Allopurinol Lowers Serum Urate but Does Not Reduce Oxidative Stress in CKD
Xanthine oxidase (XO) contributes to oxidative stress and vascular disease. Hyperuricemia and gout are common in patients with chronic kidney disease (CKD), a population at increased risk of vascular disease. We evaluated effects of allopurinol on serum XO activity and metabolome of CKD patients who...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/7/1297 |
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| author | Mingyao Sun Nicole Hines Diego Scerbo Jane Buchanan Chaorong Wu Patrick Ten Eyck Diana Zepeda-Orozco Eric B. Taylor Diana I. Jalal |
| author_facet | Mingyao Sun Nicole Hines Diego Scerbo Jane Buchanan Chaorong Wu Patrick Ten Eyck Diana Zepeda-Orozco Eric B. Taylor Diana I. Jalal |
| author_sort | Mingyao Sun |
| collection | DOAJ |
| description | Xanthine oxidase (XO) contributes to oxidative stress and vascular disease. Hyperuricemia and gout are common in patients with chronic kidney disease (CKD), a population at increased risk of vascular disease. We evaluated effects of allopurinol on serum XO activity and metabolome of CKD patients who had participated in a randomized double-blind clinical trial of allopurinol vs. placebo. XO activity was measured in participants’ serum. XO expression in venous endothelial cells was evaluated via immunofluorescence. Gas chromatography mass spectrometry (GC/MS) was utilized for metabolomics analysis. We found that in patients with stage 3 CKD and hyperuricemia, allopurinol lowered serum urate while increasing serum xanthine levels. Allopurinol, however, did not significantly suppress measured serum XO activity. Of note, baseline serum XO activity was low. Additionally, neither baseline serum XO activity nor XO protein expression were associated with measures of vascular dysfunction or with systemic or endothelial biomarkers of oxidative stress. Allopurinol affected several pathways, including pentose phosphate, pyrimidine, and tyrosine metabolism. Our findings suggest that circulating XO does not contribute to vascular disease in CKD patients. In addition to inhibition of XO activity, allopurinol was observed to impact other pathways; the implications of which require further study. |
| first_indexed | 2024-03-09T10:23:12Z |
| format | Article |
| id | doaj.art-691dff8abda647adb7c3ae188be1ad48 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T10:23:12Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-691dff8abda647adb7c3ae188be1ad482023-12-01T21:49:44ZengMDPI AGAntioxidants2076-39212022-06-01117129710.3390/antiox11071297Allopurinol Lowers Serum Urate but Does Not Reduce Oxidative Stress in CKDMingyao Sun0Nicole Hines1Diego Scerbo2Jane Buchanan3Chaorong Wu4Patrick Ten Eyck5Diana Zepeda-Orozco6Eric B. Taylor7Diana I. Jalal8Department of Internal Medicine, Division of Nephrology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USADepartment of Internal Medicine, Division of Nephrology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USADepartment of Molecular Physiology, University of Iowa, Iowa City, IA 52242, USADepartment of Molecular Physiology, University of Iowa, Iowa City, IA 52242, USAInstitute for Clinical and Translational Science, University of Iowa, Iowa City, IA 52242, USAInstitute for Clinical and Translational Science, University of Iowa, Iowa City, IA 52242, USACenter for Clinical and Translational Research, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USADepartment of Molecular Physiology, University of Iowa, Iowa City, IA 52242, USADepartment of Internal Medicine, Division of Nephrology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAXanthine oxidase (XO) contributes to oxidative stress and vascular disease. Hyperuricemia and gout are common in patients with chronic kidney disease (CKD), a population at increased risk of vascular disease. We evaluated effects of allopurinol on serum XO activity and metabolome of CKD patients who had participated in a randomized double-blind clinical trial of allopurinol vs. placebo. XO activity was measured in participants’ serum. XO expression in venous endothelial cells was evaluated via immunofluorescence. Gas chromatography mass spectrometry (GC/MS) was utilized for metabolomics analysis. We found that in patients with stage 3 CKD and hyperuricemia, allopurinol lowered serum urate while increasing serum xanthine levels. Allopurinol, however, did not significantly suppress measured serum XO activity. Of note, baseline serum XO activity was low. Additionally, neither baseline serum XO activity nor XO protein expression were associated with measures of vascular dysfunction or with systemic or endothelial biomarkers of oxidative stress. Allopurinol affected several pathways, including pentose phosphate, pyrimidine, and tyrosine metabolism. Our findings suggest that circulating XO does not contribute to vascular disease in CKD patients. In addition to inhibition of XO activity, allopurinol was observed to impact other pathways; the implications of which require further study.https://www.mdpi.com/2076-3921/11/7/1297xanthine oxidaseuratechronic kidney disease |
| spellingShingle | Mingyao Sun Nicole Hines Diego Scerbo Jane Buchanan Chaorong Wu Patrick Ten Eyck Diana Zepeda-Orozco Eric B. Taylor Diana I. Jalal Allopurinol Lowers Serum Urate but Does Not Reduce Oxidative Stress in CKD Antioxidants xanthine oxidase urate chronic kidney disease |
| title | Allopurinol Lowers Serum Urate but Does Not Reduce Oxidative Stress in CKD |
| title_full | Allopurinol Lowers Serum Urate but Does Not Reduce Oxidative Stress in CKD |
| title_fullStr | Allopurinol Lowers Serum Urate but Does Not Reduce Oxidative Stress in CKD |
| title_full_unstemmed | Allopurinol Lowers Serum Urate but Does Not Reduce Oxidative Stress in CKD |
| title_short | Allopurinol Lowers Serum Urate but Does Not Reduce Oxidative Stress in CKD |
| title_sort | allopurinol lowers serum urate but does not reduce oxidative stress in ckd |
| topic | xanthine oxidase urate chronic kidney disease |
| url | https://www.mdpi.com/2076-3921/11/7/1297 |
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