tellurium and ebselen

Peroxynitrite is an oxidant generated under inflammatory conditions, acting in defense against invading microorganisms. There is a need for protection of the organism from damage inflicted by peroxynitrite. Selenium-containing compounds, notably ebselen, have a high second-order reaction rate constant (approx. 2 x 10(6) M(-1) s(-1)), which makes them candidates for efficient protection. This applies also for selenium in proteins, occurring as selenocysteine or selenomethionine residues. Glutathione peroxidases, thioredoxin reductase, and selenoprotein P have been shown to play a potential role in protection against peroxynitrite. Tellurium-containing compounds also react with peroxynitrite.

Topics: Antioxidants; Azoles; Free Radicals; Glutathione Peroxidase; Humans; Isoindoles; Nitrates; Organoselenium Compounds; Oxidants; Oxidative Stress; Proteins; Selenocysteine; Selenomethionine; Selenoprotein P; Selenoproteins; Tellurium; Thioredoxin-Disulfide Reductase

In this study, we evaluated the effects of three simple organochalcogenides (diphenyl diselenide, diphenyl ditelluride and diphenyl telluride) and ebselen on the glutamate-driven 45Ca2+ influx into chick embryonic retinal cells, as well as their effects on the excitotoxic injury in retina cells. None of the compounds tested interfered with basal 45Ca2+ uptake. Diphenyl diselenide and diphenyl ditelluride had no effects on glutamate-driven 45Ca2+ influx. Diphenyl telluride (100-400 microM) decreased and ebselen (100-400 microM) completely blocked the glutamate-driven 45Ca2+ influx (P < 0.01) into chick retinal explants. The assessment of neural injury was made spectrophotometrically by quantification of cellularly reduced MTT (3(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide) 24 h after the beginning of glutamate exposure (8 h). Ebselen had no effects on retinal MTT reduction when co-incubated with glutamate for 8 h. However, when ebselen (100 and 400 microM) was co-incubated for 8 h with glutamate and remained in the incubation media until MTT evaluation (24 h after the beginning of incubation), it protected retinal cells against the decrease in MTT reduction induced by glutamate. These data indicate that besides its capacity of interacting with Ca2+ channels, other mechanisms are involved in the neuroprotection afforded by ebselen in this work, possibly its antioxidant properties.

Topics: Animals; Azoles; Benzene Derivatives; Calcium; Calcium Channels; Chalcogens; Chick Embryo; Dose-Response Relationship, Drug; Glutamic Acid; Isoindoles; Nerve Degeneration; Neurons; Neuroprotective Agents; Neurotoxins; Organometallic Compounds; Organoselenium Compounds; Retina; Tellurium; Tetrazolium Salts; Thiazoles

The predominance of oxidative stress in many tumour cell environments provides a means to selectively target these cells via protein oxidation. The zinc fingers of transcription factors utilise cysteine thiols for structural zinc coordination. Redox control of DNA binding regulates transcription and therefore the overall rates of proliferation, apoptosis and necrosis in the carcinoma. We report here the adverse effects of glutathione peroxidase (GPx) mimics towards zinc finger motifs and PC12 cell survival. Nanomolar catalyst concentrations facilitated H2O2-induced oxidation of an Sp1 transcription factor fragment. In PC12 cells GPx catalysis triggered a significant increase in cell death, correlating with severity of oxidative stress. As a consequence, we conclude that GPx mimics are potential chemotherapeutic agents.

Topics: Animals; Antioxidants; Azoles; Catalysis; Cell Survival; Chalcogens; Dose-Response Relationship, Drug; Drug Synergism; Glutathione Peroxidase; Hydrogen Peroxide; Isoindoles; Organometallic Compounds; Organoselenium Compounds; Oxidation-Reduction; Oxidative Stress; PC12 Cells; Peptide Fragments; Rats; Reactive Oxygen Species; Selenium; Sp1 Transcription Factor; Tellurium; Zinc Fingers

Previous literature reports have demonstrated that nucleated trout erythrocytes in conditions of oxidative stress are subjected to DNA and membrane damage, and inactivation of glutathione peroxidase. The present study was undertaken to evaluate the ability of three diaryl tellurides and the organoselenium compound ebselen to protect trout (Salmo irideus) erythrocytes against oxidative stress, induced thermally and by a variation of pH. The antioxidant ability of these molecules was evaluated through chemiluminescence. Impairment of DNA was assessed using the comet assay, a rapid and sensitive single cell gel electrophoresis technique, used to detect primary DNA damage in individual cells. At low concentrations (<10 microM), all the compounds used presented a protective effect on DNA damage without altering the hemolysis rate. In higher concentrations, they accelerated the hemolysis rate and two of the diaryl tellurides were strongly genotoxic.

Topics: Animals; Antioxidants; Azoles; Comet Assay; DNA Damage; Dose-Response Relationship, Drug; Erythrocytes; Hemolysis; Hot Temperature; Hydrogen-Ion Concentration; Isoindoles; Luminescent Measurements; Mutagenicity Tests; Oncorhynchus mykiss; Organometallic Compounds; Organoselenium Compounds; Oxidative Stress; Tellurium