{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:20:44Z","timestamp":1793413244701,"version":"4.5.0"},"reference-count":132,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T00:00:00Z","timestamp":1623196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The accumulation of the uremic toxin indoxyl sulfate (IS) induces target organ damage in chronic kidney disease (CKD) patients, and causes complications including cardiovascular diseases, renal osteodystrophy, muscle wasting, and anemia. IS stimulates reactive oxygen species (ROS) production in CKD, which impairs glomerular filtration by a direct cytotoxic effect on the mesangial cells. IS further reduces antioxidant capacity in renal proximal tubular cells and contributes to tubulointerstitial injury. IS-induced ROS formation triggers the switching of vascular smooth muscular cells to the osteoblastic phenotype, which induces cardiovascular risk. Low-turnover bone disease seen in early CKD relies on the inhibitory effects of IS on osteoblast viability and differentiation, and osteoblastic signaling via the parathyroid hormone. Excessive ROS and inflammatory cytokine releases caused by IS directly inhibit myocyte growth in muscle wasting via myokines\u2019 effects. Moreover, IS triggers eryptosis via ROS-mediated oxidative stress, and elevates hepcidin levels in order to prevent iron flux in circulation in renal anemia. Thus, IS-induced oxidative stress underlies the mechanisms in CKD-related complications. This review summarizes the underlying mechanisms of how IS mediates oxidative stress in the pathogenesis of CKD\u2019s complications. Furthermore, we also discuss the potential role of oral AST-120 in attenuating IS-mediated oxidative stress after gastrointestinal adsorption of the IS precursor indole.<\/jats:p>","DOI":"10.3390\/antiox10060936","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T14:16:04Z","timestamp":1623248164000},"page":"936","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Indoxyl-Sulfate-Induced Redox Imbalance in Chronic Kidney Disease"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9452-5179","authenticated-orcid":false,"given":"Chien-Lin","family":"Lu","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Fu Jen Catholic University Hospital, New Taipei 24352, Taiwan"},{"name":"School of Medicine, Fu Jen Catholic University, New Taipei 242062, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0370-3951","authenticated-orcid":false,"given":"Cai-Mei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, Taipei Medical University Shuang Ho Hospital, New Taipei 23561, Taiwan"},{"name":"Research Center of Urology and Kidney, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7062-8560","authenticated-orcid":false,"given":"Kuo-Cheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 23142, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Tser","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Taoyuan Armed Forces General Hospital, Taoyuan 32551, Taiwan"},{"name":"National Defense Medical Center, Department of Pediatrics, Tri-Service General Hospital, Taipei 114202, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun-Lin","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan 32551, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Chieh","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Medicine, Fu Jen Catholic University, New Taipei 242062, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Poznyak, A.V., Grechko, A.V., Orekhova, V.A., Chegodaev, Y.S., Wu, W.K., and Orekhov, A.N. 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