Efeito do Cádmio e do Seleno-Furanosídeo sobre a Atividade da Δ-Aminolevulinato Desidratase de Ovário In Vitro e Ex Vivo

Abstract

δ- aminolevulinate dehydratase (δ-ALA-D) is a metalloenzyme that requires zinc ions for maximum catalytic activity. Due to its sulphidrilic nature, δ-ALA-D is very sensitive to the presence of oxidizing agents being inhibited by heavy metals that have a high affinity for sulfhydryl groups such as cadmium (Cd). Cd is a heavy metal and a non-essential element used industrially. It is one of the most toxic pollutants distributed in the environment, since anthropogenic activities have increased its concentration in the atmosphere and become a contaminant of food and water. An important source of Cd in humans is through inhalation of cigarette smoke, because since it has a high bioavailability, is easily deposited in various tissues, especially the reproductive tract. Although this metal can cause serious damage to embryos and reproductive organs, the precise mechanisms relating to its toxicity remain uncertain . The objective of this work was to evaluate the effect of cadmium and seleno - furanoside on the activity of the enzyme δ-ALA-D ovary , in vitro and ex vivo. We observed that low concentrations of Cd inhibited cow ovary δ-ALA-D activity in vitro and the IC 50 value obtained was 19.17 μM. The Seleno-furanoside (10, 50, 100, 200, 400 and 1000 μM) did not reverse the Cd toxicity in bovine ovarian tissue in vitro. It was also shown possible mechanism by which Cd inhibits the enzyme activity of δ-ALA-D using dithiothreitol (DTT) and Zinc Chloride (ZnCl 2 ), where it was shown that DTT (3 mM) protected against enzyme activity inhibited by Cd while the ZnCl 2 (100μM) did not protect the inhibitory effect of the metal, suggesting that the inhibition of enzyme activity is related to the oxidation of thiol groups. In the ex vivo sturdy using Swiss (adult females), acute exposure to Cd (2.5 and 5 mg / kg intraperitoneally) caused a significant inhibition of δ-ALA-D ovarian (about 27% and 34% activity, respectively). Therapy with seleno-furanosídeo ex vivo (100 μmol /kg) was able to restore enzyme activity. Thus, it was demonstred for the first time that the activity of δ-ALA-D ovarian enzyme is inhibited by Cd both in vitro and ex vivo. In addition, therapy with seleno-furanoside was effective in restoring the enzyme activity inhibited by Cd exposure in mice ovary but was not effective in reversing the effect of metal in vitro. This study found a new marker of toxicity of Cd in ovarian tissue, as well as the beneficial effect of a new compound for treating metal effect after acute exposure of Cd.

Effect of Cadmium and Seleno-furanoside on the Δ-Aminolevulinate Dehydratase Activity In Vitro and Ex Vivo.