Nitric oxide toxicity

K. Maiese et al.. Cellular mechanisms of protection by metabotropic glutamate receptors during anoxia and nitric oxide toxicity. J. Neurochem., 66 (1996) 2419-2428. 

Chen Y, Vartiainen NE, Ying W, Chan PH, Koistinaho J, Swanson RA (2001) Astrocytes protect neurons from nitric oxide toxicity by a glutathione-dependent mechanism. J Neurochem 77 1601-1610. 

Maiese, K., Boniece, I., Demeo, D. and Wagner, J.A. (1993) Peptide growth factors protect against ischemia in culture by preventing nitric oxide toxicity. J. Neurosci. 13 3034-3040. 

Fig. 6.4 Effect of nitric oxide toxicity on proteins, lipids, and DNA...

Heller B, Wang ZQ, Wagner EF et al. Inactivation of the poly (ADP-ribose) polymerase gene affects oxygen radical and nitric oxide toxicity in islet cells. J Biol Chem 1995 270 11176-80. 

Radons J, Heller B, Burkle A et al. Nitric oxide toxicity in islet cells involves polyfADP-ribose) polymerase activation and concomitant NAD+ depletion. Biochem Biophys Res Commun 1994 199 1270-7. 

Nitric oxide has also been implicated in PD. Thus animals with MPTP-induced Parkinsonism not only show extensive gliosis in the substantia nigra (like humans) in which the glial cells produce NO, but Liberatore and colleagues have found that in iNOS (inducible nitric oxide synthase) knock-out mice the toxicity of MPTP is halved. Since NO releases iron from ferritin and produces toxic peroxinitrate in the presence of superoxide radicals it could accelerate, even if it does not initiate, dopaminergic cell death (see Hirsch and Hunot 2000 for further details). 

Research has shown that when polychlorpinen, ammonium nitrate, and superphosphate are present together in the soil, phosgene, carbon monoxide, nitric oxide, hydrochloric acid, ammonia, hydrocyanic anions, ozone, hydrogen fluoride and phosphide, etc. could appear in the air over the beet fields. Photooxidants could also appear. Airborne toxic compounds over this crop were noted in areas after precipitation with little wind, and with an air temperature of over 2CP . The combined and complex activity of pesticides and other chemical compounds led people who manually sowed beets to develop symptoms of poisoning. [21]... 

Finally, perhaps one of the oddest of recent discoveries is that toxic gases, such as nitric oxide (NO) and carbon monoxide (CO), can act as dual first/second messengers in the nervous system (Haley, 1998). Our current ideas of how drugs affect the complex events and regulation of synaptic neurotransmission are very simplistic and the real situation is obviously vastly more complicated. Some of these issues will be addressed in more detail in Chapter 14. 

J.B. Hibbs, R.R. Taintor, Z. Vavrin, and E.M. Rachlin, Nitric-oxide — a cyto-toxic activated macrophage effector molecule. Biochem. Biophys. Res. Comnuin. 157, 87-94 (1988). 

---