Neuromelanin is an amorphous pigment of the catecholamine origin that accumulates in certain dopaminergic neurons of the substantia nigra of human brain. In Parkinson's disease, there appears to be selective degeneration of the most heavily pigmented neurons of the substantia nigra, and this process has been linked to the presence of neuromelanin. It has been postulated that neuromelanin could increase the risk of oxidative stress reactions. On the other hand, melanin is usually considered to be an efficient antioxidant. Here we analyze experimental conditions that stimulate, or inhibit, antioxidant properties of neuromelanin. Using electron spin resonance (ESR)--spin trapping technique and salicylate hydroxylation assay, we monitored the formation of free hydroxyl radicals generated by a Fenton system in the presence of varying concentration of dopamine-melanin, a synthetic model for neuromelanin. Our data clearly indicate that the antioxidant action of neuromelanin is predominantly due to its ability to sequester redox-active metal ions such as iron. Using direct ESR spectroscopy, we have shown that ferric complexes with neuromelanin are resistant to reduction by mild biological reductants such as ascorbate. We have demonstrated that dopamine-melanin saturated with ferric ions, could enhance the formation of free hydroxyl radicals by redox activation of the ions. Thus, under the conditions that stimulate the release of accumulated metal ions, neuromelanin may actually become an efficient prooxidant. It is conceivable that neuromelanin, which normally is able to protect pigmented dopaminergic neurons against metal-ion related toxicity, could under extreme conditions have a cytotoxic role.
To determine the role of major chromophores of the human retinal pigment epithelium (RPE) in photooxidation of ascorbate, we monitored spectrophotometrically rates of ascorbate depletion, induced by blue light, in suspensions of human RPE melanin, melanolipofuscin and lipofuscin and in preparation of pigmented and nonpigmented bovine RPE cells. The results clearly show that melanin is the key retinal pigment responsible for the photosensitized oxidation of exogenous ascorbate. To elucidate the mechanism of the photooxidation process, we used purified RPE melanin granules and synthetic dopa (dihydroxyphenylalanine) melanin and employed electron spin resonance (ESR) spectroscopy, ESR oximetry and oxidase electrode. Our data indicate that photoinduced melanin radicals oxidize ascorbate via one-electron transfer reaction. The reduced melanin is reoxidized by molecular oxygen with the formation of superoxide anion and hydrogen peroxide, while the ascorbate radicals decay by disproportionation. Because in the absence of oxygen, no measurable oxidation of ascorbate is observed, it can be concluded that melanin acts as an electron transfer agent. Biological implications of this study remain unclear; however, the formation of oxygen-reactive species that accompany melanin-mediated photooxidation of ascorbate may represent a potential risk to the RPE that should be minimized by yet unknown cellular mechanisms.
The raising of defensive awareness among children and young people is one of the fundamental roles in the process of creating a defence system, and thus the national security of the Republic of Poland. It should start at the stage of upbringing in the family home and then evolve with the help of educational facilities and their accompanying institutions, among which the Armed Forces of the Republic of Poland should be mentioned in particular. It is important to note that care for the creation of a reliable security system rests not only with an institution such as the Armed Forces of the Republic of Poland and other uniformed services, but also with every citizen of the Polish state – in accordance with the law in force. Proper development of defensive awareness would not be possible if it were not for close cooperation between the Armed Forces of the Republic of Poland and the education sector. This is evidenced by the results of a pilot study, presented in the follow-ing article, conducted in the form of a questionnaire among eighth-grade students of the Henryk Sienkiewicz Primary School in Siedlce, as well as students of two third-grade classes with the military profile, at the European Secondary School of Uniformed Services in Wrocław. Their main objective was to show the degree of defence awareness formation among children and young people, using specific methods and institutions that have a direct impact on this process. As it was shown – as a result of the research analysis – a group of respondents, regardless of the knowledge they already have, want to continue to deepen it. This means that specific projects need to be created which in cooperation with many pro-defence organisations have a direct impact on shaping the security of the Polish state through working with its youngest citizens
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