RESUMEN
Apocynin (4'-hydroxy-3'-methoxyacetophenone) is the most commonly used NADPH oxidase (Nox) inhibitor. However, its application raises serious controversies, as the compound has been reported to reveal some prooxidative effects. The aim of this study was to elucidate apocynin action on glutathione, the main intracellular antioxidant, metabolism in kidneys of Zucker diabetic fatty (ZDF) rat, a well established model of diabetes type 2. Additionally, apocynin effects were compared with those of melatonin. The experiments were performed on five groups of animals: (1) untreated lean (?/+) ZDF rats, (2) ZDF ?/+ rats treated with apocynin (2 g/l) in drinking water, (3) untreated obese diabetic (fa/fa) ZDF rats, (4) ZDF fa/fa rats treated with apocynin (2 g/l) in drinking water, and (5) ZDF fa/fa rats treated with melatonin (20 mg/l) in drinking water. After 8weeks of the treatment, the following parameters were measured in kidneys: NADPH oxidase activity, the rate of hydroxyl free radicals (HFR) production, GSH and GSSG content and the activities of the enzymes of glutathione metabolism: γ-glutamylcysteine synthetase (GCS), glutathione reductase (GR) and glutathione peroxidase (GPx). Compared to ?/+ controls, ZDF fa/fa rats exhibited increased Nox activity, accelerated HFR generation and dramatically lowered GSH/GSSG ratio accompanied by increased GPx and diminished GCS activities. In case of diabetic animals, apocynin treatment resulted in attenuation of both Nox activity and HFR production, restoration of control GSH/GSSG ratio (due to both an increase in GSH and a decline in GSSG content), normalization of GPx activity and a slight increase in GCS activity. Similar observations were made upon melatonin application to ZDF fa/fa rats. Thus, it is concluded that, in the diabetic model studied, apocynin extends a beneficial effect on renal glutathione homeostasis. The mechanism of this phenomenon involves attenuation of glutathione peroxidase activity, which is overstimulated under conditions of oxidative stress accompanying diabetes.
Asunto(s)
Acetofenonas/farmacología , Acetofenonas/uso terapéutico , Diabetes Mellitus Experimental/tratamiento farmacológico , Melatonina/farmacología , Obesidad , Animales , Glucemia/análisis , Peso Corporal/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Glutatión/orina , Glutatión Peroxidasa/orina , Glutatión Reductasa/orina , Radical Hidroxilo/metabolismo , Masculino , Melatonina/uso terapéutico , NADPH Oxidasas/antagonistas & inhibidores , NADPH Oxidasas/metabolismo , Ratas , Ratas ZuckerRESUMEN
Selenium is an essential trace element which is part of the active site of seleno-dependent glutathione peroxidase and type 1 deiodinase. Therefore, it plays a key role in thyroid hormone metabolism. The present work was undertaken in order to evaluate selenium status in two Ivory Coast populations: the first with high (Glanlé) and the second with low (Abidjan) prevalence of iodine deficiency. Selenium, glutathione peroxidase, glutathione reductase, glutathione and diglutathione were determined in blood and/or urine. In plasma and erythrocytes, selenium and glutathione peroxidase were dramatically low in Glanlé. Compared to Abidjan, selenium, glutathione peroxidase, vitamin E and riboflavin status were decreased whereas diglutathione was increased in Glanlé. The results clearly demonstrate a selenium deficiency and suggest an oxidant stress in Glanlé. Causes and consequences of this selenium deficiency and oxidant stress remain to be determined.
Asunto(s)
Yodo/deficiencia , Selenio/deficiencia , Antropología Cultural , Côte d'Ivoire , Glutatión/sangre , Glutatión/orina , Glutatión Peroxidasa/sangre , Glutatión Peroxidasa/orina , Glutatión Reductasa/sangre , Glutatión Reductasa/orina , Humanos , Selenio/sangre , Selenio/orinaRESUMEN
Nutriture of thiamine, riboflavin and folacin was assessed by two tests: thiamine (109 subjects) by the TPP effect of erythrocyte transketolase activity and urinary excretion of thiamine (mug/g creatinine); riboflavin (81 subjects) by the activation coefficient of erythrocyte glutathione reductase and excretion of riboflavin in urine (mug/g creatinine); and folacin (91 subjects) by estimation of folacin in red blood cells and in serum (ng/ml). The following correlation coefficients (r) were obtained: transketolase activity vs thiamine excretion: -0.33; glutathione reductase vs riboflavin excretion: -33; and red blood cell folacin vs serum folacin: 0.77. When "deficient" and "low" values were defined as "not acceptable" and compared with "acceptable" values, sensitivity of thiamine excretion was 54%, of riboflavin excretion 33% and of serum folacin level 90%. The respective value of specificity were 75%, 83% and 37%. Sensitivity of thiamine excretion and of serum folacin level, respectively, increased when stricter criteria of insufficiency were applied and assessment of "deficiency" of these vitamins rather than of "non-acceptability" was attempted.