文章基本信息

标题：Lack of xanthine dehydrogenase leads to a remarkable renal decline in a novel hypouricemic rat model
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作者：Lashodya V. Dissanayake ; Adrian Zietara ; Vladislav Levchenko 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：9
页码：1-19
DOI：10.1016/j.isci.2022.104887
语种：English
出版社：Elsevier
摘要：SummaryUric acid (UA) is the final metabolite in purine catabolism in humans. Previous studies have shown that the dysregulation of UA homeostasis is detrimental to cardiovascular and kidney health. TheXdhgene encodes for the Xanthine Oxidoreductase enzyme group, responsible for producing UA. To explore how hypouricemia can lead to kidney damage, we created a rat model with the genetic ablation of theXdhgene on the Dahl salt-sensitive rat background (SSXdh−/−). SSXdh−/−rats lacked UA and exhibited impairment in growth and survival. This model showed severe kidney injury with increased interstitial fibrosis, glomerular damage, crystal formation, and an inability to control electrolyte balance. Using a multi-omics approach, we highlighted that lack ofXdhleads to increased oxidative stress, renal cell proliferation, and inflammation. Our data reveal that the absence ofXdhleads to kidney damage and functional decline by the accumulation of purine metabolites in the kidney and increased oxidative stress.Graphical abstractDisplay OmittedHighlights•A novel rat model of hypouricemia was created by the gene ablation of theXdhgene•The SSXdh-/-rat showed a failure to thrive, kidney injury, and functional decline•Multi-omics revealed increased inflammation and oxidative stress in SSXdh-/-ratsBiological sciences; Molecular physiology; Molecular biology