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Molecular targets against mustard toxicity: implication of cell surface receptors, peroxynitrite production, and PARP activation.
Arch Toxicol. 2006 Oct; 80(10):662-70.AT

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.

Authors+Show Affiliations

Department of Physiology, Gulhane Military Medical Academy, 06018 Etlik/Ankara, Turkey.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

16552503

Citation

Korkmaz, Ahmet, et al. "Molecular Targets Against Mustard Toxicity: Implication of Cell Surface Receptors, Peroxynitrite Production, and PARP Activation." Archives of Toxicology, vol. 80, no. 10, 2006, pp. 662-70.
Korkmaz A, Yaren H, Topal T, et al. Molecular targets against mustard toxicity: implication of cell surface receptors, peroxynitrite production, and PARP activation. Arch Toxicol. 2006;80(10):662-70.
Korkmaz, A., Yaren, H., Topal, T., & Oter, S. (2006). Molecular targets against mustard toxicity: implication of cell surface receptors, peroxynitrite production, and PARP activation. Archives of Toxicology, 80(10), 662-70.
Korkmaz A, et al. Molecular Targets Against Mustard Toxicity: Implication of Cell Surface Receptors, Peroxynitrite Production, and PARP Activation. Arch Toxicol. 2006;80(10):662-70. PubMed PMID: 16552503.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular targets against mustard toxicity: implication of cell surface receptors, peroxynitrite production, and PARP activation. AU - Korkmaz,Ahmet, AU - Yaren,Hakan, AU - Topal,Turgut, AU - Oter,Sukru, Y1 - 2006/03/22/ PY - 2005/11/29/received PY - 2006/02/28/accepted PY - 2006/3/23/pubmed PY - 2007/2/3/medline PY - 2006/3/23/entrez SP - 662 EP - 70 JF - Archives of toxicology JO - Arch Toxicol VL - 80 IS - 10 N2 - 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. SN - 0340-5761 UR - https://www.unboundmedicine.com/medline/citation/16552503/Molecular_targets_against_mustard_toxicity:_implication_of_cell_surface_receptors_peroxynitrite_production_and_PARP_activation_ L2 - https://doi.org/10.1007/s00204-006-0089-x DB - PRIME DP - Unbound Medicine ER -