Activation of the neutrophil and loss of plasma glutathione during Mg-deficiency – modulation by nitric oxide synthase inhibition |
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Authors: | Mak I Tong Dickens Benjamin F Komarov Andrei M Wagner Tammy L Phillips Terry M Weglicki William B |
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Institution: | (1) Department of Medicine, Division of Experimental Medicine, The George Washington University Medical Center, Washington, DC, 20037, USA;(2) Department of Physiology, Division of Experimental Medicine, The George Washington University Medical Center, Washington, DC, 20037, USA |
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Abstract: | Sprague-Dawley rats (200 g) were fed either a Mg-deficient or Mg-sufficient diet for 3 weeks. An enriched neutrophil fraction (>85%) was isolated from the blood by sodium metrizoate/dextran gradient centrifugation. Using the superoxide dismutase (SOD)-inhibitable cytochrome c reduction assay, the basal activity of neutrophils isolated from the Mg-deficient rats were found elevated 5 fold after two weeks, and up to 7 fold after three weeks on the diet. Upon challenge by phorbol myristate acetate (PMA), unlike the Mg-sufficient cells, the Mg-deficient cells exhibited no significant activation. Treatment of the Mg-deficient rats with the nitric oxide (NO)-synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) in the drinking water, significantly attenuated the basal superoxide producing activity of the neutrophils and partially restored its response to PMA challenge. In association with the neutrophil activation. Mg-deficiency resulted in 70% decrease in plasma glutathione and 220% increase in Fe-promoted, thiobarbituric acid reactive substance (TBARS) levels; both changes were significantly attenuated by L-NAME treatment. The results suggest that neutrophils from Mg-deficient rats are activated endogenously to generate oxy-radicals which might directly mediate the in vivo peroxidative indices during Mg-deficiency. Furthermore, the neutrophil activity was lowered by NO-synthase inhibition suggesting that NO overproduction during Mg-deficiency participates in the neutrophil activation process. |
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Keywords: | Mg-deficiency rats nitric oxide synthesis neutrophil activation oxidative stress plasma glutathione |
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