Unveiling the Emerging Role of Xanthine Oxidase in Acute Pancreatitis: Beyond Reactive Oxygen Species

Acute pancreatitis (AP) is a potentially fatal acute digestive disease that is widespread globally. Although significant progress has been made in the previous decade, the study of mechanisms and therapeutic strategies is still far from being completed. Xanthine oxidase (XO) is an enzyme that cataly...

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Main Authors: Chenxia Han, Yaling Wu, Juan Rong, Qing Xia, Dan Du
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Antioxidants
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Online Access:https://www.mdpi.com/2076-3921/14/1/95
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author Chenxia Han
Yaling Wu
Juan Rong
Qing Xia
Dan Du
author_facet Chenxia Han
Yaling Wu
Juan Rong
Qing Xia
Dan Du
author_sort Chenxia Han
collection DOAJ
description Acute pancreatitis (AP) is a potentially fatal acute digestive disease that is widespread globally. Although significant progress has been made in the previous decade, the study of mechanisms and therapeutic strategies is still far from being completed. Xanthine oxidase (XO) is an enzyme that catalyzes hypoxanthine and xanthine to produce urate and is accompanied by the generation of reactive oxygen species (ROS) in purine catabolism. Considerable preclinical and clinical studies have been conducted over many decades to investigate the role of XO in the pathogenesis of AP and its potential targeting therapeutic value. There is no doubt that the ROS generated by irreversibly activated XO participates in the local pancreas and multiple organ failure during AP. However, the optimal timing and doses for therapeutic interventions targeting XO in animal studies and the clinic, as well as the additional molecular mechanisms through which XO contributes to disease onset and progression, including metabolic regulation, remain to be elucidated. This review summarized the benefits and contradictions of using XO inhibitors in animal models, offered mechanisms other than ROS, and discussed the difficulties faced in clinical trials. We hope to provide a perspective on the future worthwhile basic and clinical research on XO by analyzing its chemical and biological characteristics, as well as the progress of its regulatory mechanisms in AP.
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spelling doaj-art-80b6471d8f6143919dcd8db621daf96a2025-01-24T13:19:28ZengMDPI AGAntioxidants2076-39212025-01-011419510.3390/antiox14010095Unveiling the Emerging Role of Xanthine Oxidase in Acute Pancreatitis: Beyond Reactive Oxygen SpeciesChenxia Han0Yaling Wu1Juan Rong2Qing Xia3Dan Du4West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, ChinaFrontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, ChinaDepartment of Gastroenterology, The Third People’s Hospital of Chengdu, Chengdu 610031, ChinaWest China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, ChinaFrontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, ChinaAcute pancreatitis (AP) is a potentially fatal acute digestive disease that is widespread globally. Although significant progress has been made in the previous decade, the study of mechanisms and therapeutic strategies is still far from being completed. Xanthine oxidase (XO) is an enzyme that catalyzes hypoxanthine and xanthine to produce urate and is accompanied by the generation of reactive oxygen species (ROS) in purine catabolism. Considerable preclinical and clinical studies have been conducted over many decades to investigate the role of XO in the pathogenesis of AP and its potential targeting therapeutic value. There is no doubt that the ROS generated by irreversibly activated XO participates in the local pancreas and multiple organ failure during AP. However, the optimal timing and doses for therapeutic interventions targeting XO in animal studies and the clinic, as well as the additional molecular mechanisms through which XO contributes to disease onset and progression, including metabolic regulation, remain to be elucidated. This review summarized the benefits and contradictions of using XO inhibitors in animal models, offered mechanisms other than ROS, and discussed the difficulties faced in clinical trials. We hope to provide a perspective on the future worthwhile basic and clinical research on XO by analyzing its chemical and biological characteristics, as well as the progress of its regulatory mechanisms in AP.https://www.mdpi.com/2076-3921/14/1/95xanthine oxidaseacute pancreatitisdrug targetcellular mechanismmultiple organ failure
spellingShingle Chenxia Han
Yaling Wu
Juan Rong
Qing Xia
Dan Du
Unveiling the Emerging Role of Xanthine Oxidase in Acute Pancreatitis: Beyond Reactive Oxygen Species
Antioxidants
xanthine oxidase
acute pancreatitis
drug target
cellular mechanism
multiple organ failure
title Unveiling the Emerging Role of Xanthine Oxidase in Acute Pancreatitis: Beyond Reactive Oxygen Species
title_full Unveiling the Emerging Role of Xanthine Oxidase in Acute Pancreatitis: Beyond Reactive Oxygen Species
title_fullStr Unveiling the Emerging Role of Xanthine Oxidase in Acute Pancreatitis: Beyond Reactive Oxygen Species
title_full_unstemmed Unveiling the Emerging Role of Xanthine Oxidase in Acute Pancreatitis: Beyond Reactive Oxygen Species
title_short Unveiling the Emerging Role of Xanthine Oxidase in Acute Pancreatitis: Beyond Reactive Oxygen Species
title_sort unveiling the emerging role of xanthine oxidase in acute pancreatitis beyond reactive oxygen species
topic xanthine oxidase
acute pancreatitis
drug target
cellular mechanism
multiple organ failure
url https://www.mdpi.com/2076-3921/14/1/95
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AT yalingwu unveilingtheemergingroleofxanthineoxidaseinacutepancreatitisbeyondreactiveoxygenspecies
AT juanrong unveilingtheemergingroleofxanthineoxidaseinacutepancreatitisbeyondreactiveoxygenspecies
AT qingxia unveilingtheemergingroleofxanthineoxidaseinacutepancreatitisbeyondreactiveoxygenspecies
AT dandu unveilingtheemergingroleofxanthineoxidaseinacutepancreatitisbeyondreactiveoxygenspecies