PUBLICATION

α-Lipoic Acid Reduces Iron-induced Toxicity and Oxidative Stress in a Model of Iron Overload

Authors
Camiolo, G., Tibullo, D., Giallongo, C., Romano, A., Parrinello, N.L., Musumeci, G., Di Rosa, M., Vicario, N., Brundo, M.V., Amenta, F., Ferrante, M., Copat, C., Avola, R., Li Volti, G., Salvaggio, A., Di Raimondo, F., Palumbo, G.A.
ID
ZDB-PUB-190203-10
Date
2019
Source
International Journal of Molecular Sciences   20(3): (Journal)
Registered Authors
Keywords
alpha lipoic acid, iron, oxidative stress, toxicity, zebrafish
MeSH Terms
  • Animals
  • Autophagy/drug effects
  • Cell Line
  • Disease Models, Animal
  • Ferric Compounds/adverse effects*
  • Glutathione/metabolism
  • Heme Oxygenase-1/genetics
  • Humans
  • Iron Chelating Agents/administration & dosage*
  • Iron Chelating Agents/pharmacology
  • Iron Overload/chemically induced
  • Iron Overload/drug therapy*
  • Iron Overload/genetics
  • Iron Overload/metabolism
  • Oxidative Stress/drug effects
  • Quaternary Ammonium Compounds/adverse effects*
  • Reactive Oxygen Species/metabolism
  • Superoxide Dismutase/genetics
  • Thioctic Acid/administration & dosage*
  • Thioctic Acid/pharmacology
  • Zebrafish
PubMed
30708965 Full text @ Int. J. Mol. Sci.
Abstract
Iron toxicity is associated with organ injury and has been reported in various clinical conditions, such as hemochromatosis, thalassemia major, and myelodysplastic syndromes. Therefore, iron chelation therapy represents a pivotal therapy for these patients during their lifetime. The aim of the present study was to assess the iron chelating properties of α-lipoic acid (ALA) and how such an effect impacts on iron overload mediated toxicity. Human mesenchymal stem cells (HS-5) and animals (zebrafish, n = 10 for each group) were treated for 24 h with ferric ammonium citrate (FAC, 120 µg/mL) in the presence or absence of ALA (20 µg/mL). Oxidative stress was evaluated by reduced glutathione content, reactive oxygen species formation, mitochondrial dysfunction, and gene expression of heme oxygenase-1b and mitochondrial superoxide dismutase; organ injury, iron accumulation, and autophagy were measured by microscopical, cytofluorimetric analyses, and inductively coupled plasma‒optical mission Spectrometer (ICP-OES). Our results showed that FAC results in a significant increase of tissue iron accumulation, oxidative stress, and autophagy and such detrimental effects were reversed by ALA treatment. In conclusion, ALA possesses excellent iron chelating properties that may be exploited in a clinical setting for organ preservation, as well as exhibiting a good safety profile and low cost for the national health system.
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