Rafael Radi

TL;DR: This Review focuses on pharmacological strategies to attenuate the toxic effects of peroxynitrite, which include its catalytic reduction to nitrite and its isomerization to nitrate by metalloporphyrins, which have led to potential candidates for drug development for cardiovascular, inflammatory and neurodegenerative diseases.

TL;DR: Although protein tyrosine nitration is a low-yield process in vivo, 3-nitrotyrosine has been revealed as a relevant biomarker of •NO-dependent oxidative stress; additionally, site-specific nitration focused on particularprotein tyrosines may result in modification of function and promote a biological effect.

TL;DR: It is reported that peroxynitrite exposure to rat heart mitochondria resulted in significant inactivation of electron carriers such as succinate dehydrogenase and NADH dehydrogenases as well as the mitochondrial ATPase, indicating that mitochondria may constitute a key intracellular loci for the toxic effects of peroxysitrite under the various pathological conditions in which each appears to play a contributory role.

TL;DR: This review provides the conceptual framework and a comprehensive analysis of the current experimental strategies that can serve to unequivocally define the existence and quantitation of peroxynitrite in biological systems of different levels of organization and complexity.

TL;DR: Even though nitric oxide can directly cause a transient inhibition of electron transport, the inhibition pattern of mitochondrial respiration observed in the presence of peroxynitrite is the one that closely resembles that found secondary to .NO interactions with intact cells and strongly points to peroxlynitrite as the ultimate reactive intermediate accounting for nitricoxide-dependent inactivation of electron Transport components and ATPase in living cells and tissues.