No abstract

Elevated MPO (myeloperoxidase) levels are associated with multiple human inflammatory pathologies. MPO catalyses the oxidation of Cl−, Br− and SCN− by H2O2 to generate the powerful oxidants hypochlorous acid (HOCl), hypobromous acid (HOBr) and hypothiocyanous acid (HOSCN) respectively. These species are antibacterial agents, but misplaced or excessive production is implicated in tissue damage at sites of inflammation. Unlike HOCl and HOBr, which react with multiple targets, HOSCN targets cysteine residues with considerable selectivity. In the light of this reactivity, we hypothesized that Sec (selenocysteine) residues should also be rapidly oxidized by HOSCN, as selenium atoms are better nucleophiles than sulfur. Such oxidation might inactivate critical Sec-containing cellular protective enzymes such as GPx (glutathione peroxidase) and TrxR (thioredoxin reductase). Stopped-flow kinetic studies indicate that seleno-compounds react rapidly with HOSCN with rate constants, k, in the range 2.8×103–5.8×106 M−1·s−1 (for selenomethionine and selenocystamine respectively). These values are ~6000-fold higher than the corresponding values for H2O2, and are also considerably larger than for the reaction of HOSCN with thiols (16-fold for cysteine and 80-fold for selenocystamine). Enzyme studies indicate that GPx and TrxR, but not glutathione reductase, are inactivated by HOSCN in a concentration-dependent manner; k for GPx has been determined as ~5×105 M−1·s−1. Decomposed HOSCN did not induce inactivation. These data indicate that selenocysteine residues are oxidized rapidly by HOSCN, with this resulting in the inhibition of the critical intracellular Sec-dependent protective enzymes GPx and TrxR.

No abstract

Bis[2-(dimethylamino)ethyl] diselenide was prepared by the reaction of Na 2 Se 2 with ClCH 2 CH 2 NMe 2 . 2-(Dimethylamino)ethaneselenolate complexes of palladium() of the type [PdCl(SeCH 2 CH 2 NMe 2) 2 ] 4 have been synthesized and characterized by elemental analysis, IR and NMR ( 1 H, 31 P, 77 Se) spectroscopy. The structures of orange 1 and of violet (λ max = 514 nm) 2c have been established by single crystal X-ray diffraction analyses. The trimer 1 contains a six-membered Pd 3 Se 3 ring in twist conformation. The thermal behaviour of three complexes, yielding Pd 17 Se 15 has been investigated.

3,3'-diselenodipropionic acid (DSePA), a derivative of selenocystine, has been synthesized and examined for antioxidant activity, glutathione peroxidase (GPx) activity, and cytotoxicity. The effect of DSePA on membrane lipid peroxidation, release of hemoglobin, and intracellular K+ ion as a consequence of erythrocyte (red blood cells or RBCs) oxidation by free radicals generated by 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH) were used to evaluate the antioxidant ability. Lipid peroxidation, hemolysis, and K+ ion loss in RBCs were assessed, respectively, by formation of thiobarbituric acid reactive substances (TBARS), absorbance of hemoglobin at 532 nm and flame photometry. The IC50 values for lipid peroxidation, hemolysis, and K+ ion leakage were 45+/-5, 20+/-2, and 75+/-8 microM, respectively. DSePA treatment prevented the depletion of glutathione (GSH) levels in RBCs from free-radical-induced stress. DSePA is a good peroxyl radical scavenger and the bimolecular rate constant for the reaction of DSePA with a model peroxyl radical, trichloromethyl peroxyl radical (CCl 3O2*), was determined to be 2.7x10(8) M(-1) s(-1) using a pulse radiolysis technique. DSePA shows GPx activity with higher substrate specificity towards peroxides than thiols. The cytotoxicity of DSePA was studied in lymphocytes and EL4 tumor cells and the results showed that DSePA is nontoxic to these cells at the concentrations employed. These results when compared with two well-known selenium compounds, sodium selenite and ebselen, indicated that DSePA, although it shows lesser GPx activity, has higher free radical scavenging ability and lesser toxicity.