title: Antioxidants inhibit SAA formation and pro-inflammatory cytokine release in a human cell model of alkaptonuria.
abstract: OBJECTIVE
  Alkaptonuria (AKU) is an ultra-rare autosomal recessive disease that currently lacks an appropriate therapy. Recently we provided experimental evidence that AKU is a secondary serum amyloid A (SAA)-based amyloidosis. The aim of the present work was to evaluate the use of antioxidants to inhibit SAA amyloid and pro-inflammatory cytokine release in AKU.
  
  
  METHODS
  We adopted a human chondrocytic cell AKU model to evaluate the anti-amyloid capacity of a set of antioxidants that had previously been shown to counteract ochronosis in a serum AKU model. Amyloid presence was evaluated by Congo red staining. Homogentisic acid-induced SAA production and pro-inflammatory cytokine release (overexpressed in AKU patients) were evaluated by ELISA and multiplex systems, respectively. Lipid peroxidation was evaluated by means of a fluorescence-based assay.
  
  
  RESULTS
  Our AKU model allowed us to prove the efficacy of ascorbic acid combined with N-acetylcysteine, taurine, phytic acid and lipoic acid in significantly inhibiting SAA production, pro-inflammatory cytokine release and membrane lipid peroxidation.
  
  
  CONCLUSIONS
  All the tested antioxidant compounds were able to reduce the production of amyloid and may be the basis for establishing new therapies for AKU amyloidosis.
authors.affiliation: Dipartimento di Biotecnologie, Università degli Studi di Siena, Chimica e Farmacia, Siena, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Spreafico
authors.forename: Lia
authors.initials: L
authors.lastname: Millucci
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ghezzi
authors.forename: Michela
authors.initials: M
authors.lastname: Geminiani
authors.forename: Daniela
authors.initials: D
authors.lastname: Braconi
authors.forename: Loredana
authors.initials: L
authors.lastname: Amato
authors.forename: Federico
authors.initials: F
authors.lastname: Chellini
authors.forename: Bruno
authors.initials: B
authors.lastname: Frediani
authors.forename: Elena
authors.initials: E
authors.lastname: Moretti
authors.forename: Giulia
authors.initials: G
authors.lastname: Collodel
authors.forename: Giulia
authors.initials: G
authors.lastname: Bernardini
authors.forename: Annalisa
authors.initials: A
authors.lastname: Santucci
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000474:Alkaptonuria / Q000378:metabolism*; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002460:Cell Line; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D010833:Phytic Acid / Q000494:pharmacology; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D013654:Taurine / Q000494:pharmacology; D008063:Thioctic Acid / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D016207:Cytokines; D000685:Serum Amyloid A Protein; D013654:Taurine; D008063:Thioctic Acid; D010833:Phytic Acid; D001205:Ascorbic Acid; D000111:Acetylcysteine
keywords: N-acetylcysteine; ascorbic acid; chondrocyte; homogentisic acid; inflammation; lipid peroxidation; lipoic acid; phytic acid; serum amyloid A; taurine