Zinc Deficiency Affects DNA Damage, Oxidative Stress, Antioxidant Defenses, and DNA Repair in Rats

Department of Nutrition and Exercise Science and 5Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
Journal of Nutrition (Impact Factor: 4.23). 08/2009; 139(9):1626-31. DOI: 10.3945/jn.109.106369
Source: PubMed

ABSTRACT Approximately 12% of Americans do not consume the Estimated Average Requirement for zinc and could be at risk for marginal zinc deficiency. Zinc is an essential component of numerous proteins involved in the defense against oxidative stress and DNA damage repair. Studies in vitro have shown that zinc depletion causes DNA damage. We hypothesized that zinc deficiency in vivo causes DNA damage through increases in oxidative stress and impairments in DNA repair. Sprague-Dawley rats were fed zinc-adequate (ZA; 30 mg Zn/kg) or severely zinc-deficient (ZD; <1 mg Zn/kg) diets or were pair-fed zinc-adequate diet to match the mean feed intake of ZD rats for 3 wk. After zinc depletion, rats were repleted with a ZA diet for 10 d. In addition, zinc-adequate (MZA 30 mg Zn/kg) or marginally zinc-deficient (MZD; 6 mg Zn/kg) diets were given to different groups of rats for 6 wk. Severe zinc depletion caused more DNA damage in peripheral blood cells than in the ZA group and this was normalized by zinc repletion. We also detected impairments in DNA repair, such as compromised p53 DNA binding and differential activation of the base excision repair proteins 8-oxoguanine glycosylase and poly ADP ribose polymerase. Importantly, MZD rats also had more DNA damage and higher plasma F(2)-isoprostane concentrations than MZA rats and had impairments in DNA repair functions. However, plasma antioxidant concentrations and erythrocyte superoxide dismutase activity were not affected by zinc depletion. These results suggest interactions among zinc deficiency, DNA integrity, oxidative stress, and DNA repair and suggested a role for zinc in maintaining DNA integrity.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Aspergillus fumigatus is able to invade and grow in the lungs of immunosuppressed individuals and causes invasive pulmonary aspergillosis. The concentration of free zinc in living tissues is much lower than that required for optimal fungal growth in vitro because most of it is tightly bound to proteins. To obtain efficiently zinc from a living host A. fumigatus uses the zinc transporters ZrfA, ZrfB, and ZrfC. The ZafA transcriptional regulator induces the expression of all these transporters and is essential for virulence. Thus, ZafA could be targeted therapeutically to inhibit fungal growth. The ZrfC transporter plays the major role in zinc acquisition from the host whereas ZrfA and ZrfB rather have a supplementary role to that of ZrfC. In addition, only ZrfC enables A. fumigatus to overcome the inhibitory effect of calprotectin, which is an antimicrobial Zn/Mn-chelating protein synthesized and released by neutrophils within the fungal abscesses of immunosuppressed non-leucopenic animals. Hence, fungal survival in these animals would be undermined upon blocking therapeutically the function of ZrfC. Therefore, both ZafA and ZrfC have emerged as promising targets for the discovery of new antifungals to treat Aspergillus infections.
    Frontiers in Microbiology 02/2015; 6:160. DOI:10.3389/fmicb.2015.00160 · 3.94 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND Developmental zinc (Zn) deficiency increases the incidence of heart anomalies in rat fetuses, in regions and structures derived from the outflow tract. Given that the development of the outflow tract requires the presence of cardiac neural crest cells (cNCC), we speculated that Zn deficiency selectively kills cNCC and could lead to heart malformations.METHODS Cardiac NCC were isolated from E10.5 rat embryos and cultured in control media (CTRL), media containing 3 μM of the cell permeable metal chelator N, N, N′, N′-tetrakis (2-pyridylmethyl) ethylene diamine (TPEN), or in TPEN-treated media supplemented with 3 μM Zn (TPEN + Zn). Cardiac NCC were collected after 6, 8, and 24 h of treatment to assess cell viability, proliferation, and apoptosis.RESULTSThe addition of TPEN to the culture media reduced free intracellular Zn pools and cell viability as assessed by low ATP production, compared to cells grown in control or Zn-supplemented media. There was an accumulation of reactive oxygen species, a release of mitochondrial cytochrome c into the cytoplasm, and an increased cellular expression of active caspase-3 in TPEN-treated cNCC compared to cNCC cultured in CTRL or TPEN + Zn media.CONCLUSION Zn deficiency can result in oxidative stress in cNCC, and subsequent decreases in their population and metabolic activity. These data support the concept that Zn deficiency associated developmental heart defects may arise in part as a consequence of altered cNCC metabolism
    Birth Defects Research Part B Developmental and Reproductive Toxicology 02/2015; DOI:10.1002/bdrb.21135 · 1.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: An increased intake of Zinc (Zn) may reduce the risk of degenerative diseases but may prove to be toxic if taken in excess. This study aimed to investigate whether Zinc carnosine supplement can improve Zn status, genome stability events and Zn transporter gene expression in an elderly (65-85y) South Australian cohort with low plasma Zn levels. A 12 week placebo-controlled intervention trial was performed with 84 volunteers completing the study, (Placebo, n = 42) and (Zn group, n = 42). Plasma Zn was significantly increased (p<0.05) by 5.69% in the Zn supplemented group after 12 weeks. A significant (p<0.05) decrease in the micronucleus frequency (-24.18%) was observed for the Zn supplemented cohort relative to baseline compared to the placebo group. Reductions of -7.09% for tail moment and -8.76% for tail intensity were observed for the Zn group (relative to baseline) (p<0.05). Telomere base damage was found to be also significantly decreased in the Zn group (p<0.05). Both MT1A and ZIP1 expression showed a significant increase in the Zn supplemented group (p<0.05). Zn supplementation may have a beneficial effect in an elderly population with low Zn levels by improving Zn status, antioxidant profile and lowering DNA damage. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Molecular Nutrition & Food Research 03/2015; DOI:10.1002/mnfr.201400784 · 4.91 Impact Factor


Available from