ArticleJCI insight2021
Increased plasma XOR activity induced by NAFLD/NASH and its possible involvement in vascular neointimal proliferation.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Effect of the Xanthine Oxidase Inhibitor Febuxostat on the Cardio-Ankle Vascular Index in Asymptomatic Patients with Hyperuricemia and Liver Dysfunction: A Sub-Analysis of the PRIZE Study.Journal of atherosclerosis and thrombosis · 2025Trial
- Associations between muscle quality and whole-body vibration exercise-induced changes in plasma hypoxanthine following an oral glucose load in healthy male subjects.Endocrine journal · 2025Trial
- Positive association between serum uric acid and metabolic dysfunction-associated steatotic liver disease: insights from a Japanese health checkup cohort.BMC endocrine disorders · 2026Article
- Xanthine oxidoreductase activity in MASLD: links to lipid metabolism, oxidative stress, and inflammation.Frontiers in endocrinology · 2026Article
- Association of hepatic steatosis with increased plasma xanthine oxidoreductase activity: MedCity21 health examination registry.Metabolism open · 2025Article
- Exploring the role of xanthine oxidase and aldehyde oxidase in metabolic dysfunction-associated steatotic liver disease (MASLD).Journal of molecular histology · 2025Review
- Hyperuricemia-Especially "Metabolic Hyperuricemia"-Is Independently Associated with a Higher Risk of Steatotic Liver Disease.Metabolites · 2025Article
- Implication of xanthine oxidoreductase in oxidative stress-related chronic diseases.Frontiers in endocrinology · 2025Review
- Decoding the fatty liver-hyperuricemia link in the obese and nonobese hypertensive patients: insights from a cohort study.Scientific reports · 2024Article
- Role ofAntioxidants (Basel, Switzerland) · 2024Article
- Integrated Microbiome and Metabolome Analysis Reveals Hypothalamic-Comorbidities Related Signatures in Craniopharyngioma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Sex- and age-associated factors drive the pathophysiology of MASLD.Hepatology communications · 2024Article
- Emerging Roles of Xanthine Oxidoreductase in Chronic Kidney Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Naringenin prevents non-alcoholic steatohepatitis by modulating the host metabolome and intestinal microbiome in MCD diet-fed mice.Food science & nutrition · 2023Article
- Human Plasma Xanthine Oxidoreductase Activity in Cardiovascular Disease: Evidence from a Population-Based Study.Biomedicines · 2023Review
- Article
- Non-alcoholic fatty liver disease and liver secretome.Archives of pharmacal research · 2022Review
- Association of Metabolomic Change and Treatment Response in Patients with Non-Alcoholic Fatty Liver Disease.Biomedicines · 2022Article
- Impact of hyperuricemia on chronic kidney disease and atherosclerotic cardiovascular disease.Hypertension research : official journal of the Japanese Society of Hypertension · 2022Review
- Improved effect of fresh ginseng paste (radix ginseng-ziziphus jujube) on hyperuricemia based on network pharmacology and molecular docking.Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Xanthine oxidoreductase (XOR) is an enzyme that catalyzes hypoxanthine to xanthine and xanthine to uric acid, respectively. However, the underlying mechanisms of increased plasma XOR and its pathological roles in systemic diseases, such as atherosclerosis, are not fully understood. In this study, we found that changes in plasma XOR activity after bariatric surgery closely associated with those in liver enzymes, but not with those in BMI. In a mouse model of nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH), plasma XOR activity markedly increased. Besides, purine catabolism was accelerated in the plasma per se of NASH mice and human patients with high XOR activity. In our NASH mice, we observed an increased vascular neointima formation consisting of dedifferentiated vascular smooth muscle cells (SMCs), which was significantly attenuated by topiroxostat, a selective XOR inhibitor. In vitro, human liver S9-derived XOR promoted proliferation of SMCs with phenotypic modulation and induced ROS production by catabolizing hypoxanthine released from human endothelial cells. Collectively, the results from human and mouse models suggest that increased plasma XOR activity, mainly explained by excess hepatic leakage, was involved in the pathogenesis of vascular injury, especially in NAFLD/NASH conditions.
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