Exploring a synthetic organoselenium compound for antioxidant pharmacotherapy--toxicity and effects on ROS-production.
The organoselenium antioxidant 1 was previously found to act as a catalytic antioxidant in a two-phase lipid peroxidation system. In aqueous environment, selenide 1 quenched ABTS-radicals more efficiently than Trolox and ascorbic acid. The selenide dose-dependently scavenged reactive oxygen and nitrogen species more efficiently than Trolox for neutrophils and PMA-stimulated macrophages, with 50% inhibitory concentrations in the low micromolar range. In addition no sign of toxicity or effect on cell viability was seen when culturing five human cell lines in concentrations up to 200 microM of selenide 1 for up to seven days. We therefore feel that the compound would be a good candidate for future drug development for prevention or treatment of disorders caused by or involving free radical-mediated or oxidative tissue damage.
Department of Biochemistry and Organic Chemistry, Uppsala University, PO Box 576, SE-751 23 Uppsala, Sweden.
Henrik
H
Johansson
Olov
O
Svartström
Prasad
P
Phadnis
Lars
L
Engman
Marjam Karlsson
MK
Ott
D002460:Cell Line; D002839:Chromans / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D016566:Organoselenium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism*
D002839:Chromans; D016166:Free Radical Scavengers; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid