Cytotoxicity of Nitric Oxide and Hydrogen Peroxide

Is There a Cooperative Action?
  • Iosif Ioannidis
  • Thomas Volk
  • Herbert de Groot
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 387)


Nitric oxide (·NO) is well defined as an important effector molecule in biological systems. Secreted from various cell types, ·NO contributes to a variety of physiological and pathophysiological processes [22]. Despite of its function in the control of blood pressure, platelet aggregation and neurotransmission, which are mediated via the activation of the soluble guanylate cyclase, ·NO has been shown to be a potent modulator of the cytotoxic activity of macrophages as well [12; 21]. The mechanisms by which the bactericidal and the tumoricidal potential of ·NO is defined are still poorly understood. Diverse molecular targets have been postulated to exist for an attack of ·NO on the cell surface as well as inside the cells such as thiol groups of proteins yielding S-nitrosothiols [14]. In addition to the membrane-linked targets, ·NO is suggested to inhibit the mitochondrial respiratory chain, DNA and protein synthesis and iron metabolism [11]. Besides these effects, which could be defined as direct effects of ·NO, an increasing number of studies postulates that the cytotoxicity of ·NO is enhanced by chemical interactions with oxygen and reactive oxygen species to form other potentially toxic radicals. For example, ·NO reacts with the superoxide anion (O2 ) forming the peroxynitrite anion (ONOO) which decays, once protonated, to the very reactive hydroxyl radical (·OH) and to nitrogen dioxide (·NO2) [1]. Increased reactivity due to an interplay of ·NO with O2 via the ONOO pathway is supported by studies in biological as well as in chemical systems [28; 25; 4; 5].


Nitric Oxide Mitochondrial Respiratory Chain Nitrogen Dioxide Sinusoidal Endothelial Cell Soluble Guanylate Cyclase 


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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Iosif Ioannidis
    • 1
  • Thomas Volk
    • 2
  • Herbert de Groot
    • 1
  1. 1.Institut für Physiologische ChemieUniversitätsklinikumEssenGermany
  2. 2.Abteilung für Anesthäsiologie und IntensivmedizinUniversitätsklinikum CharitéBerlinGermany

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