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1.
Mol Cell Biochem ; 320(1-2): 141-8, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18839280

RESUMO

The aim of our work was to study (1) the antioxidant properties of lipoic acid (LA) and its reduced metabolite dihydrolipoic acid (DHLA) formed by reduction of LA and (2) the effects of treatment with LA and DHLA on (a) K(+) efflux from human red blood cells and (b) post-ischemic recovery and oxidative stress in isolated perfused rat hearts challenged with an ischemia-reperfusion (IR) sequence. In vitro, we used xanthine and xanthine oxidase to generate superoxide anion, which is not directly measurable by electron paramagnetic resonance (EPR), but specifically oxidizes the spin probe CPH into an EPR-detectable long lasting CP(*) nitroxide radical. While 5 mM of LA was ineffective in reducing the kinetics of CP(*) nitroxide formation, DHLA was shown to lessen this rate in a dose-dependent manner and at 30 mM was even more efficient than 300 UI/ml SOD. These results are in agreement with the fact that DHLA is able to directly scavenge superoxide anion. Red cells are a good model to investigate oxidative damage in biological membranes; hence, we used a suspension of erythrocytes incubated with 2,2(')-azobis(2-amidinopropane) hydrochloride (AAPH) which generates in vitro free radicals. DHLA provided more effective protection of red cells membranes than LA; DHLA was comparable to Trolox for its antioxidant potency. In vivo, treatment of rats (50 mg/kg/day i.p. for 7 days) with LA induced a slight increase in coronary flow (CF) in isolated perfused hearts, after 30 min of global total ischemia. This effect was not associated with an improvement in contractile function and reduction of myocardial oxidative stress. In conclusion, because of their ability to scavenge free radicals, LA and to an even greater degree DHLA were able to protect the membranes of red blood cells. This finding suggests that LA and DHLA might be useful in the treatment of diseases associated with oxidative stress such as diabetes.


Assuntos
Antioxidantes/farmacologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Coração , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Ácido Tióctico/análogos & derivados , Ácido Tióctico/farmacologia , Adaptação Fisiológica/efeitos dos fármacos , Animais , Cromanos/farmacologia , Eritrócitos/citologia , Eritrócitos/metabolismo , Coração/efeitos dos fármacos , Coração/fisiopatologia , Humanos , Masculino , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/metabolismo , Potássio/metabolismo , Ratos , Ratos Wistar , Superóxidos/metabolismo
2.
Ann Cardiol Angeiol (Paris) ; 57(3): 161-5, 2008 Jun.
Artigo em Francês | MEDLINE | ID: mdl-18571145

RESUMO

Alpha-Lipoic acid (ALA) is a natural compound, chemically named 1,2-dithiolane-3-pentanoic acid, also referred to as thioctic acid. In humans, ALA is synthetized by the liver and other tissues with high metabolic activity: heart, kidney. ALA is both water and fat soluble and therefore, is widely distributed in both cellular membranes and cytosol. Recently, a greater deal of attention has been given to antioxidant function for ALA and its reduced formed: dihydrolipoic acid (DHLA). ALA scavenges hydroxyl radicals, hypochlorous acid and singlet oxygen. It may also exert antioxidant effects in biological systems through transitional metal chelation. Dihydrolipoic acid has been shown to have antioxidant but also pro-oxidant properties in systems in which hydroxyl radical was generated. ALA/DHLA ratio has the capacity to recycle endogenous antioxidants such as vitamin E. A number of experimental as well as clinical studies point to the usefulness of ALA as a therapeutic agent for such diverse conditions as diabetes, atherosclerosis, insulin resistance, neuropathy, neurodegenerative diseases and ischemia-reperfusion injury. ALA represents a potential agent on the vascular endothelium, recording to ALA/DHLA redox couple is one of the most powerful biological antioxidant systems.


Assuntos
Antioxidantes/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Ácido Tióctico/uso terapêutico , Tolueno/análogos & derivados , Complexo Vitamínico B/uso terapêutico , Ácido 8,11,14-Eicosatrienoico , Experimentação Animal , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Diabetes Mellitus/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Sequestradores de Radicais Livres , Humanos , Radical Hidroxila , Resistência à Insulina , Doenças Neurodegenerativas/tratamento farmacológico , Oxirredução , Ensaios Clínicos Controlados Aleatórios como Assunto , Ratos , Ácido Tióctico/metabolismo , Ácido Tióctico/farmacologia , Complexo Vitamínico B/metabolismo , Complexo Vitamínico B/farmacologia
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