Indoxyl-Sulfate-Induced Redox Imbalance in Chronic Kidney Disease
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,...
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| Format: | Article |
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MDPI AG
2021-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/6/936 |
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| author | Chien-Lin Lu Cai-Mei Zheng Kuo-Cheng Lu Min-Tser Liao Kun-Lin Wu Ming-Chieh Ma |
| author_facet | Chien-Lin Lu Cai-Mei Zheng Kuo-Cheng Lu Min-Tser Liao Kun-Lin Wu Ming-Chieh Ma |
| author_sort | Chien-Lin Lu |
| collection | DOAJ |
| description | 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’ 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’s 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. |
| first_indexed | 2024-03-10T10:34:18Z |
| format | Article |
| id | doaj.art-907486df101f4c71a867b1ae0a428692 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T10:34:18Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-907486df101f4c71a867b1ae0a4286922023-11-21T23:27:13ZengMDPI AGAntioxidants2076-39212021-06-0110693610.3390/antiox10060936Indoxyl-Sulfate-Induced Redox Imbalance in Chronic Kidney DiseaseChien-Lin Lu0Cai-Mei Zheng1Kuo-Cheng Lu2Min-Tser Liao3Kun-Lin Wu4Ming-Chieh Ma5Division of Nephrology, Department of Medicine, Fu Jen Catholic University Hospital, New Taipei 24352, TaiwanDivision of Nephrology, Department of Internal Medicine, College of Medicine, Taipei Medical University, Taipei 11031, TaiwanDivision of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 23142, TaiwanDepartment of Pediatrics, Taoyuan Armed Forces General Hospital, Taoyuan 32551, TaiwanDivision of Nephrology, Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan 32551, TaiwanSchool of Medicine, Fu Jen Catholic University, New Taipei 242062, TaiwanThe 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’ 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’s 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.https://www.mdpi.com/2076-3921/10/6/936AST-120chronic kidney diseaseindoxyl sulfateoxidative stress |
| spellingShingle | Chien-Lin Lu Cai-Mei Zheng Kuo-Cheng Lu Min-Tser Liao Kun-Lin Wu Ming-Chieh Ma Indoxyl-Sulfate-Induced Redox Imbalance in Chronic Kidney Disease Antioxidants AST-120 chronic kidney disease indoxyl sulfate oxidative stress |
| title | Indoxyl-Sulfate-Induced Redox Imbalance in Chronic Kidney Disease |
| title_full | Indoxyl-Sulfate-Induced Redox Imbalance in Chronic Kidney Disease |
| title_fullStr | Indoxyl-Sulfate-Induced Redox Imbalance in Chronic Kidney Disease |
| title_full_unstemmed | Indoxyl-Sulfate-Induced Redox Imbalance in Chronic Kidney Disease |
| title_short | Indoxyl-Sulfate-Induced Redox Imbalance in Chronic Kidney Disease |
| title_sort | indoxyl sulfate induced redox imbalance in chronic kidney disease |
| topic | AST-120 chronic kidney disease indoxyl sulfate oxidative stress |
| url | https://www.mdpi.com/2076-3921/10/6/936 |
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