RESUMO
Antioxidatives are widely used and recommended in common clinical praxis, even though they may have negative impact on our health under some circumstances (i.e. N-acetylcysteine, vitamin E, risk of lung cancer etc.). Our aim was to evaluate the role of exogenous scavengers in prevention of induced oxidative stress in rodents. Male ICR mice were used and acute hypoglycaemia was induced with insulin. The mice were randomized into eight experimental groups, either pretreated by vitamin C or vitamin E or combinations with respective vehicles. Total malondialdehyde (MDA), superoxide dismutase (SOD), and selenium-dependent glutathione peroxidase (GSHPx) activity were measured in brain tissue samples. ANOVA with a post-hoc Duncan or Turkey׳s tests were used for statistical evaluation. A statistically significant increase in brain MDA was observed after insulin-induced severe hypoglycaemia relative to normoglycaemia. Animals pretreated with vitamins, both in monotherapy and in combination (both P<0.05), had significantly lower MDA values compared with animals without pretreatment. Importantly, significant differences were also observed after combination of vitamin C and E in GSHPx and SOD (both P<0.05).
Assuntos
Ácido Ascórbico/uso terapêutico , Hipoglicemia/tratamento farmacológico , Vitamina E/uso terapêutico , Animais , Ácido Ascórbico/farmacologia , Glicemia/análise , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Suplementos Nutricionais , Quimioterapia Combinada , Glutationa Peroxidase/metabolismo , Hipoglicemia/sangue , Hipoglicemia/induzido quimicamente , Hipoglicemia/metabolismo , Insulina , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos ICR , Superóxido Dismutase/metabolismo , Vitamina E/farmacologiaRESUMO
Today, World Wide Web technology provides many opportunities in the disclosure of electronic learning and teaching content. The MEFANET project (MEdical FAculties NETwork) has initiated international, effective and open cooperation among all Czech and Slovak medical faculties in the medical education fields. This paper introduces the original MEFANET educational web portal platform. Its main aim is to present the unique collaborative environment, which combines the sharing of electronic educational resources with the use tools for their quality evaluation. It is in fact a complex e-publishing system, which consists of ten standalone portal instances and one central gateway. The fundamental principles of the developed system and used technologies are reported here, as well as procedures of a new multidimensional quality assessment.
Assuntos
Educação Médica/organização & administração , Internet , Segurança Computacional , Comportamento Cooperativo , República Tcheca , Educação Médica/métodos , Educação Médica/normas , EslováquiaRESUMO
Apocynin is a naturally occurring methoxy-substituted catechol, experimentally used as an inhibitor of NADPH oxidase. Since it acts as a potent inhibitor in studies with neutrophils and macrophages, no inhibitory effect can often be found in non-phagocyte cells. In our experiments, apocynin even stimulated reactive oxygen species (ROS) production by vascular fibroblasts. Even when added to macrophages, apocynin initially caused an increase in ROS production. The inhibition of ROS formation followed, suggesting that in the presence of leukocyte myeloperoxidase and hydrogen peroxide, apocynin is converted to another compound. Apocynin pre-activated with H2O2 and horseradish peroxidase (HRP) inhibited ROS production immediately. In non-phagocytes, apocynin stimulated ROS production and no inhibition was observed even after 60 min. Apocynin treated with H2O2 and HRP, however, decreased ROS production in the same manner as in macrophages. The stimulatory effect on ROS production can be abolished by tiron and superoxide dismutase (SOD), suggesting that superoxide was the produced species. The effect of apocynin was inhibited by diphenylene iodinium (DPI), a non-scavenging NADPH oxidase inhibitor. It can be summarized that apocynin stimulates cell superoxide production. In the presence of peroxidase and hydrogen peroxide, however, it is converted into another compound that acts as an inhibitor of superoxide production. It strongly suggests that under conditions in vivo, apocynin can have opposite effects on phagocytes and non-phagocyte cells. It acts as an inhibitor of phagocyte NADPH oxidase but also as a ROS production stimulator in non-phagocyte cells.
Assuntos
Acetofenonas/farmacologia , Antioxidantes/farmacologia , NADPH Oxidases/antagonistas & inibidores , Fagócitos/enzimologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Células Cultivadas , Inibidores Enzimáticos/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Masculino , Ratos , Ratos WistarRESUMO
The activities of superoxide dismutase, glutathione peroxidase (GPX) and catalase--the enzymatic scavengers of reactive oxygen species and the activities of xanthine oxidoreductase and xanthine oxidase, an enzyme known to generate reactive oxygen species, were studied in the corneas of normal rabbit eyes of various ages (1 month--young eyes; 4-9.5 months--young adult eyes; 2.0-2.75 years--middle aged eyes; 3.0-5.0 years--aged eyes). The activities of GPX, superoxide dismutase, xanthine oxidoreductase and xanthine oxidase were investigated biochemically in the scraped corneal epithelium. Catalase activity was detected histochemically in the corneal epithelium and endothelium. The results show that young corneas revealed lower activities of all the antioxidant enzymes investigated than did young adult corneas, in which enzymatic activities reached their maximum. In middle-aged corneas, GPX and catalase activities remained approximately at the same levels as seen in young adult corneas, whereas superoxide dismutase activity was decreased. In aged corneas, the activities of all antioxidant enzymes were dramatically decreased or even lost (catalase activity in the corneal endothelium). In contrast, xanthine oxidoreductase activity only slightly decreased with age and the xanthine oxidase proportion of total xanthine oxidoreductase remained unchanged. GPX, superoxide dismutase and catalase are important antioxidant enzymes protecting the cornea against the oxidative damage. Because the activities of these enzymes are lower in young animals and greatly reduced in aged animals, it is suggested that young and particularly aged corneas might be more susceptible to oxidative stress than are young adult corneas. This presumption is supported by the fact that the activities of prooxidant enzymes (xanthine oxidoreductase/xanthine oxidase) are only slightly decreased in aged corneas as compared to young adult corneas so that some imbalance between antioxidant and prooxidant enzymes exists already in the normal aged corneas.
Assuntos
Envelhecimento/metabolismo , Córnea/enzimologia , Animais , Catalase/metabolismo , Epitélio Corneano/enzimologia , Feminino , Glutationa Peroxidase/metabolismo , Estresse Oxidativo/fisiologia , Oxirredutases/metabolismo , Coelhos , Superóxido Dismutase/metabolismo , Xantina Oxidase/metabolismoRESUMO
BACKGROUND: The increased permeability of the glomerular capillary wall in adriamycin nephropathy may be mediated by increased generation of free radicals, possibly also by the non-enzymatic production of isoprostanes induced by oxidative stress. ACE inhibitors and angiotensin II antagonists may reduce proteinuria, perhaps by decreasing intraglomerular pressure and increasing the selective permeabiity of the glomerular capillary wall. MATERIAL/METHODS: We compared the effect of an ACE inhibitor, enalapril, and an angiotensin II antagonist, losartan, on total malodialdehyde in blood and the urinary excretion of certain eicosanoids and their metabolites (TxB(2), 6-keto-PGF(1alpha), bicyclo-PGE(2) and 8-isoprostane) in experimental adriamycin-induced nephrotic syndrome in rats. RESULTS: Increased proteinuria in adriamycin-treated rats was not prevented by losartan, but tended to be partly mitigated by enalapril. However, both losartan and enalapril prevented the adriamycin-induced increase of total MDA in serum, but urinary excretion of 8-isoprostane was increased in nephrotic rats treated by losartan compared to controls. The enalapril-induced increase in urinary excretion of bicyclo-PGE(2) was possibly mediated by kinins. Proteinuria positively correlated with urinary excretion of 8-isoprostane, and proteinuric rats also had a significantly higher urinary excretion of 8-isoprostane than non-proteinuric rats. CONCLUSIONS: Proteinuria in the acute phase of adriamycine nephropathy may be dependent on free radical generation and the formation of 8-isoprostane. The mild antiproteinuric effect of enalapril, but not losartan, may suggest the contributory role of the inhibition of kinin degradation in the antiproteinuric action of enalapril in this model of nephrotic syndrome.