1.Antioxidant Rescue of Selenomethionine-Induced Teratogenesis in Zebrafish Embryos.
Arnold MC1, Forte JE2, Osterberg JS2, Di Giulio RT2. Arch Environ Contam Toxicol. 2015 Oct 24. [Epub ahead of print]
Selenium (Se) is an essential micronutrient that can be found at toxic concentrations in surface waters contaminated by runoff from agriculture and coal mining. Zebrafish (Danio rerio) embryos were exposed to aqueous Se in the form of selenate, selenite, and L-selenomethionine (SeMet) in an attempt to determine if oxidative stress plays a role in selenium embryo toxicity. Selenate and selenite exposure did not induce embryo deformities (lordosis and craniofacial malformation). L-selenomethionine, however, induced significantly higher deformity rates at 100 µg/L compared with controls. SeMet exposure induced a dose-dependent increase in the catalytic subunit of glutamate-cysteine ligase (gclc) and reached an 11.7-fold increase at 100 µg/L. SeMet exposure also reduced concentrations of TGSH, RGSH, and the TGSH:GSSG ratio. Pretreatment with 100 µM N-acetylcysteine significantly reduced deformities in the zebrafish embryos secondarily treated with 400 µg/L SeMet from approximately 50-10 % as well as rescued all three of the significant glutathione level differences seen with SeMet alone.
2.Effects of selenomethionine on acute toxicities from concurrent chemoradiation for inoperable stage III non-small cell lung cancer.
Mix M1, Ramnath N1, Gomez J1, de Groot C1, Rajan S1, Dibaj S1, Tan W1, Rustum Y1, Jameson MB1, Singh AK1. World J Clin Oncol. 2015 Oct 10;6(5):156-65. doi: 10.5306/wjco.v6.i5.156.
AIM: To prospectively determine the safety and tolerability of oral L-selenomethionine (SLM) with concurrent chemoradiation (CCRT) for Stage III non-small cell lung cancer (NSCLC) and estimate if the incidence and/or severity of adverse events could be reduced by its use.
3.Exploration of a potential difluoromethyl-nucleoside substrate with the fluorinase enzyme.
Thompson S1, McMahon SA1, Naismith JH1, O'Hagan D2. Bioorg Chem. 2016 Feb;64:37-41. doi: 10.1016/j.bioorg.2015.11.003. Epub 2015 Nov 18.
The investigation of a difluoromethyl-bearing nucleoside with the fluorinase enzyme is described. 5',5'-Difluoro-5'-deoxyadenosine 7 (F2DA) was synthesised from adenosine, and found to bind to the fluorinase enzyme by isothermal titration calorimetry with similar affinity compared to 5'-fluoro-5'-deoxyadenosine 2 (FDA), the natural product of the enzymatic reaction. F2DA7 was found, however, not to undergo the enzyme catalysed reaction with l-selenomethionine, unlike FDA 2, which undergoes reaction with l-selenomethionine to generate Se-adenosylselenomethionine. A co-crystal structure of the fluorinase and F2DA7 and tartrate was solved to 1.8Å, and revealed that the difluoromethyl group bridges interactions known to be essential for activation of the single fluorine in FDA 2. An unusual hydrogen bonding interaction between the hydrogen of the difluoromethyl group and one of the hydroxyl oxygens of the tartrate ligand was also observed. The bridging interactions, coupled with the inherently stronger C-F bond in the difluoromethyl group, offers an explanation for why no reaction is observed.
4.A randomized controlled trial of vitamin E and selenium on rate of decline in lung function.
Cassano PA1,2, Guertin KA3,4, Kristal AR5,6, Ritchie KE7,8, Bertoia ML9,10, Arnold KB11, Crowley JJ12, Hartline J13, Goodman PJ14, Tangen CM15, Minasian LM16, Lippman SM17, Klein E18. Respir Res. 2015 Mar 11;16:35. doi: 10.1186/s12931-015-0195-5.
BACKGROUND: The intake of nutrients with antioxidant properties is hypothesized to augment antioxidant defenses, decrease oxidant damage to tissues, and attenuate age-related rate of decline in lung function. The objective was to determine whether long-term intervention with selenium and/or vitamin E supplements attenuates the annual rate of decline in lung function, particularly in cigarette smokers.