{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T18:22:32Z","timestamp":1761675752073},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2010,5,27]],"date-time":"2010-05-27T00:00:00Z","timestamp":1274918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2010,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alkaptonuria (AKU) is a rare autosomal recessive disease, associated with deficiency of homogentisate 1,2\u2010dioxygenase 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 <jats:italic>N<\/jats:italic>\u2010acetylcysteine (NAC) administered in combinations with ascorbic acid (ASC) since it has been proven that NAC counteracts the side\u2010effects of ASC. We established an <jats:italic>in vitro<\/jats:italic> cell model using human articular primary chondrocytes challenged with an excess of HGA (0.33\u2009mM). We used this experimental model to undertake pre\u2010clinical 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 and ASC alone. Our novel <jats:italic>in vitro<\/jats:italic> AKU model allowed us to demonstrate the efficacy of the co\u2010administration of NAC and ASC to counteract the negative effects of HGA for the treatment of ochronotic arthropathy. J. Cell. Physiol. 225: 84\u201391, 2010. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.22199","type":"journal-article","created":{"date-parts":[[2010,5,27]],"date-time":"2010-05-27T14:46:49Z","timestamp":1274971609000},"page":"84-91","source":"Crossref","is-referenced-by-count":46,"title":["Evaluation of antioxiodant drugs for the treatment of ochronotic alkaptonuria in an <i>in vitro<\/i> human cell model"],"prefix":"10.1002","volume":"225","author":[{"given":"Laura","family":"Tinti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriano","family":"Spreafico","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Braconi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lia","family":"Millucci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Bernardini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Chellini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Cavallo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Selvi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauro","family":"Galeazzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Marcolongo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James A.","family":"Gallagher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annalisa","family":"Santucci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,7,15]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"4","article-title":"Chondrocyte growth inhibition induced by homogentisic acid and its partial prevention with ascorbic acid","volume":"16","author":"Angeles AP","year":"1989","journal-title":"J Rheumatol"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.200305844"},{"key":"e_1_2_6_5_1","first-page":"269","article-title":"N\u2010acetylcysteine and vitamin E: An in vitro study of their effect on homogentisic acid polymerization","volume":"21","author":"Chindamo D","year":"2003","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(20001201)88:5<702::AID-IJC4>3.0.CO;2-3"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-8981(03)00003-2"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.240590806"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005410416482"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(86)90368-6"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0996-19"},{"key":"e_1_2_6_12_1","first-page":"289","article-title":"Alkaptonuria and ochronosis in three siblings. 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