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Metals, toxicity and oxidative stress.

M Valko1, H Morris, M T D Cronin

  • 1Faculty of Chemical and Food Technology, Slovak Technical University, SK-812 37 Bratislava, Slovakia. marian.valko@stuba.sk

Current Medicinal Chemistry
|May 17, 2005
PubMed
Summary

Metals cause toxicity and cancer by generating reactive oxygen species, damaging DNA and lipids. Antioxidants like Vitamin E and C can offer protection against these harmful metal-induced effects.

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Area of Science:

  • Environmental Toxicology
  • Biochemistry
  • Carcinogenesis

Background:

  • Metal-induced toxicity and carcinogenicity are significant health concerns.
  • Reactive oxygen and nitrogen species play a crucial role in these processes.
  • Understanding the mechanisms of metal toxicity is vital for developing protective strategies.

Purpose of the Study:

  • To review the generation and role of reactive oxygen and nitrogen species in metal-induced toxicity and carcinogenicity.
  • To elucidate the mechanisms by which various metals exert their toxic effects.
  • To discuss the protective roles of antioxidants against metal-induced damage.

Main Methods:

  • Literature review of studies on metal toxicity, free radical generation, and oxidative stress.

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  • Analysis of mechanisms involving DNA damage, lipid peroxidation, and cellular homeostasis.
  • Examination of the role of specific metals (Fe, Cu, Cr, V, Co, Hg, Cd, Ni, As) and signaling pathways.

    • Main Results:

    • Metals induce toxicity and carcinogenicity via reactive oxygen and nitrogen species, leading to DNA modifications and lipid peroxidation.
    • Different metals employ distinct mechanisms, including redox-cycling or glutathione depletion.
    • Antioxidants like Vitamin E and C demonstrate protective effects against metal-induced oxidative stress, though with some caveats.

    Conclusions:

    • Reactive oxygen and nitrogen species generation is a unifying factor in metal-induced toxicity and carcinogenicity.
    • Antioxidant interventions show promise in mitigating metal-induced damage.
    • Further research is needed to fully understand metal-specific mechanisms and optimize antioxidant therapies.