OBJECTIVES: 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.
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|Titolo:||Evaluation of anti-oxidant treatments in an in vitro model of alkaptonuric ochronosis|
|Citazione:||Braconi, D., Laschi, M., Amato, L., Bernardini, G., Millucci, L., Marcolongo, R., et al. (2010). Evaluation of anti-oxidant treatments in an in vitro model of alkaptonuric ochronosis. RHEUMATOLOGY, 49(10), 1975-1983.|
|Appare nelle tipologie:||1.1 Articolo in rivista|
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