Evaluation of anti-oxidant treatments in an in vitro model of alkaptonuric ochronosis.
نویسندگان
چکیده
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.
منابع مشابه
Alkaptonuric ochronosis: a case report.
Alkaptonuric ochronosis is a rare autosomal recessive metabolic disorder resulting in a deficiency of homogentisic acid oxidase (alkaptonuria). Ultimately, this enzyme deficiency enables homogentisic acid to accumulate, become polymerized, and be systemically deposited within various tissues of the body (ochronosis). As the disease progresses, tissue deposition of polymerized homogentisic acid ...
متن کاملNeglected Alkaptonuric Patient Presenting with Steppage Gait
Even though intervertebral disc degeneration can be found in the natural course of alkaptonuria, detection of the disease by black disc color change in a patient without any other presentation of alkaptonuria is an exceptionally rare condition. We have reported a very rare case of alkaptonuria presented with low back pain and steppage gait in a 51-year-old male with a complaint of chronic low...
متن کاملAlkaptonuric Ochronosis.
Alkaptonuria is an autosomal recessive metabolic disorder characterized by joints and spine involvement, ochronosis and presence of homogentisic acid in urine and its deposition in cartilage, intervertebral disc and other connective tissues, leading to disabling arthritis in elderly individual.
متن کاملگزارش یک مورد اکرونوزیس آلکاپتونوریک
F Abbasi [1] , Ph.D S Naji [2] , Ph.D F Mirzatolui [3] , MD G Behjati [4] , Ph.D Received: 28 April, 2008 Accepted: 5 Nov, 2008 Abstract Alkaptonuria is a rare autosomal recessive disorder characterized by deficiency of homogentisic acid oxidase. This deficiency leads to accumulation of homogentisic acid in tissues and its urinary excretion and resulting in characteristic features like o...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Rheumatology
دوره 49 10 شماره
صفحات -
تاریخ انتشار 2010