Scavengers for peroxynitrite: Inhibition of tyrosine nitration and oxidation with tryptamine derivatives, alpha-lipoic acid and synthetic compounds

The inhibitory effects of various endogenous and synthetic compounds on the nitration and oxidation of L-tyrosine by peroxynitrite were examined. Nitr ating and oxidizing activities were monitored by the formation of 3-nitroty rosine and dityrosine with a HPLC-W-fluorescence detector system, respectiv ely, Glutathione, serotonin and synthetic sulfur- and selenium-containing c ompounds inhibited both the nitration and oxidation reaction of L-tyrosine effectively. However, 5-methoxytryptamine, melatonin and alpha-lipoic acid only inhibited the nitration reaction, and enhanced the formation of an oxi dation product. This is important evidence that there are different interme diates in the nitrating and oxidizing reactions of L-tyrosine by peroxynitr ite, It was suggested that 5-methoxytryptamine, melatonin and alpha-lipoic acid reacted only with the nitrating intermediate of peroxynitrite and inhi bited nitration of L-tyrosine, Actually, the DNA strand breakage, which is believed to be a typical reaction of hydroxyl radical-like species, caused by peroxynitrite was not effectively inhibited by 5-methoxytryptamine. 5-Me thoxytryptamine, melatonin and alpha-lipoic acid were viewed as useful reag ents for investigating the mechanisms of damage by peroxynitrite in vitro.