Clinical, Immunological, Anti-inflammatory and Antioxidant Roles of Zinc
Prasad AS.
Exp Gerontol May 2008 ; 43(5):370-7.
The essentiality of zinc for humans was recognized only 40 years ago. Zinc deficiency was suspected to occur in Iranian patients with growth retardation, hypogonadism in males, hepato-splenomegaly, rough and dry skin, geophagia and severe iron deficiency anemia. Later we documented zinc deficiency in similar patients in Egypt. The diet of these patients consisted of mainly cereal proteins which contained high phytate and this led to decreased availability of iron and zinc. These patients had severe immune dysfunctions, inasmuch as they died of intercurrent infections by the time they were 25 years of age. In our studies in experimental human model of zinc deficiency, we documented decreased serum testosterone level, oligospermia, severe immune dysfunctions mainly affecting T helper cells, decreased serum thymulin activity hyperammonemia, neuro-sensory disorders and decreased lean body mass. The basic mechanisms of zinc action on immune cells have been reviewed in this paper. Our studies showed that the activation of many zinc dependent enzymes and transcription factors were affected adversely due to zinc deficiency. The gene expression and production of Th1 cytokines were affected adversely due to zinc deficiency. Zinc is also an antioxidant and has anti-inflammatory actions. We have reported decreased plasma zinc, increased plasma oxidative stress markers and increased generation of inflammatory cytokines in the elderly subjects which were corrected by zinc supplementation. In cell culture studies, we have observed that zinc induces A20 which inhibits NF-kappaB activation resulting indecreased generation of inflammatory cytokines.
Effect of Zinc on Cellular Poly(ADP-ribosyl)ation Capacity
Kunzmann A, et al.
Exp Gerontol, May 2008 ; 43(5) :409-14.
Poly(ADP-ribosyl)ation is a posttranslational protein modification, which is catalyzed by poly(ADP-ribose) polymerase-1 (PARP-1) and plays a role in DNA repair and maintenance of genomic stability. A decrease in cellular poly(ADP-ribosyl)ation has been implicated in the aging process. As PARP-1 is a zinc finger protein its decreased function might be related to age related zinc deficiency. To test this hypothesis we assessed cellular poly(ADP-ribosyl)ation capacity in 29 donors from Greece, Italy and Poland as function of age and nutritional zinc status. Our results reveal a positive correlation between cellular poly(ADPribosyl) ation capacity and zinc status in human peripheral blood mononuclear cells (PBMC) (p<0.05). We could also confirm a decrease of PARP-1 activity with donor age, highlighting the role of poly(ADP-ribosyl)ation in the aging process. The results demonstrate that zinc supplementation in elderly people can increase the cellular poly(ADP ribosyl)ation capacity of their PBMC. We speculate that this may help maintain integrity and stability of the genome more efficiently and thus contribute to an extension of healthspan.
Zinc Supplementation in the Elderly Subjects: Effect on Oxidized Protein Degradation and
Repair Systems in Peripheral Blood Lymphocytes
Cabreiro F, et al.
Exp Gerontol ; May 2008 ; 43(5) :483-7.
Aging has been associated with zinc deficiency, leading to chronic inflammation and subsequent oxidative stress, especially in the immune system. The increased oxidative stress provokes the accumulation of oxidized proteins, raising the problem of the efficacy of intracellular protein maintenance systems responsible for the elimination of oxidatively modified proteins. Our objective was to analyze the effect of zinc supplementation in the elderly on protein maintenance in peripheral blood
lymphocytes. The status of the proteasome, which is in charge of oxidized protein degradation and the repair enzymes peptide methionine sulfoxide reductases, which can reverse methionine oxidation in proteins, were analyzed on peripheral blood lymphocytes collected from 20 elderly subjects (age range between 59 and 85 years old) before and after zinc supplementation (10mg of zinc per day for 48+/-2 days). A decrease of oxidized protein content in zinc supplemented subjects was observed and was associated with an increase of expression levels and/or activities of proteasome and methionine sulfoxide reductases. Our results indicate that zinc treatment could enhance the antioxidative defences of peripheral blood lymphocytes by increasing the activities of protein maintenance systems responsible for the elimination of oxidatively modified proteins.
Zinc Supplementation Boosts the Stress Response in the Elderly: Hsp70 Status is Linked to
Zinc Availability in Peripheral Lymphocytes
Putics A, et al.
Exp Gerontol ; May 2008 ; 43(5) :452-61.
Chaperones and zinc are indispensable for proper immune function. All the zinc status, the immune function and the stress response decline during aging. Here we studied the effect of nutritional zinc and zinc homeostasis on the stress response in healthy old subjects recruited during the ZincAge European Union project that either underwent or not a 48day zinc supplementation. Inducible Hsp70 levels were determined at basal conditions as well as after heat shock in the CD3+ and CD3- subset of lymphocytes by a two-color FACS analysis. Short term zinc supplementation resulted in a marked increase in both basal as well as stress-induced Hsp70 levels in lymphocytes from healthy elderly donors with a higher impact on CD3+ cells. Heat inducibility showed a strong correlation with basal Hsp70 level, and both basal as well as stress-induced Hsp70 highly correlated with intracellular zinc availability. In conclusion, short term oral supplementation with zinc safely and efficiently induces the stress response in lymphocytes of old donors. The stress response may be a candidate pathway connecting zinc deficiency with aging and immunosenescence. Thus, proper dietary zinc intake may emerge as a chaperone inducer and an anti-aging mechanism in the immune system.
Effect of Zinc Supplementation on Respiratory Tract Infections in Children with Cystic
Fibrosis
Abdulhamid I, et al.
Pediatr Pulmonol ; March 2008 ; 43(3) :281-7.
Zinc (Zn) has significant anti-oxidant and anti-inflammatory activity. Zn deficiency can occur in subsets of patients with cystic fibrosis (CF) especially those with malabsorption and impaired growth. Although supplemental Zn has significantly reduced infections in various disorders, its efficacy has not been thoroughly investigated in CF. We performed a double blind placebo controlled pilot study to investigate the effect of daily 30 mg elemental Zn for 1 year on the rate of respiratory tract infections (RTls), use of antibiotics and plasma cytokines in 26 children with CF (ages 7-18 years). Plasma Zn, Cu, inflammatory cytokines and ex vivo generation of IL-2 were measured at baseline and at the end of the study. The number of days of oral antibiotics was lower in Zn treated patients compared to placebo (P = 0.05). However, compared to placebo, the effect of Zn was greater in patients who exhibited low plasma Zn at baseline (P = 0.02) than those who had plasma Zn levels identical to normal subjects (P = 0.55). Zn supplementation was marginally effective in reducing percentage increase in plasma IL-6 and IL-8 while increasing the percentage change in ex vivo generation of IL2 in isolated mononuclear cell. In conclusion, oral intake of 30 mg/day of Zn reduced the number of days of oral antibiotics used to treat RTls in children with CF. A higher daily Zn dosemay be needed to decrease RTls and modify immune responses.
The Influence of Selenium on Immune Responses.
Hoffmann PR, Berry MJ.
Mol Nutr Food Res ; Apr 2 2008 ; [Epub ahead of print].
Poly(ADP-ribosyl)ation is a posttranslational protein modification, which is catalyzed by poly(ADP-ribose) polymerase-1 (PARP-1) and plays a role in DNA repair and maintenance of genomic stability. A decrease in cellular poly(ADP-ribosyl)ation has been implicated in the aging process. As PARP-1 is a zinc finger protein its decreased function might be related to age related zinc deficiency. To test this hypothesis we assessed cellular poly(ADP-ribosyl)ation capacity in 29 donors from Greece, Italy and Poland as function of age and nutritional zinc status. Our results reveal a positive correlation between cellular poly(ADPribosyl) ation capacity and zinc status in human peripheral blood mononuclear cells (PBMC) (p<0.05). We could also confirm a decrease of PARP-1 activity with donor age, highlighting the role of poly(ADP-ribosyl)ation in the aging process. The results demonstrate that zinc supplementation in elderly people can increase the cellular poly(ADP ribosyl)ation capacity of their PBMC. We speculate that this may help maintain integrity and stability of the genome more efficiently and thus contribute to an extension of healthspan.
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