0000000000223834
AUTHOR
Ana Olmos
Drugs modulating the biological effects of peroxynitrite and related nitrogen species.
The term “reactive nitrogen species” includes nitrogen monoxide, commonly called nitric oxide, and some other remarkable chemical entities (peroxynitrite, nitrosoperoxycarbonate, etc.) formed mostly from nitrogen monoxide itself in biological environments. Regardless of the specific mechanisms implicated in their effects, however, it is clear that an integrated pharmacological approach to peroxynitrite and related species is only just beginning to take shape. The array of affected chemical and pathological processes is extremely broad. One of the most conspicuous mechanisms observed thus far has been the scavenging of the peroxynitrite anion by molecules endowed with antioxidant activity. T…
Protein Tyrosine Nitration Induced by Heme/Hydrogen Peroxide: Inhibitory Effect of Hydroxycinnamoyl Conjugates
The present study was designed to optimize the experimental conditions that govern the heme-catalyzed nitration of protein tyrosine residues by nitrite, and, within this framework, to study the effects of 3,5-dicaffeoylquinic acid and its methyl ester, both of which have been previously reported to be antioxidants and inhibitors of leukocyte functions. Although the presence of hydrogen peroxide is essential in cell-free systems, an excess of this compound was found to be detrimental, so much so that an increase in hemin concentration actually resulted in an inverse effect on the reaction, depending on the levels of fixed hydrogen peroxide. Unlike previous reports on nitrite-induced albumin …
Drugs modulating the biological effects of peroxynitrite and related nitrogen species
The term “reactive nitrogen species” includes nitrogen monoxide, commonly called nitric oxide, and some other remarkable chemical entities (peroxynitrite, nitrosoperoxycarbonate, etc.) formed mostly from nitrogen monoxide itself in biological environments. Regardless of the specific mechanisms implicated in their effects, however, it is clear that an integrated pharmacological approach to peroxynitrite and related species is only just beginning to take shape. The array of affected chemical and pathological processes is extremely broad. One of the most conspicuous mechanisms observed thus far has been the scavenging of the peroxynitrite anion by molecules endowed with antioxidant activity. T…
Effects of plant alkylphenols on cytokine production, tyrosine nitration and inflammatory damage in the efferent phase of contact hypersensitivity
Background and purpose: The phenolic compounds isoprenylhydroquinone glucoside (IHG), 3,5-dicaffeoylquinic acid (DCA), and its methyl ester (DCE) have previously been shown to inhibit both contact hypersensitivity (CHS) and peroxynitrite reactivity. The present work seeks to establish a relationship between the anti-inflammatory effect and the release of cytokines and tyrosine nitration in skin. Experimental approach: Murine CHS was developed by means of sensitization and challenge with dinitrofluorobenzene (DNFB) or oxazolone. Ear swelling was measured 24 and 96 h after challenge. Interleukin (IL)-1b, IL-4, and tumour necrosis factor (TNF)-a were measured by ELISA; and the expression of in…
Isoprenylhydroquinone glucoside: a new non-antioxidant inhibitor of peroxynitrite-mediated tyrosine nitration
Abstract Three hydroquinone glucosides and four caffeoylquinic esters were examined for their effect on tyrosine nitration, as well as on the oxidation of dihydrorhodamine (DHR) 123 and cytochrome c 2+ induced by peroxynitrite. All these phenolics, which had previously been characterized as the active principles of the plant Phagnalon rupestre , were fairly active in preventing the oxidation of DHR 123, though inefficient in the cytochrome c test. While their antioxidant potency is associated with the presence of a caffeoyl moiety, not so an obvious chemical character was correlated to a greater activity against nitration of tyrosine. Here, the highest potency corresponded to 2-isoprenylhyd…
Interaction of dicaffeoylquinic derivatives with peroxynitrite and other reactive nitrogen species.
Plant phenolic antioxidants, among them catechins and hydroxycinnamoyl conjugates, constitute a well defined class of inhibitors of reactive nitrogen species (RNS). To gain deeper insight in this field, we examined the effects of 3,5-di-O-caffeoylquinic acid (DCA), its methyl ester (DCE) and epigallocatechin gallate (EGCG) in nitrative and oxidative processes. These compounds were found to be strong inhibitors of the nitration of tyrosine residues induced by ONOO- in bovine seroalbumin, with their IC50 values (10-40 microM) notably decreasing in the presence of bicarbonate. When studied on the intracellular protein tyrosine nitration induced by ONOO- in cultured murine fibroblasts as well a…
Modulation of protein tyrosine nitration and inflammatory mediators by isoprenylhydroquinone glucoside.
The nitration of tyrosine caused by peroxynitrite and other reactive nitrogen species is clearly detrimental for some physiological processes; however, its signalling role is still open to controversy. Among the natural phenolics known for their ability to oppose free tyrosine nitration, isoprenylhydroquinone glucoside is investigated due to its unusual structure, which contains a simple hydroxybenzene alkylated by a hemiterpenoid moiety. This hydroquinone was shown to be an effective inhibitor of peroxynitrite-induced protein tyrosine nitration in 3T3 fibroblasts. When tested on bovine seroalbumin nitration, however, the potency was reduced by half and the effect was almost abolished in th…