Allopurinol Lowers Serum Urate but Does Not Reduce Oxidative Stress in CKD

Mingyao Sun; Nicole Hines; Diego Scerbo; Jane Buchanan; Chaorong Wu; Patrick Ten Eyck; Diana Zepeda-Orozco; Eric B Taylor; Diana I Jalal

doi:10.3390/antiox11071297

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Allopurinol Lowers Serum Urate but Does Not Reduce Oxidative Stress in CKD

Journal article

Open access

Peer reviewed

Allopurinol Lowers Serum Urate but Does Not Reduce Oxidative Stress in CKD

Mingyao Sun, Nicole Hines, Diego Scerbo, Jane Buchanan, Chaorong Wu, Patrick Ten Eyck, Diana Zepeda-Orozco, Eric B Taylor and Diana I Jalal

Antioxidants, Vol.11(7), p.1297

06/29/2022

DOI: 10.3390/antiox11071297

PMCID: PMC9312025

PMID: 35883787

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Abstract

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.

Details

Title: Subtitle: Allopurinol Lowers Serum Urate but Does Not Reduce Oxidative Stress in CKD
Creators: Mingyao Sun - Roy J. and Lucille A. Carver College of Medicine
Nicole Hines
Diego Scerbo
Jane Buchanan
Chaorong Wu
Patrick Ten Eyck
Diana Zepeda-Orozco
Eric B Taylor
Diana I Jalal
Resource Type: Journal article
Publication Details: Antioxidants, Vol.11(7), p.1297
DOI: 10.3390/antiox11071297
PMID: 35883787
PMCID: PMC9312025
NLM abbreviation: Antioxidants (Basel)
ISSN: 2076-3921
eISSN: 2076-3921
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: T32 DK007690, K23DK088833, R01HL134738, R01 DK104998, UL1TR002537
Language: English
Date published: 06/29/2022
Academic Unit: Molecular Physiology and Biophysics; Pathology; Biostatistics; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Nephrology; Internal Medicine
Record Identifier: 9984297497802771

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