated with acute Mg-deficiency, we applied cDNA array technology to define the transcription response in neutrophils of Mg-deficient rats in comparison with controls. In Mg-deficient rats, the characteristic inflammatory response was accompanied by a marked increase in the number of neutrophils. Moreover, as shown by chemiluminescence studies, basal neutrophil activity from Mg-deficient rats was significantly elevated when compared to neutrophils from control rats. Moreover, the chemiluminescence of neutrophils from Mg-deficient rats was significantly higher than that of control rats following phorbol myristate acetate or opsonized zymosan activation. Using cDNA array which includes 207 known rat genes of stress proteins, 102 genes were found to be expressed in neutrophils. Among expressed genes, 78 per cent of genes were found to be expressed more than twofold in neutrophils from Mg-deficient rats compared to control rats. Acute Mg-deficiency was characterized by an induction of genes encoding for proteins involved in apoptosis, heat shock proteins, protein belonging to the cytoskeleton, proteins implicated as stress response regulators and effectors and enzyme implicated in thromboxane synthesis. Then, this experimental strategy allowed to identify a series of genes implicated in the immunoinflammatory process of Mg-deficiency.

Amino acid nutrition and immune function in tumour-bearing rats: a comparison of glutamine-, arginine- and ornithine 2-oxoglutarate-supplemented diets.

Dietary supplementation with glutamine (Gln), arginine (Arg) or ornithine 2-oxoglutarate (alpha-ketoglutarate; OKG) has attracted recent attention for the potential to improve anti-cancer immune function. However, since these compounds have not been compared systematically in an internally controlled study, their relative efficacy is difficult to estimate. Buffalo rats were fed on nutritionally complete semi-purified diets supplemented with Gln, Arg or OKG for 14 days after implantation of the Morris hepatoma 7777 (n>/=7 per diet). The control diet was made isonitrogenous and isoenergetic by addition of a mixture of non-essential amino acids. After 14 days, peritoneal macrophages and splenocytes were isolated to determine cell phenotypes, macrophage cytostatic activity and natural killer (NK) cell cytotoxicity, as well as nitric oxide (NO) and cytokine production. Diet had no effect on tumour weight (1.6+/-0.2 g; n=59). However, rats fed OKG had increased macrophage cytostatic activity and NK cell cytotoxicity (P<0.05). Although enhanced killing ability by NK cells was associated with higher splenocyte NO production (P<0.04), increased cytotoxicity was not inhibited by a specific inhibitor of inducible NO synthase. The proportion of interleukin-2-receptor-positive T cells after stimulation increased in rats fed OKG (P<0.05); however, cytokine production was not affected by diet. None of OKG, Gln or Arg altered tumour growth compared with a control mixture of non-essential amino acids. These results suggest no net advantage for anti-cancer immunity, but do not preclude benefits in immune responses to disease recurrence or metastasis, therapy or secondary infection.