Archives of Toxicology

, Volume 80, Issue 10, pp 662–670

Molecular targets against mustard toxicity: implication of cell surface receptors, peroxynitrite production, and PARP activation

  • Ahmet Korkmaz
  • Hakan Yaren
  • Turgut Topal
  • Sukru Oter
Molecular Toxicology

DOI: 10.1007/s00204-006-0089-x

Cite this article as:
Korkmaz, A., Yaren, H., Topal, T. et al. Arch Toxicol (2006) 80: 662. doi:10.1007/s00204-006-0089-x

Abstract

Despite many years of research into chemical warfare agents, cytotoxic mechanisms induced by mustards are not well understood. Reactive oxygen and nitrogen species (ROS and RNS) are likely to be involved in chemical warfare agents induced toxicity. These species lead to lipid peroxidation, protein oxidation, and DNA injury, and trigger many pathophysiological processes that harm the organism. In this article, several steps of pathophysiological mechanisms and possible ways of protection against chemical warfare agents have been discussed. In summary, pathogenesis of mustard toxicity is explained by three steps: (1) mustard binds target cell surface receptor, (2) activates intracellular ROS and RNS leading to peroxynitrite (ONOO) production, and (3) the increased ONOO level damages organic molecules (lipids, proteins, and DNA) leading to poly(adenosine diphosphate-ribose) polymerase (PARP) activation. Therefore, protection against mustard toxicity could also be performed in these ways: (1) blocking of cell surface receptor, (2) inhibiting the ONOO production or scavenging the ONOO produced, and (3) inhibiting the PARP, activated by ONOO and hydroxyl radical (OH) induced DNA damage. As conclusion, to be really effective, treatment against mustards must take all molecular mechanisms of cytotoxicity into account. Combination of several individual potent agents, each blocking one of the toxic mechanisms induced by mustards, would be interesting. Therefore, variations of combination of cell membrane receptor blockers, antioxidants, nitric oxide synthase inhibitors, ONOO scavengers, and PARP inhibitors should be investigated.

Keywords

Nitrogen mustard Sulfur mustard Nitric oxide Peroxynitrite PARP 

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Ahmet Korkmaz
    • 1
  • Hakan Yaren
    • 2
  • Turgut Topal
    • 1
  • Sukru Oter
    • 1
  1. 1.Department of PhysiologyGulhane Military Medical AcademyEtlik/AnkaraTurkey
  2. 2.Department of Nuclear, Biologic and Chemical WarfareGulhane Military Medical AcademyEtlik/AnkaraTurkey

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