Oxidative Stress and Genomic Damage Induced In Vitro in Human Peripheral Blood by Two Preventive Treatments of Iron Deficiency Anemia

  • Rocío Celeste GambaroEmail author
  • Analía Seoane
  • Gisel Padula


Iron deficiency is the most prevalent nutritional deficiency and the main cause of anemia worldwide. Since children aged 6–24 months are among the most vulnerable groups at risk, daily supplementation with ferrous sulfate is recommended by the Argentine Society of Pediatrics as preventive treatment of anemia. However, a single weekly dose would have fewer adverse side effects and has been therefore proposed as an alternative treatment. Ferrous sulfate is known by its pro-oxidative properties, which may lead to increased oxidative stress as well as lipid, protein, and DNA damage. We analyzed the effect of daily and weekly preventive treatment of iron deficiency anemia (IDA) on cell viability, oxidative stress, chromosome, and cytomolecular damage in peripheral blood cultured in vitro. The study protocol included the following: untreated negative control; bleomycin, hydrogen peroxide, or ethanol-treated positive control; daily 0.14 mg ferrous sulfate–supplemented group; and weekly 0.55 mg ferrous sulfate–supplemented group. We assessed cell viability (methyl-thiazolyl-tetrazolium and neutral red assays), lipid peroxidation (thiobarbituric acid reactive substances assay), antioxidant response (superoxide dismutase and catalase enzyme analysis), chromosome damage (cytokinesis-blocked micronucleus cytome assay), and cytomolecular damage (comet assay). Lipid peroxidation, antioxidant response, and chromosome and cytomolecular damage decreased after weekly ferrous sulfate supplementation (p < 0.05), suggesting less oxygen free radical production and decreased oxidative stress and genomic damage. Such a decrease in oxidative stress and genomic damage in vitro positions weekly supplementation as a better alternative for IDA treatment. Further studies in vivo would be necessary to corroborate whether weekly supplementation could improve IDA preventive treatment compliance in children.


Ferrous sulfate Anemia Iron deficiency Oxidative stress DNA damage Pediatrics 



The authors thank Adriana Di Maggio for careful manuscript translation and editing and César E. Bianchi for technical assistance.


This study was supported with funds provided by the National Scientific and Technical Research Council of Argentina (Grant No. 0657) and La Plata National University (Grants V246 and V249).

Compliance with Ethical Standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Declarations of Interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.IGEVET – Instituto de Genética Veterinaria “Ing. Fernando N. Dulout” (UNLP-CONICET LA PLATA), Facultad de Ciencias Veterinarias UNLPLa PlataArgentina
  2. 2.Facultad de Ciencias Naturales y MuseoUniversidad Nacional de La PlataLa PlataArgentina

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