title: Effect of oral genistein administration in early and late phases of allergic encephalomyelitis.
abstract: OBJECTIVE
  Experimental allergic encephalomyelitis (EAE) is an autoimmune disease validated as animal model of multiple sclerosis (MS). Administration of genistein, a phytoestrogenic component of soy, to mice at the onset of EAE is known to attenuate the clinical signs of the disease. The potential effects of genistein on established EAE is less studied. In the current study, we aimed to compare the effects of genistein administration on EAE severity in early and late phases of the disease.
  
  
  METHODS
  The C57BL/6 mice were induced with EAE, using MOG 35-55 and gavaged with genistein (300 mg/kg) either after the appearance of the first clinical sign or 30 days post disease induction for ten days. 24 hr after the last gavage, mice were sacrificed. Brains and spleens were removed for assessing lymphocyte proliferation, cell cytotoxicity, and cytokine profile. Spinal cords were dissected to assess the amount of demyelination using Luxol fast blue/cresyl violet staining.
  
  
  RESULTS
  Administering mice with genistein, after the establishment of EAE, did not reverse the clinical signs of disease. However, treating with genistein at the onset of disease alleviated the clinical signs by reducing neuronal demyelination. Genistein suppressed the production of IFN-γ and enhanced IL-10 secretion in splenocyte and brain. Genistein also reduced IL-12 and TNF-α secretion in splenocytes, suppressed the proliferation of T-cells, and reduced the cell cytotoxicity.
  
  
  CONCLUSIONS
  Genistein oral therapy might only reduce EAE severity if started in early phases of the disease.
authors.affiliation: Multiple Sclerosis Research Center-Neuroscience Institute, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran ; Shefa Neuroscience Research Center, Tehran, Iran.
authors.forename: Soodeh Razeghi
authors.initials: SR
authors.lastname: Jahromi
authors.affiliation: Department of Nutrition and Health, Tabriz University of Medical Sciences.
authors.forename: Seyed Rafi
authors.initials: SR
authors.lastname: Arrefhosseini
authors.affiliation: Department of Virology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran ; Shefa Neuroscience Research Center, Tehran, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Ghaemi
authors.affiliation: Department of Tissue Engineering , Faculty of Advanced Medicine and Technology, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Akram
authors.initials: A
authors.lastname: Alizadeh
authors.affiliation: DVM, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad , Iran.
authors.forename: Fateme
authors.initials: F
authors.lastname: Sabetghadam
authors.affiliation: Department of Neurology, Iranian Center of Neurological Research-Neuroscience Institute, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Togha
keywords: Experimental allergic; Genistein; Immunomodulation; Interferon-gamma; Multiple sclerosis; encephalomyelitis (EAE)