ACTIVATION OF THE NEUTROPHIL AND LOSS OF PLASMA GLUTATHIONE DURING MG-DEFICIENCY - MODULATION BY NITRIC-OXIDE SYNTHASE INHIBITION

Sprague-Dawley rats (200 g) were fed either a Mg-deficient or Mg-suffi cient diet for 3 weeks. An enriched neutrophil fraction (>85%) was iso lated from the blood by sodium metrizoate/dextran gradient centrifugat ion. Using the superoxide dismutase (SOD)-inhibitable cytochrome c red uction assay, the basal activity of neutrophils isolated from the Mg-d eficient rats were found elevated 5 fold after two weeks, and up to si milar to 7 fold after three weeks on the diet. Upon challenge by phorb ol myristate acetate (PMA), unlike the Mg-sufficient cells, the Mg-def icient cells exhibited no significant activation. Treatment of the Mg- deficient rats with the nitric oxide (NO)-synthase inhibitor, N-G-nitr o-L-arginine methyl ester (L-NAME) in the drinking water, significantl y attenuated the basal superoxide producing activity of the neutrophil s and partially restored its response to PMA challenge. In association with the neutrophil activation. Mg-deficiency resulted in 70% decreas e in plasma glutathione and 220% increase in Fe-promoted, thiobarbitur ic acid reactive substance (TEARS) levels; both changes were significa ntly attenuated by L-NAME treatment. The results suggest that neutroph ils 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 lowere d by NO-synthase inhibition suggesting that NO overproduction during M g-deficiency participates in the neutrophil activation process.