Diphenyl diselenide, a simple glutathione peroxidase mimetic, inhibits human LDL oxidation in vitro

Oxidative modification of low-density lipoprotein (LDL) represents an important factor in atherogenesis. In the present study, we have investigated the antioxidant capability of diphenyl diselenide (PhSe)2, a simple organoseleno compound, against copper (Cu2+) and peroxyl radical-induced human LDL oxidation in vitro. In initial studies using human serum, (PhSe)2 caused a dose-dependent inhibition of Cu2+-induced lipid peroxidation, which was correlated to thiol consumption. (PhSe)2 increased lipid peroxidation lag phase and decreased lipid peroxidation rate in isolated human LDL, evaluated by measuring both conjugated diene (CD) and thiobarbituric acid reactive substances (TBARS) levels. Consistent with these observations, (PhSe)2 showed a marked inhibitory effect on 2,2-azobis(2-amidinopropane dihydrochloride) (AAPH)-induced oxidation of LDL or parinaric acid (PnA) incorporated into LDL. (PhSe)2 also displayed a dose-dependent protective effect against Cu2+-induced lipid peroxidation in rat aortic slices. Interestingly, besides the antioxidant effects of (PhSe)2 toward the lipid moieties of LDL, which was related to its thiol-peroxidase activity, protein moieties from human isolated LDL were also protected against Cu2+-induced oxidation. The results presented herein are the first to show that (i) (PhSe)2 inhibits lipid peroxidation in human isolated LDL in vitro, (ii) this phenomenon is related to its thiol-peroxidase activity, and (iii) this chalcogen also prevents the oxidation of protein moieties of human LDL. Taken together, such data render (PhSe)2 a promising molecule for pharmacological studies with respect to the atherogenic process.http://www.sciencedirect.com/science/article/B6T12-4S21TS2-1/1/38250cf8bae4a4195ccd8905cf5c2a8

Educomunicação, Transformação Social e Desenvolvimento Sustentável

Esta publicação apresenta os principais trabalhos dos GTs do II Congresso Internacional de Comunicação e Educação nos temas Transformação social, com os artigos que abordam principalmente Educomunicação e/ou Mídia-Educação, no contexto de políticas de diversidade, inclusão e equidade; e, em Desenvolvimento Sustentável os artigos que abordam os avanços da relação comunicação/educação no contexto da educação ambiental e desenvolvimento sustentável

Isatin-3-N4 -benzilthiosemicarbazone, a non-toxic thiosemicarbazone derivative, protects and reactivates rat and human cholinesterases inhibited by methamidophos in vitro and in silico

Organophosphates (OPs), which are widely used as pesticides, are acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. The inactivation of AChE results in the accumulation of acetylcholine at cholinergic receptor sites, causing a cholinergic crisis that can lead to death. The classical treatment for OP poisoning is administration of oximes, but these compounds are ineffective in some cases. Here we determined whether the new compound isatin-3-N4-benzilthiosemicarbazone (IBTC), which in our previous study proved to be an antioxidant and antiatherogenic molecule, could protect and reactivate AChE and BChE. Toxicity of IBTC after subcutaneous injection in mice was measured using assays for oxidized diclorofluoresceine (DCF), thiobarbituric acid reactive substances (TBARS), non-protein thiol (NPSH) levels, and catalase (CAT), sodium potassium (Na+/K+) ATPase, delta-aminolevulinic acid dehydratase (ALA-D), and glutathione peroxidases (GPx) enzyme activities. The cytotoxicity was evaluated and the enzymatic activity of cholinesterase was measured in human blood samples. Molecular docking was used to predict the mechanism of IBTC interactions with the AChE active site. We found that IBTC did not increase the amount of DCF-RS or TBARS, did not reduce NPSH levels, and did not increase CAT, (Na+/K+) ATPase, ALA-D, or GPx activities. IBTC protected and reactivated both AChE and BChE activities. Molecular docking predicted that IBTC is positioned at the peripheral anionic site and in the acyl binding pocket of AChE and can interact with methamidophos, releasing the enzyme’s active site. Our results suggest that IBTC, besides being an antioxidant and a promising antiatherogenic agent, is a non-toxic molecule for methamidophos poisoning treatment