Scavenging of Retinoid Cation Radicals by Urate, Trolox, and α-, β-, γ-, and δ-Tocopherols

Abstract

Retinoids are present in human tissues exposed to light and under increased risk of oxidative stress, such as the retina and skin. Retinoid cation radicals can be formed as a result of the interaction between retinoids and other radicals or photoexcitation with light. It has been shown that such semi-oxidized retinoids can oxidize certain amino acids and proteins, and that α-tocopherol can scavenge the cation radicals of retinol and retinoic acid. The aim of this study was to determine (i) whether β-, γ-, and δ-tocopherols can also scavenge these radicals, and (ii) whether tocopherols can scavenge the cation radicals of another form of vitamin A—retinal. The retinoid cation radicals were generated by the pulse radiolysis of benzene or aqueous solution in the presence of a selected retinoid under oxidizing conditions, and the kinetics of retinoid cation radical decays were measured in the absence and presence of different tocopherols, Trolox or urate. The bimolecular rate constants are the highest for the scavenging of cation radicals of retinal, (7 to 8) × 109 M−1·s−1, followed by retinoic acid, (0.03 to 5.6) × 109 M−1·s−1, and retinol, (0.08 to 1.6) × 108 M−1·s−1. Delta-tocopherol is the least effective scavenger of semi-oxidized retinol and retinoic acid. The hydrophilic analogue of α-tocopherol, Trolox, is substantially less efficient at scavenging retinoid cation radicals than α-tocopherol and urate, but it is more efficient at scavenging the cation radicals of retinoic acid and retinol than δ-tocopherol. The scavenging rate constants indicate that tocopherols can effectively compete with amino acids and proteins for retinoid cation radicals, thereby protecting these important biomolecules from oxidation. Our results provide another mechanism by which tocopherols can diminish the oxidative damage to the skin and retina and thereby protect from skin photosensitivity and the development and/or progression of changes in blinding retinal diseases such as Stargardt’s disease and age-related macular degeneration (AMD).

The Effect of Antioxidants on Photoreactivity and Phototoxic Potential of RPE Melanolipofuscin Granules from Human Donors of Different Age

“…In several model systems it was also demonstrated that antioxidant protection increased synergistically when combination of carotenoids and vitamin E was used [28][29][30]. Importantly, carotenoids are among the most efficient quenchers of singlet oxygen, while vitamin E is an efficient scavenger of peroxyl radicals [31][32][33][34]. Synergistic protection by zeaxanthin and vitamin E against photic stress in ARPE-19 cells, mediated by photosensitizing dyes [35], lipofuscin granules [13], or melanosomes [36], was shown in our previous studies.…”

Iron Accumulation and Lipid Peroxidation in the Aging Retina: Implication of Ferroptosis in Age-Related Macular Degeneration

“…Under photo-oxidative conditions, heme oxygenase 1 is upregulated and catalyzes the production of ferrous iron and carbon monoxide, which may exacerbate cellular injury and oxidative stress by generating free radicals [30], further enhancing the vulnerability of the retina to oxidative stress and suggesting a feed-forward cycle of photo-oxidative stress-induced damage [30]. High antioxidant content in the retina (e.g., GSH, vitamin E and C, and macular carotenoids) may counteract light-induced oxidative damage [135][136][137]. Interestingly, intracellular iron triggers the regulatory effect of glutamate synthesis and secretion in RPE cells through its effects on cytosolic aconitase activity [138][139][140].…”

Is There an Optimal Combination of AREDS2 Antioxidants Zeaxanthin, Vitamin E and Vitamin C on Light-Induced Toxicity of Vitamin A Aldehyde to the Retina?

“…Alpha-tocopherol is a well-known free radical scavenger that can effectively inhibit lipid peroxidation, acting as a chain-breaking antioxidant [ 49 ]. It can also reduce semi-oxidized lutein, zeaxanthin and ATR to their original states [ 42 , 43 , 46 , 50 ]. Alpha-tocopherol is the main tocopherol present in human tissues, including the retina [ 38 , 51 , 52 , 53 , 54 ].…”

“…As a result of interaction with singlet oxygen, hydrogen peroxide is formed, and ascorbate is oxidized to dehydroascorbate. Ascorbate can scavenge free radicals, including tocopheroxyl radical, and carotenoid and retinoid radical cations, thereby restoring these lipophilic antioxidants to the original state [ 42 , 43 , 46 , 49 , 50 , 62 ]. However, ascorbate can exert pro-oxidant effects in the presence of redox active metal ions such as iron by reducing these metal ions and thereby enabling them to function as catalysts of the Fenton reaction, where the reduced metal ion decomposes the hydrogen peroxide, leading to the formation of the most reactive free radical—the hydroxyl radical.…”