title: Evaluation of anti-oxidant treatments in an in vitro model of alkaptonuric ochronosis.
abstract: OBJECTIVE
  Alkaptonuria (AKU) is a rare genetic disease associated with deficient homogentisate 1,2-dioxygenase activity in the liver. This leads to the accumulation of homogentisic acid (HGA) and its oxidized/polymerized products in connective tissues, which in turn become characterized by the presence of melanin-like pigments (ochronosis). Since at present, further studies are necessary to support the use of drugs for the treatment of AKU, we investigated the effects of various anti-oxidants in counteracting melanin-like pigmentation and oxidative stress related to HGA and its metabolites.
  
  
  METHODS
  We set up an in vitro model using human serum treated with 0.33 mM HGA and tested the anti-oxidants ascorbic acid, N-acetylcysteine, phytic acid (PHY), taurine (TAU), ferulic acid (FER) and lipoic acid (LIP) for their ability to prevent or delay the production of melanin-like pigments, as well as to reduce oxidative post-translational modifications of proteins. Monitoring of intrinsic fluorescence of HGA-induced melanin-like pigments was used to evaluate the efficacy of compounds.
  
  
  RESULTS
  Our model allowed us to prove efficacy especially for PHY, TAU, LIP and FER in counteracting the production of HGA-induced melanin-like pigments and protein oxidation induced by HGA and its metabolites.
  
  
  CONCLUSIONS
  Our model allows the opening of new anti-oxidant therapeutic strategies to treat alkaptonuric ochronosis.
authors.affiliation: Dipartimento di Biologia Molecolare, Università degli Studi di Siena, via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Braconi
authors.forename: Marcella
authors.initials: M
authors.lastname: Laschi
authors.forename: Loredana
authors.initials: L
authors.lastname: Amato
authors.forename: Giulia
authors.initials: G
authors.lastname: Bernardini
authors.forename: Lia
authors.initials: L
authors.lastname: Millucci
authors.forename: Roberto
authors.initials: R
authors.lastname: Marcolongo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cavallo
authors.forename: Adriano
authors.initials: A
authors.lastname: Spreafico
authors.forename: Annalisa
authors.initials: A
authors.lastname: Santucci
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use; D000474:Alkaptonuria / Q000188:drug therapy*; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use; D002478:Cells, Cultured; D003373:Coumaric Acids / Q000627:therapeutic use; D006713:Homogentisic Acid / Q000378:metabolism*; D006801:Humans; D009794:Ochronosis / Q000188:drug therapy*; D018384:Oxidative Stress / Q000187:drug effects*; D010833:Phytic Acid / Q000627:therapeutic use; D050050:Protein Carbonylation / Q000187:drug effects*; D013654:Taurine / Q000627:therapeutic use; D008063:Thioctic Acid / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D003373:Coumaric Acids; D013654:Taurine; D008063:Thioctic Acid; D010833:Phytic Acid; C004999:ferulic acid; D006713:Homogentisic Acid; D001205:Ascorbic Acid; D000111:Acetylcysteine