{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:26:07Z","timestamp":1770747967850,"version":"3.49.0"},"reference-count":55,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T00:00:00Z","timestamp":1590364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Programme STAR, financially supported by UNINA and Compagnia San Paolo,","award":["E24E14000290005"],"award-info":[{"award-number":["E24E14000290005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Diabetic nephropathy (DN) is the primary cause of end-stage renal disease, worldwide, and oxidative stress has been recognized as a key factor in the pathogenesis and progression of DN. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase has the most important contribution to reactive oxygen species generation during the development of DN. Bioactive compound use has emerged as a potential approach to reduce chronic renal failure. Therefore, a red orange and lemon extract (RLE) rich in anthocyanins was chosen in our study, to reduce the toxic renal effects during the development of DN in Zucker diabetic fatty rat (ZDF). RLE effects were examined daily for 24 weeks, through gavage, in ZDF rats treated with RLE (90 mg\/kg). At the end of the experiment, ZDF rats treated with RLE showed a reduction of the diabetes-associated up-regulation of both NOX4 and the p47-phox and p22-phox subunits, and restored the BAX\/BCL-2 ratio respect to ZDF rats. Furthermore, RLE was able to reduce the oxidative DNA damage measured in urine samples in ZDF rats. This study showed that RLE could prevent the renal damage induced by DN through its capacity to inhibit NOX4 and apoptosis mechanisms.<\/jats:p>","DOI":"10.3390\/jcm9051600","type":"journal-article","created":{"date-parts":[[2020,5,25]],"date-time":"2020-05-25T11:42:02Z","timestamp":1590406922000},"page":"1600","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Effects of a Red Orange and Lemon Extract in Obese Diabetic Zucker Rats: Role of Nicotinamide Adenine Dinucleotide Phosphate Oxidase"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7798-7710","authenticated-orcid":false,"given":"Sara","family":"Damiano","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine and Animal Productions, University of Naples \u201cFederico II\u201d, 80137 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4580-9594","authenticated-orcid":false,"given":"Chiara","family":"Lauritano","sequence":"additional","affiliation":[{"name":"Marine Biotechnology Department, Stazione Zoologica Anton Dohrn, 80121 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0788-4107","authenticated-orcid":false,"given":"Consiglia","family":"Longobardi","sequence":"additional","affiliation":[{"name":"Department of Mental, Physical Health and Preventive Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4402-0914","authenticated-orcid":false,"given":"Emanuela","family":"Andretta","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Productions, University of Naples \u201cFederico II\u201d, 80137 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali Murat","family":"Elagoz","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Neurobiology, Department of Biology, Faculty of Science, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Rapisarda","sequence":"additional","affiliation":[{"name":"Council for Agricultural Research and Economics (CREA), Research Centre for Olive, Citrus and Tree Fruit, 95024 Acireale, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mattia","family":"Di Iorio","sequence":"additional","affiliation":[{"name":"Independent Researcher, 83100 Avellino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Florio","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Productions, University of Naples \u201cFederico II\u201d, 80137 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4121-4905","authenticated-orcid":false,"given":"Roberto","family":"Ciarcia","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Productions, University of Naples \u201cFederico II\u201d, 80137 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1007\/s001250100561","article-title":"Podocyte foot process broadening in experimental diabetic nephropathy: Amelioration with renin-angiotensin blockade","volume":"44","author":"Gilbert","year":"2001","journal-title":"Diabetologia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.3390\/md12031512","article-title":"Anti-Diabetic Effects of CTB-APSL Fusion Protein in Type 2 Diabetic Mice","volume":"12","author":"Liu","year":"2014","journal-title":"Mar. 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