Scavenging of Cation Radicals of the Visual Cycle Retinoids by Lutein, Zeaxanthin, Taurine, and Melanin.

In the retina, retinoids involved in vision are under constant threat of oxidation, and their oxidation products exhibit deleterious properties. Using pulse radiolysis, this study determined that the bimolecular rate constants of scavenging cation radicals of retinoids by taurine are smaller than 2 × 107 M-1s-1 whereas lutein scavenges cation radicals of all three retinoids with the bimolecular rate constants approach the diffusion-controlled limits, while zeaxanthin is only 1.4-1.6-fold less effective. Despite that lutein exhibits greater scavenging rate constants of retinoid cation radicals than other antioxidants, the greater concentrations of ascorbate in the retina suggest that ascorbate may be the main protectant of all visual cycle retinoids from oxidative degradation, while α-tocopherol may play a substantial role in the protection of retinaldehyde but is relatively inefficient in the protection of retinol or retinyl palmitate. While the protection of retinoids by lutein and zeaxanthin appears inefficient in the retinal periphery, it can be quite substantial in the macula. Although the determined rate constants of scavenging the cation radicals of retinol and retinaldehyde by dopa-melanin are relatively small, the high concentration of melanin in the RPE melanosomes suggests they can be scavenged if they are in proximity to melanin-containing pigment granules.

COVID-19 and the ethnicity link - is there a photochemical link?

A hypothesis is proposed to explain the increased detrimental effect of COVID-19 for Black, Asian and Minority Ethnic (BAME) men and women compared to Caucasian individuals. This is based on the differing photochemistry of phaeomelanin in fair skin and eumelanin in dark/black skin. It is suggested that a range of reactive oxygen species, including, singlet oxygen and the superoxide radical anion, derived via direct photolysis of phaeomelanin, may escape the melanocyte and cause subsequent damage to the SARS-CoV-2 virus. It is further suggested that (large) carbon and sulphur peroxy radicals, from oxygen addition to radicals formed by carbon-sulphur bond cleavage, may assist via damage to the cell membranes. It is also speculated that light absorption by phaeomelanin and the subsequent C-S bond cleavage, leads to release of pre-absorbed reactive oxygen species, such as singlet oxygen and free radicals, which may also contribute to an enhanced protective effect for fair-skinned people.

Anti- and pro-oxidative mechanisms comparing the macular carotenoids zeaxanthin and lutein with other dietary carotenoids - a singlet oxygen, free-radical in vitro and ex vivo study.

The interactions of dietary carotenoids, and particularly the xanthophylls in the macula, with singlet oxygen and three different oxy-radicals, (hydroxyl radical, nitrogen dioxide and the superoxide radical anion) are compared using pulsed laser and γ-techniques. The results give possible molecular mechanisms for the switch from anti-oxidant (protection) by carotenoids to pro-oxidant (damage) by carotenoids. The participation of oxygen in radical mechanisms in the presence of different carotenoids is compared for the different radicals. It is shown that the mechanistic role of oxygen differs very significantly for anti-/pro-oxidation by hydroxyl radicals when compared to nitrogen dioxide. Lutein was found to be an extremely good cell protector against hydroxyl radicals at all oxygen concentrations, including under physiological conditions.

The Benefits and Risks of Certain Dietary Carotenoids that Exhibit both Anti- and Pro-Oxidative Mechanisms-A Comprehensive Review.

Carotenoid pigments, particularly ß-carotene and lycopene, are consumed in human foodstuffs and play a vital role in maintaining health. ß-carotene is known to quench singlet oxygen and can have strong antioxidant activity. As such, it was proposed that ß-carotene might reduce the risk of cancer. Epidemiological studies found inverse relationships between cancer risk and ß-carotene intake or blood levels. However, clinical trials failed to support those findings and ß-carotene supplementation actually increased lung cancer incidence in male smokers. Early experimental animal studies found dietary ß-carotene inhibited UV-induced skin cancers. Later studies found that ß-carotene supplementation exacerbated UV-carcinogenic expression. The discrepancies of these results were related to the type of diet the animals consumed. Lycopene has been associated with reduced risk of lethal stage prostate cancer. Other carotenoids, e.g., lutein and zeaxanthin, play a vital role in visual health. Numerous studies of molecular mechanisms to explain the carotenoids' mode of action have centered on singlet oxygen, as well as radical reactions. In cellular systems, singlet oxygen quenching by carotenoids has been reported but is more complex than in organic solvents. In dietary ß-carotene supplement studies, damaging pro-oxidant reactivity can also arise. Reasons for this switch are likely due to the properties of the carotenoid radicals themselves. Understanding singlet oxygen reactions and the anti-/pro-oxidant roles of carotenoids are of importance to photosynthesis, vision and cancer.

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

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 ß-, 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).

Singlet Oxygen and Free Radical Reactions of Retinoids and Carotenoids-A Review.

We report on studies of reactions of singlet oxygen with carotenoids and retinoids and a range of free radical studies on carotenoids and retinoids with emphasis on recent work, dietary carotenoids and the role of oxygen in biological processes. Many previous reviews are cited and updated together with new data not previously reviewed. The review does not deal with computational studies but the emphasis is on laboratory-based results. We contrast the ease of study of both singlet oxygen and polyene radical cations compared to neutral radicals. Of particular interest is the switch from anti- to pro-oxidant behavior of a carotenoid with change of oxygen concentration: results for lycopene in a cellular model system show total protection of the human cells studied at zero oxygen concentration, but zero protection at 100% oxygen concentration.

Interactions of dietary carotenoids with singlet oxygen (1O2) and free radicals: potential effects for human health.

The dietary carotenoids provide photoprotection to photosynthetic organisms, the eye and the skin. The protection mechanisms involve both quenching of singlet oxygen and of damaging free radicals. The mechanisms for singlet oxygen quenching and protection against free radicals are quite different - indeed, under some conditions, quenching of free radicals can lead to a switch from a beneficial anti-oxidant process to damaging pro-oxidative situation. Furthermore, while skin protection involves ß-carotene or lycopene from a tomato-rich diet, protection of the macula involves the hydroxyl-carotenoids (xanthophylls) zeaxanthin and lutein. Time resolved studies of singlet oxygen and free radicals and their interaction with carotenoids via pulsed laser and fast electron spectroscopy (pulse radiolysis) and the possible involvement of amino acids are discussed and used to (1) speculate on the anti- and pro-oxidative mechanisms, (2) determine the most efficient singlet oxygen quencher and (3) demonstrate the benefits to photoprotection of the eye from the xanthophylls rather than from hydrocarbon carotenoids such as ß-carotene.

Prooxidant and antioxidant behaviour of usnic acid from lichens under UVB-light irradiation--studies on human cells.

Natural compounds which can behave as antioxidants and protect against UV-radiation may well have medical and cosmetic value. Usnic acid, which can be obtained from lichens offer such a potential. The latter is one of the best known and reviewed compounds present in lichens and exhibits many properties of value such as antibiotic, antitumor and UV-filter-effects. We report studies of the potential antioxidant and prooxidant activity of usnic acid extracted from Xanthoparmelia farinosa (Vainio) using a human lymphocyte cell line (Jurkat-cells) under UV-B-irradiation. Cell survival and cell metabolism were determined using different conditions such as usnic acid concentration and UVB dose. Compared to the controls the cells incubated with usnic acid in concentrations of 1 x 10(-8) and 1 x 10(-6) M showed a higher cell survival and a normal metabolism under low doses of UVB-light up to 0.1 J/cm(2). When both higher UVB doses (up to 14 J/cm(2)) and higher concentrations of usnic acid (1 x 10(-4) M) where used, the opposite effect was observed. It is concluded that these effects are due to bifunctional (a switch of) anti-oxidative-pro-oxidative behaviour of usnic acid under UV-B-irradiation.

Lichens--photophysical studies of potential new sunscreens.

Fundamental photophysical properties have been obtained for six polyaromatics, calycine, usnic acid, vicanicine, 1-Cl-pannerine and epiphorelic acids I and II, extracted from Antarctic lichens--potential future sunscreens. None of the lichen compounds produced a measurable amount of triplet states and the singlet oxygen quantum yield was also very low ranging from 0.003 to 0.06. However, three exhibited triplet energy levels which may be above that of thymine. The radical cations of calycine and usnic acid were generated via pulse radiolysis and were observed to be quenched by vitamin C, vitamin E and Trolox.

Carotenoid radical anions and their protonated derivatives.

In this study, we report the protonation reactions for astaxanthin and canthaxanthin radical anions in methanol, alkaline methanol, and aqueous 2% Triton X-100 at different pH values. The pKa values for the corresponding alpha-hydroxy radical derivatives of astaxanthin, canthaxanthin, and beta-apo-8'-carotenal were estimated in 2% Triton X-100. Also, the effects of the microenvironment and the structure of the carotenoids on the protonation rate constant are discussed.

Pulse radiolysis study of the interaction of retinoids with peroxyl radicals.

Vitamin A (retinol) and its derivatives-retinal and retinoic acid-are known for their ability to inhibit lipid peroxidation. Antioxidant actions of retinoids have been attributed to chain-breaking by scavenging of peroxyl radicals. Based on chemical analysis of retinoic acid degradation products formed during microsomal lipid peroxidation, it was previously suggested that retinoids interact with peroxyl radicals forming free carbon-centered radical adducts. However, it can be argued that such a mode of antioxidant action of retinoids is not sufficient to fully explain their effectiveness at inhibiting lipid peroxidation, which in many systems is comparable to, or even exceeds, that of alpha-tocopherol. In order to elucidate the mechanism of interaction of retinoids with peroxyl radicals, (trichloromethyl)peroxyl radical was generated by pulse radiolysis, and its interactions with retinoids solubilized in Triton X-100 micelles were followed by kinetic absorption spectroscopy. All retinoids--retinol, retinal, and retinoic acid--interacted with the peroxyl radical, and at least two transient products were detected. One of these products, absorbing at 590 nm, was identified as retinoid cation radical. Therefore, we postulate that, apart from formation of radical adducts, retinoids may also scavenge peroxyl radicals by electron transfer.

Spectroscopic properties and reactivity of free radical forms of A2E.

A pyridinium bisretinoid (A2E) is the only identified blue-absorbing chromophore of retinal lipofuscin that has been linked to its aerobic photoreactivity and phototoxicity. Pulse radiolysis has been used to study both the one-electron oxidation and the one-electron reduction of A2E in aqueous micellar solutions. The reduction to the semireduced A2E (lambda(max) broad and between 500 and 540 nm) was achieved with formate radicals and the subsequent decay of A2E* was slow (over hundreds of milliseconds) via complex kinetics. The long lifetime of the A2E* should facilitate its reactions with other biomolecules. For example, with oxygen, the A2E* produced the superoxide radical anion with a rate constant of 3 x 10(8) M(-1) s(-1). The A2E was also reduced by the NAD radical, the corresponding rate constant being 2.3 x 10(8) M(-1) s(-1). Other experiments showed that the one-electron reduction potential of A2E lies in the range -640 to -940 mV. The semioxidized form of A2E (lambda(max) 590 nm) was formed via oxidation with the Br2*- radical and had a much shorter lifetime than the semireduced form. With strongly oxidizing peroxyl radicals (CCl3O2*) our kinetic data suggest the formation of a radical adduct followed by dissociation to the semioxidized A2E. With milder oxidizing peroxyl radicals such as that from methanol, our results were inconclusive. In benzene we observed an efficient oxidation of zeaxanthin to its radical cation by the A2E radical cation; this may be relevant to a detrimental effect of A2E in vision.

Are dietary carotenoids beneficial? Reactions of carotenoids with oxy-radicals and singlet oxygen.

Carotenoids play diverse roles in biology and medicine. Both the quenching of singlet oxygen (energy transfer) and interaction with oxy-radicals (electron transfer, H-atom transfer and addition reactions) are key processes in understanding many of these roles. Much previous work in 'simple' solvents is reviewed and new results in cell membrane models are presented. The possible consequences of using carotenoids as dietary supplements are discussed.

Carotenoid radical chemistry and antioxidant/pro-oxidant properties.

The purpose of this review is to summarise the current state of knowledge of (i) the kinetics and mechanisms of radical reactions with carotenoids, (ii) the properties of carotenoid radicals, and (iii) the antioxidant/pro-oxidant properties of carotenoids.

Cooperation of antioxidants in protection against photosensitized oxidation.

The aim of this study was to determine whether alpha-tocopherol and zeaxanthin offer synergistic protection against photosensitized lipid peroxidation mediated by singlet oxygen and free radicals. The antioxidant action of zeaxanthin and alpha-tocopherol was studied in liposomes made of phosphatidylcholine and cholesterol. Progress of lipid peroxidation, induced by aerobic photoexcitation of rose bengal, was monitored by the detection of lipid hydroperoxides and by electron spin resonance oximetry. In addition, cholesterol was employed as a mechanistic reporter molecule, which forms characteristic products of the interaction with singlet oxygen or free radicals. Cholesterol hydroperoxides were quantitatively determined by HPLC/electrochemical detection. HPLC/ultraviolet-visible (UV-VIS) absorption detection was used to measure concentrations of zeaxanthin and alpha-tocopherol. Zeaxanthin, even at concentrations of 2.5 microM, effectively protected against singlet oxygen-mediated lipid peroxidation but was rapidly consumed due to interaction with free radicals. alpha-Tocopherol alone was not effective in protecting against lipid peroxidation, even at concentration of 0.1 mM. Combinations of zeaxanthin and alpha-tocopherol exerted a synergistic protection against lipid peroxidation. The synergistic effect may be explained in terms of prevention of carotenoid consumption by effective scavenging of free radicals by alpha-tocopherol therefore allowing zeaxanthing to quench the primary oxidant-singlet oxygen effectively.

Singlet oxygen quenching by dietary carotenoids in a model membrane environment.

The ability of several dietary carotenoids to quench singlet oxygen in a model membrane system (unilamellar DPPC liposomes) has been investigated. Singlet oxygen was generated in both the aqueous and the lipid phase, with quenching by a particular carotenoid independent of the site of generation. However, singlet oxygen quenching is dependent on the carotenoid incorporated; xanthophylls exhibit a marked reduction in efficiency compared to the hydrocarbon carotenoids. Lycopene and beta-carotene exhibit the fastest singlet oxygen quenching rate constants (2.3-2.5 x 10(9)M(-1)s(-1)) with lutein the least efficient (1.1 x 10(8)M(-1)s(-1)). The other carotenoids, astaxanthin and canthaxanthin, are intermediate. Zeaxanthin exhibits anomalous behavior, and singlet oxygen quenching decreases with increasing amounts of zeaxanthin, leading to nonlinear plots for the decay of singlet oxygen with zeaxanthin concentration. Such differences are discussed in terms of carotenoid structure and their influence on the properties of the lipid membrane. The formation of aggregates by the polar carotenoids is also proposed to be of significance in their ability to quench singlet oxygen.