Evaluation of antioxidant drugs for the treatment of ochronotic alkaptonuria in an in vitro human cell model

Journal of Cellular Physiology
Laura TintiAnnalisa Santucci

Abstract

Alkaptonuria (AKU) is a rare autosomal recessive disease, associated with deficiency of homogentisate 1,2-dioxygenase activity in the liver. This leads to an accumulation of homogentisic acid (HGA) and its oxidized derivatives in polymerized form in connective tissues especially in joints. Currently, AKU lacks an appropriate therapy. Hence, we propose a new treatment for AKU using the antioxidant N-acetylcysteine (NAC) administered in combinations with ascorbic acid (ASC) since it has been proven that NAC counteracts the side-effects of ASC. We established an in vitro cell model using human articular primary chondrocytes challenged with an excess of HGA (0.33 mM). We used this experimental model to undertake pre-clinical testing of potential antioxidative therapies for AKU, evaluating apoptosis, viability, proliferation, and metabolism of chondrocytes exposed to HGA and treated with NAC and ASC administered alone or in combination addition of both. NAC decreased apoptosis induced in chondrocytes by HGA, increased chondrocyte growth reduced by HGA, and partially restored proteoglycan release inhibited by HGA. A significantly improvement in efficacy was found with combined addition of the two antioxidants in comparison with NAC a...Continue Reading

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Citations

Jul 2, 2011·Journal of Inherited Metabolic Disease·Andrea Zatkova
Aug 30, 2011·Journal of Inherited Metabolic Disease·Daniela BraconiAnnalisa Santucci
May 31, 2014·Mediators of Inflammation·Lia MillucciAnnalisa Santucci
Jan 9, 2015·Diagnostic Pathology·Lia MillucciAnnalisa Santucci
Apr 15, 2015·Journal of Inherited Metabolic Disease·Lia MillucciAnnalisa Santucci
Mar 13, 2015·Journal of Inherited Metabolic Disease·Giulia BernardiniAnnalisa Santucci
Sep 28, 2016·Journal of Inherited Metabolic Disease·Lia MillucciAnnalisa Santucci
Oct 21, 2018·Journal of Cellular Physiology·Giulia BernardiniAnnalisa Santucci
Jul 29, 2010·Journal of Cellular Biochemistry·Daniela BraconiAnnalisa Santucci
Nov 12, 2013·Expert Review of Proteomics·Daniela BraconiAnnalisa Santucci
Aug 30, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Vittoria CicaloniAnnalisa Santucci
Jan 4, 2012·Journal of Cellular Physiology·Daniela BraconiAnnalisa Santucci
Nov 23, 2011·Journal of Cellular Physiology·Marcella LaschiAnnalisa Santucci
Jan 17, 2012·Proteomics·Giulia BernardiniAnnalisa Santucci
Jul 28, 2016·Journal of Cellular Physiology·Michela GeminianiAnnalisa Santucci
Mar 9, 2017·Calcified Tissue International·Lia MillucciAnnalisa Santucci
Oct 23, 2014·Journal of Cellular Physiology·Lia MillucciAnnalisa Santucci
Apr 17, 2021·Expert Review of Proteomics·Daniela BraconiAnnalisa Santucci

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