title: Zinc supplementation decreases oxidative stress, incidence of infection, and generation of inflammatory cytokines in sickle cell disease patients.
abstract: Zinc deficiency is common in adult sickle-cell disease (SCD) patients. We previously demonstrated that zinc supplementation to adult SCD patients decreased the incidences of infections and hospital admissions. We hypothesize that zinc supplementation improves T-helper cell function and decreases vascular endothelial cell activation, oxidative stress, and nuclear factor-kappa B (NF-kappaB)-DNA binding in mononuclear cells (MNCs) in SCD patients. To test this hypothesis, 36 SCD patients were recruited and randomly divided into 2 groups. One group (n = 18) received 25-mg zinc orally thrice a day for 3 months. The other group (n = 18) received placebo. The results indicate that the zinc-supplemented group had decreased incidence of infections compared with the placebo group. After zinc supplementation, red blood cell, hemoglobin (Hb), hematocrit, (Hct), plasma zinc, and antioxidant power increased; plasma nitrite and nitrate (NOx), lipid peroxidation products, DNA oxidation products, and soluble vascular cell adhesion molecule-1 decreased in the zinc-supplemented group, compared with the placebo group. Zinc-supplemented patients exhibited significant decreases in lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-alpha) and IL-1beta mRNAs, and TNF-induced nuclear factor of kappaB-DNA binding in MNCs, compared with the placebo group. Ex vivo addition of zinc to MNCs isolated from the placebo subjects decreased TNF-alpha and IL-1beta mRNAs. Zinc supplementation also increased relative levels of IL-2 and IL-2Ralpha mRNAs in phytohemagglutinin-p-stimulated MNCs. These results suggest that zinc supplementation may be beneficial to SCD patients.
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. bbao@med.wayne.edu
authors.forename: Bin
authors.initials: B
authors.lastname: Bao
authors.forename: Ananda S
authors.initials: AS
authors.lastname: Prasad
authors.forename: Frances W J
authors.initials: FW
authors.lastname: Beck
authors.forename: Diane
authors.initials: D
authors.lastname: Snell
authors.forename: Anupam
authors.initials: A
authors.lastname: Suneja
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.forename: Nimisha
authors.initials: N
authors.lastname: Doshi
authors.forename: James T
authors.initials: JT
authors.lastname: Fitzgerald
authors.forename: Paul
authors.initials: P
authors.lastname: Swerdlow
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D004247:DNA / Q000378:metabolism; D019587:Dietary Supplements; D005786:Gene Expression Regulation / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D015994:Incidence; D007239:Infections / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008824:Michigan / Q000453:epidemiology; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015032:Zinc / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D015032:Zinc