The effect of alpha-lipoic acid supplementation on oxidative stress markers and antioxidative defense in patients with schizophrenia

U odnosu na opštu populaciju, oboleli od shizofrenije imaju kraći životni vek i povećani rizik za razvoj somatskih pratećih bolesti. Visoka prevalenca metaboličkog sindroma u shizofreniji predstavlja značajan faktor rizika za razvoj koronarne bolesti i dijabetes melitusa tip 2. Iako su odnosi između metaboličkog sindroma i shizofrenije kompleksni i još uvek nedovoljno proučeni, pretpostavlja se da oksidativni stres predstavlja mehanizam koji ima integrativnu ulogu kako u razvoju metaboličkog sindroma, tako i njegovih komplikacija. Zbog toga su ciljevi ovog istraživanja bili da se odrede parametri oksidativnog stresa i antioksidativne zaštite kod obolelih od shizofrenije i zdravih ispitanika, kao i da se ispita nivo oksidativnog stresa u odnosu na prisustvo metaboličkog sindroma kod obolelih od shizofrenije. Iako rezultati dosadašnjih istraživanja ukazuju na izmenjenu enzimsku antioksidativnu aktivnost, redukovani nivo neenzimskih antioksidanasa, kao i povećani stepen lipidne peroksidacije, ograničen je broj studija koje ukazuju na mogućnost modulacije oksidativno-stresnog statusa u shizofreniji primenom antioksidanasa. Suplementacija dijetarnim antioksidansima može pružiti značajnu podršku endogenom antioksidativnom zaštitnom sistemu u prevenciji oksidativnih oštećenja, kao i regulaciji redoks osetljivih signalnih puteva. Uzimajući u obzir činjenicu da se alfa-liponska kiselina smatra jednim od najsnažnijih antioksidanasa, njenu sposobnost da prolazi krvno-moždanu barijeru i povećava nivo endogenih antioksidanasa, posebno glutationa, koji predstavlja glavni endogeni antioksidans u centralnom nervnom sistemu, kao i potencijalne pozitivne metaboličke efekte, pretpostavljeno je da suplementacija alfa-liponskom može imati potencijalno povoljne efekte kao dodatak antipsihotičnoj terapiji kod klinički stabilnih pacijenata sa shizofrenijom. U istraživanju je učestvovalo ukupno 60 pacijenata sa shizofrenijom, oba pola, starosti od 18 do 60 godina, u stabilnoj fazi bolesti. Kontrolna grupa je obuhvatila 60 zdravih ispitanika, sličnih godina i pola. Ispitivanjem uticaja suplementacije alfa-liponskom kiselinom na parametre oksidativnog stresa i antioksidativne zaštite, obuhvaćena je grupa od 18 obolelih od shizofrenije, kao i grupa od 38 zdravih ispitanika...Patients with schizophrenia have a reduced life expectancy and increased rates of physical illness compared with the general population. Metabolic syndrome is highly prevalent in individuals with schizophrenia and conveys a significantly increases risk of type 2 diabetes and cardiovascular disease. Although it may not be the main cause, increasing evidence indicate that oxidative stress may play an integral role in the pathogenesis of metabolic syndrome, as well as the pathogenesis of metabolic syndrome-related conditions. In recent years there has been an increasing interest in the oxidative stress in the schizophrenia. However, up to now, there have been no studies investigating the association between oxidative stress status and metabolic syndrome in schizophrenia. Therefore, the objectives of this study were to determine the presence of metabolic syndrome and evaluate the oxidative stress status, as well as possible associations amongst them in schizophrenic patients. Recent years, increasing interest exists in using nonenzymatic antioxidants as adjunctive or supplements to prevent oxidative damage and to improve some of the psychopathology and treatment-related side effects of antipsychotic drugs. Alpha-lipoic acid is recognized as a powerful antioxidant. The ability of alpha-lipoic acid to cross the blood-brain barrier and increases levels of endogenous antioxidants, especially glutathione, who presents a major endogenous antioxidant in the brain, may have particular importance for schizophrenia. The study group consisted of 60 patients with schizophrenia and 60 sex- and age-matched healthy controls. Eighteen medicated patients with schizophrenia and 38 healthy subjects (control group) received daily supplements of alpha-lipoic acid (500 mg/day) for three months. Analysis of oxidative stress parameters showed significantly higher lipid peroxidation and higher plasma total antioxidant status in patients with schizophrenia than in the control group. In contrast, their PON1 activity was lower compared to control subjects. There were no significant differences between the patients and controls when plasma superoxide dismutase activity and serum prooxidant-antioxidant balance levels were compared..

Encapsulation of α-lipoic acid intochitosan and alginate/gelatin hydrogel microparticles and its in vitro antioxidant activity

Alpha-lipoic acidis an organosulphur compound well-known for its therapeutic potential and antioxidant properties. However, the effective use of α-lipoic acid depends on biological plasma half-life and its preserving stability, which could be improved by encapsulation. In this study, α-lipoic acid was incorporated into chitosan microparticles obtained by reverse emulsion crosslinking technique, as well as into microparticles of alginate/gelatin crosslinked with zinc ions. Encapsulation of α-lipoic acid in both cases was carried out by swelling of synthesized dried microparticles by their dipping in a solution of the active substance under strictly controlled conditions. Encapsulation efficiency of α-lipoic acid obtained in this study was up to 53.9 %. The structural interaction of α-lipoic acid with the carriers was revealed by Fourier transform infrared spectroscopy. In vitro released studies showed that controlled release of α-lipoic acid was achieved through its encapsulation into chitosan microparticles. The results of in vitro antioxidative activity assays of released α-lipoic acid indicated that antioxidant activity was preserved at a satisfactory level. These obtained results suggested that chitosan microparticles could be suitable for modeling the controlled release of α-lipoic acid. [Projekat Ministartsva nauke Republike Srbije, br. III 46010 i br. III46001