title: R- and S-equol have equivalent cytoprotective effects in Friedreich's ataxia.
abstract: BACKGROUND
  Estradiol (E2) is a very potent cytoprotectant against a wide variety of cellular insults in numerous different cell models, including a Friedreich's ataxia (FRDA) model. Previously, we demonstrated that estrogen-like compounds are able to prevent cell death in an FRDA model independent of any known estrogen receptor (ER) by reducing reactive oxygen species (ROS) and the detrimental downstream effects of ROS buildup including oxidative damage to proteins and lipids and impaired mitochondrial function.
  
  
  RESULTS
  We have previously demonstrated by western blot that our cell model lacks ERα and expresses only very low levels of ERβ. 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 ERβ agonist S-equol and its ERα-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute for Aging and Alzheimer's Disease Research, Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Richardson
authors.forename: James W
authors.initials: JW
authors.lastname: Simpkins
mesh_terms: D000328:Adult; D019328:Buthionine Sulfoximine; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection; D060754:Equol / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005621:Friedreich Ataxia; D006801:Humans; D018384:Oxidative Stress; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004967:Estrogens; D020011:Protective Agents; D017382:Reactive Oxygen Species; D004958:Estradiol; D019328:Buthionine Sulfoximine; D060754:Equol