%0 Journal Article
%T R- and S-Equol have equivalent cytoprotective effects in Friedreich¡¯s Ataxia
%A Timothy E Richardson
%A James W Simpkins
%J BMC Pharmacology and Toxicology
%D 2012
%I BioMed Central
%R 10.1186/2050-6511-13-12
%X We have previously demonstrated by western blot that our cell model lacks ER¦Á and expresses only very low levels of ER¦Â. Using L-buthionine (S,R)-sulfoximine (BSO) to induce oxidative stress in human FRDA fibroblasts, we determine the potency and efficacy of the soy-derived ER¦Â agonist S-equol and its ER¦Á-preferring enantiomer, R-equol in vitro on cell viability and ROS accumulation. Here we demonstrate that these equol biphenolic compounds, while significantly less potent and efficacious than E2, provide statistically similar attenuation of ROS and cytoprotection against a BSO-induced oxidative insult.These preliminary data demonstrate that estrogen and soy-derived equols could have a beneficial effect in delaying the onset and decreasing the severity of symptoms in FRDA patients by an antioxidant mechanism. In addition, these data confirm that the protection seen previously with E2 was indeed unrelated to ER binding.First recognized in 1863 [1], Friedreich¡¯s Ataxia (FRDA) is the most common hereditary form of ataxia characterized by an autosomal recessive GAA trinucleotide repeat in the FXN gene, resulting in the absence of frataxin protein [2,3]. The exact function of frataxin is unclear, however it is necessary for iron metabolism within cells, Fe-S cluster assembly in proteins, and maintenance of cellular redox state. Without sufficient levels of frataxin, reactive oxygen species (ROS) begin to accumulate and cells are unable to maintain function of Fe-S cluster proteins essential for mitochondrial respiration leading to mitochondrial dysfunction, insufficient energy production and ultimately cell death, beginning in organs with greater energy requirements and thus more dependent on aerobic ATP production, such as the heart, brain and spinal cord. Symptoms usually begin in the second decade of life and include ataxia, neural hearing and ocular abnormalities, scoliosis, diabetes and cardiomyopathy, which is the most common cause of premature death in FRDA patien
%K Equol
%K 17¦Â-estradiol
%K Antioxidants
%K Friedreich¡¯s Ataxia
%K Fibroblasts
%K Neuroprotection
%U http://www.biomedcentral.com/2050-6511/13/12