Ações biológicas de compostos de selênio e telúrio: efeitos tóxicos sobre o sistema nervoso central

The biochemistry and pharmacology of selenium is a subject of intense current interest, particularly from the viewpoint of public health. Selenium, long recognized as a dietary oxidant, is now known to be an essential component of the active sites of several enzymes. In contrast to the case of selenium, surprisingly little is known of the occurrence of tellurium in biological systems. However, tellurium shares chemical characteristics with selenium. Taking into account, researches that focus on biological activities of selenium and tellurium are the greatest interest. These compounds are important intermediates in organic synthesis and present some pharmacological properties. Besides, selenium and tellurium can oxidize SH groups of proteins since they could be toxic to animais. Based in this property, some studies revealed that selenium and tellurium are potentially neurotoxic. In this way, this review point out toxic effects induced by selenium and tellurium organic compounds highlight the effects on central nervous system.A bioquímica e a farmacologia do selênio tem sido assunto de muito interesse, particularmente sob o ponto de vista de saúde pública. O selênio há muito tempo descrito como um antioxidante, e agora também conhecido por ser um componente essencial do sítio ativo de diversas enzimas. Ao contrário do selênio, pouco é conhecido sobre a ocorrência de telúrio em sistemas biológicos. Apesar de não apresentar função fisiológica descrita, o telúrio compartilha algumas peculiaridades químicas com o selênio. Neste contexto, pesquisas que revelam as ações biológicas de moléculas que contenham átomos de selênio e telúrio mostram-se de grande importância em virtude de suas aplicações como ferramentas sintéticas em química orgânica e de suas propriedades farmacológicas. Paralelo a isso, já se sabe que moléculas que contenham selênio e telúrio são capazes de reagir com grupos SH de proteínas biologicamente ativas. Com base nesta característica, estudos revelam que estes compostos são potencialmente tóxicos ao sistema nervoso central (SNC). Sendo assim, esta revisão aborda os efeitos tóxicos induzidos por compostos orgânicos de selênio e telúrio, com ênfase nos efeitos sobre o SNC

Uric Acid Reacts with Peroxidasin, Decreases Collagen IV Crosslink, Impairs Human Endothelial Cell Migration and Adhesion

Uric acid is considered the main substrate for peroxidases in plasma. The oxidation of uric acid by human peroxidases generates urate free radical and urate hydroperoxide, which might affect endothelial function and explain, at least in part, the harmful effects of uric acid on the vascular system. Peroxidasin (PXDN), the most recent heme-peroxidase described in humans, catalyzes the formation of hypobromous acid, which mediates collagen IV crosslinks in the extracellular matrix. This enzyme has gained increasing scientific interest since it is associated with cardiovascular disease, cancer, and renal fibrosis. The main objective here was to investigate whether uric acid would react with PXDN and compromise the function of the enzyme in human endothelial cells. Urate decreased Amplex Red oxidation and brominating activity in the extracellular matrix (ECM) from HEK293/PXDN overexpressing cells and in the secretome of HUVECs. Parallelly, urate was oxidized to 5-hydroxyisourate. It also decreased collagen IV crosslink in isolated ECM from PFHR9 cells. Urate, the PXDN inhibitor phloroglucinol, and the PXDN knockdown impaired migration and adhesion of HUVECs. These results demonstrated that uric acid can affect extracellular matrix formation by competing for PXDN. The oxidation of uric acid by PXDN is likely a relevant mechanism in the endothelial dysfunction related to this metabolite