Redox Active Transition Metal ions Make Melanin Susceptible to Chemical Degradation Induced by Organic Peroxide

Abstract

With aging, retinal pigment epithelium melanosomes, by fusion with the age pigment lipofuscin, form complex granules called melanolipofuscin. Lipofuscin granules may contain oxidized proteins and lipid hydroperoxides, which in melanolipofuscin could chemically modify melanin polymer, while transition metal ions present in melanin can accelerate such oxidative modifications. The aim of this research was to examine the effect of selected transition metal ions on melanin susceptibility to chemical modification induced by the water-soluble tert-butyl hydroperoxide used as an oxidizing agent. Synthetic melanin obtained by DOPA autooxidation and melanosomes isolated from bovine retinal pigment epithelium were analyzed. To monitor tert-butyl hydroperoxide-induced oxidative changes of DMa and BMs, electron paramagnetic resonance spectroscopy, UV-vis absorption spectroscopy, dynamic light scattering, atomic force microscopy and electron paramagnetic resonance oximetry were employed. These measurements revealed that both copper and iron ions accelerated chemical degradation induced by tert-butyl hydroperoxide, while zinc ions had no effect. Strong prooxidant action was detected only in the case of melanosomes and melanin degraded in the presence of iron. It can be postulated that similar chemical processes, if they occur in situ in melanolipofuscin granules of the human retinal pigment epithelium, would modify antioxidant properties of melanin and its reactivity.

Interaction of iron ions with melanin

“…This melanin precipitated only in the acidic pH. At neutral pH it was soluble in water, the size of particles of DMa was determined to be about 20 nm (Zadlo et al, 2017) and melanin did not show any tendency to aggregate.…”

“…A control sample without iron was prepared in a similar manner except for the addition of citrate without iron. Preparation of iron complex with melanin using iron (II) salt without citrate and ADP was done as described in (Zadlo et al, 2017). In brief, such amount of water and 0.025 M ferrous sulphate in 10 -4 M H 2 SO 4 was added to 4 mg/ml melanin adjusted to pH 5 that the final melanin concentration was 2 mg/ml and iron concentration was 0.358 mM i.e.…”

Unexpected impact of esterification on the antioxidant activity and (photo)stability of a eumelanin from 5,6‐dihydroxyindole‐2‐carboxylic acid

“…The superior antioxidant potency of DHICA as well as of the synthetic DHICA melanin has been documented in vitro (Panzella et al, 2011(Panzella et al, , 2013 and in vivo (Jiang et al, 2010;Kovacs et al, 2012) ions in the system (Buszman et al, 2006;Sarna, 1992;Szpoganicz, Gidanian, Kong, & Farmer, 2002;Zadlo, Pilat, Sarna, Pawlak, & Sarna, 2017;Zdybel, Pilawa, Buszman, & Wrześniok, 2013). Indeed, di-and tripositive metal ions have been shown to bind to o-semiquinone radical centers within melanin polymers to yield chelate complexes, thus inducing a shift in the comproportionation equilibrium, which results in the increase in total radical concentration.…”

The Ability of Functionalized Fullerenes and Surface‐Modified TiO2 Nanoparticles to Photosensitize Peroxidation of Lipids in Selected Model Systems

“…Preparation of synthetic eumelanin. The synthetic model of eumelanin (DMa) was prepared by autoxidation of DOPA as described elsewhere (44).…”