Role of Xanthurenic Acid 8-O-β-d-Glucoside, a Novel Fluorophore that Accumulates in the Brunescent Human Eye Lens¶

Abstract

We have been able to identify a blue fluorophore from the low‐molecular weight soluble fraction of human adult nondiabetic brunescent cataract lenses as xanthurenic acid 8‐O‐β‐d‐glucoside (XA8OG) (excitation = 338 nm and emission = 440 nm). To determine the role of this fluorophore in the lens, we have examined its photophysical and photodynamic properties. We found XA8OG to have a fluorescence quantum yield (ϕ) of 0.22 and a major emission lifetime of 12 ns. We found it to be a UVA‐region sensitizer, capable of efficiently generating singlet oxygen species but little of superoxide. We also demonstrated that XA8OG oxidizes proteins when irradiated with UVA light, causing photodynamic covalent chemical damage to proteins. Its accumulation in the aging human lens (and the attendant decrease of its precursor O‐β‐d‐glucoside of 3‐hydroxykynurenine) can, thus, add to the oxidative burden on the system. XA8OG, thus, appears to be an endogenous chromophore in the lens, which can act as a cataractogenic agent.

Prooxidant action of xanthurenic acid and quinoline compounds: Role of transition metals in the generation of reactive oxygen species and enhanced formation of 8-hydroxy-2′-deoxyguanosine in DNA†

“…Xanthurenic acid is related to various pathological conditions (Rogers & Mohan 1994;Malina & Martin 1996;Malina 1999;Roberts et al 2000Roberts et al , 2001Thiagarajan et al 2002), although the biological function of this compound remains obscure. Xanthurenic acid production is increased by tryptophan administration (Forrest et al 2004) and vitamin B 6 deficiency in humans and animals (Adams et al 1976).…”

“…Several reports were presented concerning the tryptophan loading-mediated oxidative stress and the role of xanthurenic acid in the pathogenesis of diabetic states (Rogers & Mohan 1994) and senile cataract (Malina & Martin 1996;Malina 1999). Recently xanthurenic acid was shown to be photochemically active, and to photooxidize lens proteins in eye (Roberts et al 2000): the oxidizable properties of xanthurenic acid were discussed to be related to the cataractogenesis (Roberts et al 2001;Thiagarajan et al 2002). Xanthurenic acid with quinoline ring acts as a potent iron chelator (O'Sullivan & Smithers 1979), and some metalchelate complexes are capable of forming reactive oxygen species (Welch et al 2002), we here analyzed the xanthurenic acid/iron-mediated generation of reactive oxygen species, which was proved by the inactivation of aconitase (EC 4.2.1.3) the sensitive enzyme to active oxygen.…”

Ultraviolet Radiation as a Risk Factor for Cataract and Macular Degeneration

“…At the same time, the protective pigments are chemically modified, and now, these ocular pigments damage the lens and retina on exposure to ambient radiation. 15,16 …”

Photodynamics of Cataract: An Update on Endogenous Chromophores and Antioxidants¶

“…The details of the work up of teh isolated lenses and fractionation of the water soluble and protein‐bound accuamulants using HPLC have been described in our earlier papers (7, 8). The methods of measuring the photodynamic abilites of these compounds have also been described earlier (9, 10). Briefly.…”