Clinical Trial and Research Center, People's Hospital of Baoan Shenzhen, Shenzhen, PR China.
Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China.
Pharmacol Res Perspect. 2021 May;9(3):e00764. doi: 10.1002/prp2.764.
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.
黄嘌呤氧化酶 (XO) 与硫嘌呤甲基转移酶 (TPMT) 和次黄嘌呤鸟嘌呤磷酸核糖转移酶 (HPRT) 竞争,以在体内代谢硫唑嘌呤 (AZA)/6-巯基嘌呤 (6-MP)。本研究进行了一项回顾性研究,以检测 XO 活性在接受硫嘌呤治疗的中国炎症性肠病 (IBD) 患者中的作用。我们还评估了 XO 活性与硫嘌呤诱导的不良反应 (AE) 发生率之间是否存在关系。从 140 例接受 AZA/6-MP 治疗前的 IBD 患者中收集临床数据和血液样本,并测量红细胞 XO 活性。所有患者的 XO 活性为 20.29±4.43 U/g Hb。未观察到 XO 活性的性别差异 (p=.728),且 UC 和 CD 患者的 XO 活性无差异 (p=.082)。41 例 (29.3%) 患者出现 AE,包括白细胞减少症 (26 例,18.57%)、胃肠道不耐受 (11 例,7.86%)、流感样症状 (5 例,3.57%)、脱发 (5 例,3.57%)和肝毒性 (1 例,0.71%)。有 AE 的患者的 XO 活性明显低于无 AE 的患者 (18.40±3.73 与 21.07±4.48 U/g Hb,p=.001),尤其是白细胞减少症患者 (18.29±3.68 与 21.07±4.48 U/g Hb,p=.004)。然而,有其他 AE 的患者的 XO 活性与无 AE 的患者之间无显著差异。发生流感样症状 (17.58±3.50 U/g Hb) 和脱发 (18.67±2.91 U/g Hb) 的患者的 XO 活性低于未发生的患者,但差异无统计学意义。这些发现表明,XO 表达降低的患者可能有发生硫嘌呤诱导毒性的高风险。