Metal sulfate-mediated induction of pathogenic genes and repression by phenyl butyl nitrone and Feralex-G

Neuroreport
Theodore P A KruckW J Lukiw

Abstract

Neurotoxic metal-induced oxidative damage to nervous tissue has been implicated in several progressive neurodegenerative disorders including Alzheimer's disease. In this study, using human brain cells in primary culture, the quenching of metal sulfate-induced reactive oxygen species (ROS) and ROS-sensitive gene expression was studied using the antioxidants ascorbate, folic acid, phenyl butyl nitrone and the chelators desferrioxamine and Feralex-G. Antioxidants ascorbate, folic acid, phenyl butyl nitrone, desferrioxamine or Feralex-G were found to quench ROS and cPLA2 and COX-2 gene induction to various degrees, and a synergism was observed when certain combinations of them were used. These findings support the idea that specific antioxidants and metal ion chelators when used together can effectively and synergistically quench ROS-mediated induction of pathogenic gene expression.

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Citations

Jan 19, 2010·Journal of Medicinal Chemistry·Hongxia JinPeter F Kador
Oct 21, 2011·Advances in Pharmacological Sciences·Satoru OshiroMasataka Kikuchi
Jun 10, 2008·Expert Opinion on Emerging Drugs·Walter J Lukiw
Nov 22, 2011·Journal of Inorganic Biochemistry·Maire E PercyWalter J Lukiw
Jan 30, 2009·Medicinal Research Reviews·Silvia BologninPaolo Zatta
May 2, 2014·Frontiers in Aging Neuroscience·Surjyadipta BhattacharjeeWalter J Lukiw
May 7, 2009·Current Opinion in Neurology

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