Antioxidant activities of some tryptophan metabolites: possible implication for inflammatory diseases.

Abstract

The antioxidant properties of tryptophan and some of its oxidative metabolites were examined by measuring how efficiently they inhibited peroxyl radical-mediated oxidation of phosphatidyicholine liposomes and B-phycoerythrin.Low micromolar concentrations of 5-hydroxytryptophan, 3-hydroxykynurenine, xanthurenic acid, or 3-hydroxyanthranilic acid, but not their corresponding nonhydroxylated metabolic precursors, scavenged peroxyl radicals with high efficiency. In particular, 3-hydroxykynurenine and 3-hydroxyanthranilic acid protected B-phycoerythrin from peroxyl radical-mediated oxidative damage more effectively than equimolar amounts of either ascorbate or Trolox (a water-soluble analog of vitamin E). Enzyme activities involved or related to oxidative tryptophan metabolism, as well as endogenous concentrations of tryptophan and its metabolites, were determined within tissues of mice suffering from acute viral pneumonia.

IFN-γ ameliorates autoimmune encephalomyelitis by limiting myelin lipid peroxidation

“…However, specifically in macrophages and microglia, IFN-γ additionally induces the production of the metabolite 3-hydroxyanthranilic acid (3-HAA), a powerful antioxidant (34). Because 3-HAA is a robust free-radical scavenger (17), it was previously proposed that induction of this pathway by IFN-γ may represent a localized, extracellular antioxidant defense to protect host tissue from inadvertent oxidative damage that could occur during inflammatory conditions. This concept is in agreement with our studies, in which we found that the absence of IFN-γ signaling during EAE resulted in significantly enhanced lipid peroxidation products, as compared with WT mice, and corresponded to a more severe disease course that proceeded to a chronic inflammatory state.…”

“…Our results thus far strongly indicated a role for IFN-γ in limiting disease in EAE via modulating myelin Ag uptake and the removal of free myelin Ag by CNS APCs. It has been suggested previously that IFN-γ potentially could limit tissue damage during inflammation by limiting oxidative processes such as peroxidation of lipids (17). Myelin is lipid-rich; thus it was conceivable that peroxidation of lipids and/or proteins could be increased in the CNS of animals with disrupted IFN-γ signaling during EAE, in particular during the chronic phase of disease.…”

“…Along these lines, it has been reported that cytokines such as IFN-γ can stimulate microglia and macrophages to break down oxidized lipids as a self-limiting mechanism to prevent host tissue from inadvertent oxidative damage (17).…”

Indoleamine 2,3-Dioxygenase Expression in Transplanted NOD Islets Prolongs Graft Survival After Adoptive Transfer of Diabetogenic Splenocytes

“…Localized depletion of tryptophan in vivo has also been implicated in the immune evasion of certain tumors (9,10). Indoleamine 2,3-dioxygenase (IDO), the enzyme that regulates the rate-limiting step involved in the catabolism of tryptophan to kyneurenine, is also involved in the control of microbial infections (11)(12)(13)(14) and has been shown to have antioxidant properties (15)(16)(17). Pregnancy maintenance has also been associated with tryptophan catabolism by preventing the proliferation of maternal T-cells in response to tissues of the fetus expressing HLA alleles of the father (18).…”

Towards amino acid recommendations for specific physiological and patho-physiological states in pigs

“…Finally, IDO induction during immune activation may protect cells from oxidative damage (87) . Indeed, 3-hydroxyanthranilic acid and 3-hydroxykynurenine, produced from tryptophan through the IDO-kynurenine pathway, have antioxidant properties (88) . This suggests that dietary tryptophan could influence the inflammatory response and the animal health.…”