Oksidativni stres

The unceasing need for oxygen is in contradiction to the fact that it is in fact toxic to mammals. Namely, its monovalent reduction can have as a consequence the production of short-living, chemically very active free radicals and certain non-radical agents (nitrogen-oxide, superoxide-anion-radicals, hydroxyl radicals, peroxyl radicals, singlet oxygen, peroxynitrite, hydrogen peroxide, hypochlorous acid, and others). There is no doubt that they have numerous positive roles, but when their production is stepped up to such an extent that the organism cannot eliminate them with its antioxidants (superoxide-dismutase, glutathione-peroxidase, catalase, transferrin, ceruloplasmin, reduced glutathion, and others), a series of disorders is developed that are jointly called 'oxidative stress.' The reactive oxygen species which characterize oxidative stress are capable of attacking all main classes of biological macromolecules, actually proteins, DNA and RNA molecules, and in particular lipids. The free radicals influence lipid peroxidation in cellular membranes, oxidative damage to DNA and RNA molecules, the development of genetic mutations, fragmentation, and the altered function of various protein molecules. All of this results in the following consequences: disrupted permeability of cellular membranes, disrupted cellular signalization and ion homeostasis, reduced or loss of function of damaged proteins, and similar. That is why the free radicals that are released during oxidative stress are considered pathogenic agents of numerous diseases and ageing. The type of damage that will occur, and when it will take place, depends on the nature of the free radicals, their site of action and their source. Neprekidna potreba za kiseonikom je kontradiktorna sa činjenicom da je on toksičan po sisare. Naime, njegova jednovalentna redukcija može imati za posledicu proizvodnju kratkoživećih, hemijski vrlo aktivnih, slobodnih radikala i nekih neradikalskih agenasa (azot-oksida, superoksid anjon-radikala, hidroksilnog radikala, peroksilnog radikala, singletnog kiseonika, peroksinitrita, vodonik-peroksida, hipohloraste kiseline i dr.). Neosporno je da oni imaju brojne poželjne uloge, ali kada im se proizvodnja pojača toliko da organizam ne može svojim antioksidansima (superoksid dismutaza, glutation peroksidaza, katalaza, transferin, ceruloplazmin, redukovani glutation i sl.) da ih ukloni, razvija se serija poremećaja koji se jednim imenom nazivaju 'oksidativni stres'. Reaktivne kiseonične vrste koje karakterišu oksidativni stres su sposobne da napadnu sve glavne klase bioloških makromolekula, odnosno proteine, DNK i RNK molekule, a naročito lipide. Pod uticajem slobodnih radikala dolazi do peroksidacije lipida ćelijskih membrana, oksidativnih oštećenja DNK i RNK molekula, razvoja genetskih mutacija, fragmentacije i promene funkcije najrazličitijih proteinskih molekula. Sve to ima za posledicu: narušavanje propustljivosti ćelijskih membrana, poremećaja ćelijske signalizacije i homeostaze jona, smanjenja ili gubitka funkcija oštećenih proteina i sl. Zato se slobodni radikali, koji se oslobađaju tokom oksidativnog stresa, smatraju patogenim agensima mnogih bolesti i starenja. Koja vrsta oštećenja će se desiti i kada, zavisi od prirode slobodnih radikala, mesta delovanja i njihovog izvora.