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Xanthine oxidase activity in thiopurine curative Chinese inflammatory bowel disease patients

Xanthine oxidase (XO) competes with thiopurine S‐methyltransferase (TPMT) and hypoxanthine guanine phosphoribosyltransferase (HPRT) to metabolize azathioprine (AZA)/6‐mercaptopurine (6‐MP) in vivo. A retrospective investigation was performed to detect the activity of XO in thiopurine curative Chines...

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Autores principales: Ding, Liang, Zhang, Fang‐bin, Liu, Hui, Gao, Xiang, Bi, Hui‐chang, Huang, Ling, Wang, Xue‐ding, Chen, Bai‐li, Zhang, Yu, Lv, Chuanzhu, Hu, Pin‐jin, Huang, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085934/
https://www.ncbi.nlm.nih.gov/pubmed/33929082
http://dx.doi.org/10.1002/prp2.764
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author Ding, Liang
Zhang, Fang‐bin
Liu, Hui
Gao, Xiang
Bi, Hui‐chang
Huang, Ling
Wang, Xue‐ding
Chen, Bai‐li
Zhang, Yu
Lv, Chuanzhu
Hu, Pin‐jin
Huang, Min
author_facet Ding, Liang
Zhang, Fang‐bin
Liu, Hui
Gao, Xiang
Bi, Hui‐chang
Huang, Ling
Wang, Xue‐ding
Chen, Bai‐li
Zhang, Yu
Lv, Chuanzhu
Hu, Pin‐jin
Huang, Min
author_sort Ding, Liang
collection PubMed
description Xanthine oxidase (XO) competes with thiopurine S‐methyltransferase (TPMT) and hypoxanthine guanine phosphoribosyltransferase (HPRT) to metabolize azathioprine (AZA)/6‐mercaptopurine (6‐MP) in vivo. A retrospective investigation was performed to detect the activity of XO in thiopurine curative Chinese inflammatory bowel disease (IBD) patients. We also evaluated whether a relationship between XO activity and incidence of thiopurine‐induced adverse effects (AEs) existed. Clinical data and blood samples were collected from 140 IBD patients before receiving AZA/6‐MP therapy, and the erythrocyte XO activity was measured. The XO activities of all patients were 20.29 ± 4.43 U/g Hb. No sex difference in XO activity was observed (p = .728), and the XO activity showed no difference between the UC and CD patients (p = .082). AEs were observed in 41 (29.3%) patients including leukopenia (26, 18.57%), gastrointestinal intolerance (11, 7.86%), flu‐like symptom (5, 3.57%), alopecia (5, 3.57%), and hepatotoxicity (1, 0.71%). XO activity was significantly lower in the patients with AEs than in those without AEs (18.40 ± 3.73 vs. 21.07 ± 4.48 U/g Hb, p = .001), especially in the patients with leukopenia (18.29 ± 3.68 vs. 21.07 ± 4.48 U/g Hb, p = .004). However, no significant difference in XO activity was found between patients with and without other AEs. Decreased XO activity was observed in the patients who developed flu‐like symptoms (17.58 ± 3.50 U/g Hb) and alopecia (18.67 ± 2.91 U/g Hb) compared to those who did not, although the differences did not reach statistical significance. These findings suggested that patients with low XO expression might have a high risk of thiopurine‐induced toxicity.
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spelling pubmed-80859342021-05-07 Xanthine oxidase activity in thiopurine curative Chinese inflammatory bowel disease patients Ding, Liang Zhang, Fang‐bin Liu, Hui Gao, Xiang Bi, Hui‐chang Huang, Ling Wang, Xue‐ding Chen, Bai‐li Zhang, Yu Lv, Chuanzhu Hu, Pin‐jin Huang, Min Pharmacol Res Perspect Original Articles Xanthine oxidase (XO) competes with thiopurine S‐methyltransferase (TPMT) and hypoxanthine guanine phosphoribosyltransferase (HPRT) to metabolize azathioprine (AZA)/6‐mercaptopurine (6‐MP) in vivo. A retrospective investigation was performed to detect the activity of XO in thiopurine curative Chinese inflammatory bowel disease (IBD) patients. We also evaluated whether a relationship between XO activity and incidence of thiopurine‐induced adverse effects (AEs) existed. Clinical data and blood samples were collected from 140 IBD patients before receiving AZA/6‐MP therapy, and the erythrocyte XO activity was measured. The XO activities of all patients were 20.29 ± 4.43 U/g Hb. No sex difference in XO activity was observed (p = .728), and the XO activity showed no difference between the UC and CD patients (p = .082). AEs were observed in 41 (29.3%) patients including leukopenia (26, 18.57%), gastrointestinal intolerance (11, 7.86%), flu‐like symptom (5, 3.57%), alopecia (5, 3.57%), and hepatotoxicity (1, 0.71%). XO activity was significantly lower in the patients with AEs than in those without AEs (18.40 ± 3.73 vs. 21.07 ± 4.48 U/g Hb, p = .001), especially in the patients with leukopenia (18.29 ± 3.68 vs. 21.07 ± 4.48 U/g Hb, p = .004). However, no significant difference in XO activity was found between patients with and without other AEs. Decreased XO activity was observed in the patients who developed flu‐like symptoms (17.58 ± 3.50 U/g Hb) and alopecia (18.67 ± 2.91 U/g Hb) compared to those who did not, although the differences did not reach statistical significance. These findings suggested that patients with low XO expression might have a high risk of thiopurine‐induced toxicity. John Wiley and Sons Inc. 2021-04-30 /pmc/articles/PMC8085934/ /pubmed/33929082 http://dx.doi.org/10.1002/prp2.764 Text en © 2021 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Ding, Liang
Zhang, Fang‐bin
Liu, Hui
Gao, Xiang
Bi, Hui‐chang
Huang, Ling
Wang, Xue‐ding
Chen, Bai‐li
Zhang, Yu
Lv, Chuanzhu
Hu, Pin‐jin
Huang, Min
Xanthine oxidase activity in thiopurine curative Chinese inflammatory bowel disease patients
title Xanthine oxidase activity in thiopurine curative Chinese inflammatory bowel disease patients
title_full Xanthine oxidase activity in thiopurine curative Chinese inflammatory bowel disease patients
title_fullStr Xanthine oxidase activity in thiopurine curative Chinese inflammatory bowel disease patients
title_full_unstemmed Xanthine oxidase activity in thiopurine curative Chinese inflammatory bowel disease patients
title_short Xanthine oxidase activity in thiopurine curative Chinese inflammatory bowel disease patients
title_sort xanthine oxidase activity in thiopurine curative chinese inflammatory bowel disease patients
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085934/
https://www.ncbi.nlm.nih.gov/pubmed/33929082
http://dx.doi.org/10.1002/prp2.764
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