The organotellurium compound ammonium trichloro(dioxoethylene-0,0′) tellurate enhances neuronal survival and improves functional outcome in an ischemic stroke model in mice
Journal
Journal of Neurochemistry
Journal Volume
102
Journal Issue
4
Pages
1232-1241
Date Issued
2007
Author(s)
Abstract
Ammonium trichloro(dioxoethylene-0,0′) tellurate (AS101) is a non-toxic organotellurium compound with pleiotropic activities. It was recently shown to induce production of the neurotrophic factor glial cell line-derived neurotrophic factor and to rescue neuronal-like PC-12 cells from neurotrophic factor deprivation-induced apoptosis. In this study, we show that AS101 improves functional outcome and reduces brain damage in a mouse model of focal ischemic stroke. Both pre-stroke and post-stroke intraperitoneal treatments with AS101 reduced infarct size and edema and improved the neurological function of the animals. AS101 treatments reduced both apoptotic and inflammatory caspase activities, and also inhibited protein tyrosine nitration suggesting that AS101 suppresses oxidative stress. Studies of cultured neurons showed that AS101 confers protection against apoptosis induced by either glucose deprivation or the lipid peroxidation product 4-hydroxynonenal. Moreover, AS101 treatment reduced glutamate-induced intracellular calcium elevation, a major contributor to neuronal death in stroke. As AS101 has an excellent safety profile in humans, our pre-clinical data suggest a potential therapeutic benefit of AS101 in patients suffering from stroke and other neurodegenerative conditions. ? 2007 International Society for Neurochemistry.
SDGs
Other Subjects
4 hydroxynonenal; ammonium trichloro(dioxyethylene o,o')tellurate; calcium; caspase; glucose; organotellurium derivative; animal cell; animal experiment; animal model; animal tissue; apoptosis; article; brain damage; brain function; brain infarction size; calcium cell level; cell protection; cell survival; cerebrovascular accident; controlled study; drug effect; drug efficacy; drug safety; enzyme activity; inflammation; lipid peroxidation; male; mouse; nerve cell; nitration; nonhuman; oxidative stress; priority journal; Analysis of Variance; Animals; Animals, Newborn; Anoxia; Calcium; Caspases; Cell Survival; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Ethylenes; Glucose; Infarction, Middle Cerebral Artery; Male; Mice; Mice, Inbred C57BL; Neurons; Neuroprotective Agents; Rats; Time Factors; Animalia; Mus
Type
journal article