{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T19:16:46Z","timestamp":1785784606476,"version":"3.56.0"},"reference-count":71,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission Seventh Framework Programme","doi-asserted-by":"publisher","award":["304985"],"award-info":[{"award-number":["304985"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission Seventh Framework Programme","doi-asserted-by":"publisher","award":["PSR 2021 F-CUR"],"award-info":[{"award-number":["PSR 2021 F-CUR"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Siena","award":["304985"],"award-info":[{"award-number":["304985"]}]},{"name":"University of Siena","award":["PSR 2021 F-CUR"],"award-info":[{"award-number":["PSR 2021 F-CUR"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Nitisinone (NTBC) was recently approved to treat alkaptonuria (AKU), but there is no information on its impact on oxidative stress and inflammation, which are observed in AKU. Therefore, serum samples collected during the clinical studies SONIA1 (40 AKU patients) and SONIA2 (138 AKU patients) were tested for Serum Amyloid A (SAA), CRP and IL-8 by ELISA; Advanced Oxidation Protein Products (AOPP) by spectrophotometry; and protein carbonyls by Western blot. Our results show that NTBC had no significant effects on the tested markers except for a slight but statistically significant effect for NTBC, but not for the combination of time and NTBC, on SAA levels in SONIA2 patients. Notably, the majority of SONIA2 patients presented with SAA &gt; 10 mg\/L, and 30 patients in the control group (43.5%) and 40 patients (58.0%) in the NTBC-treated group showed persistently elevated SAA &gt; 10 mg\/L at each visit during SONIA2. Higher serum SAA correlated with lower quality of life and higher morbidity. Despite no quantitative differences in AOPP, the preliminary analysis of protein carbonyls highlighted patterns that deserve further investigation. Overall, our results suggest that NTBC cannot control the sub-clinical inflammation due to increased SAA observed in AKU, which is also a risk factor for developing secondary amyloidosis.<\/jats:p>","DOI":"10.3390\/cells11223668","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T03:11:21Z","timestamp":1669000281000},"page":"3668","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effects of Nitisinone on Oxidative and Inflammatory Markers in Alkaptonuria: Results from SONIA1 and SONIA2 Studies"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9657-4169","authenticated-orcid":false,"given":"Daniela","family":"Braconi","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6910-0056","authenticated-orcid":false,"given":"Michela","family":"Geminiani","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eftychia Eirini","family":"Psarelli","sequence":"additional","affiliation":[{"name":"Liverpool Clinical Trials Centre, University of Liverpool, Liverpool L69 3BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4929-5316","authenticated-orcid":false,"given":"Daniela","family":"Giustarini","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Marzocchi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy"},{"name":"UOC Clinical Pathology, Siena University Hospital, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranieri","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0016-0728","authenticated-orcid":false,"given":"Giulia","family":"Bernardini","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0263-7107","authenticated-orcid":false,"given":"Ottavia","family":"Spiga","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal Biology, University of Liverpool, Liverpool L69 3BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim-Hanh","family":"Le Quan Sang","sequence":"additional","affiliation":[{"name":"H\u00f4pital Necker-Enfants Malades, CEDEX 15, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1826-2810","authenticated-orcid":false,"given":"Jean-Baptiste","family":"Arnoux","sequence":"additional","affiliation":[{"name":"H\u00f4pital Necker-Enfants Malades, CEDEX 15, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1747-7150","authenticated-orcid":false,"given":"Richard","family":"Imrich","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Slovak Academy of Sciences, 845 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed S.","family":"Al-Sbou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Alkaptonuria Research Office, Faculty of Medicine, Mutah University, Mutah, Karak 61710, Jordan"},{"name":"College of Medicine, Ajman University, Ajman P.O. Box 346, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Gornall","sequence":"additional","affiliation":[{"name":"Liverpool Clinical Trials Centre, University of Liverpool, Liverpool L69 3BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Jackson","sequence":"additional","affiliation":[{"name":"Liverpool Clinical Trials Centre, University of Liverpool, Liverpool L69 3BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshminarayan R.","family":"Ranganath","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal Biology, University of Liverpool, Liverpool L69 3BX, UK"},{"name":"Department of Clinical Biochemistry and Metabolism, Royal Liverpool University Hospital, Liverpool L7 8XP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6976-9086","authenticated-orcid":false,"given":"Annalisa","family":"Santucci","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1056\/NEJMoa021736","article-title":"Natural history of alkaptonuria","volume":"347","author":"Phornphutkul","year":"2002","journal-title":"N. 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