Department of Pharmacology, Faculty of Medicine, Cairo University, 74 A Tereet Elzomor Haram, Giza, Egypt.
Dig Dis Sci. 2013 Mar;58(3):650-9. doi: 10.1007/s10620-012-2391-1. Epub 2012 Sep 26.
Xanthine oxidase has been implicated in the pathogenesis of a wide spectrum of diseases, and is thought to be the most important source of oxygen-free radicals and cell damage during re-oxygenation of hypoxic tissues.
The present study was undertaken to demonstrate whether febuxostat is superior to allopurinol in prevention of the local and remote harmful effects of small intestinal ischemia/reperfusion injury in rats.
Intestinal ischemia was induced by superior mesenteric artery ligation. The rats were assigned to five groups: the sham control; the intestinal ischemia/reperfusion; the allopurinol; and the febuxostat 5 and 10 mg/kg pretreated ischemia/reperfusion groups. Treatment was administered from 7 days before ischemia induction. After the reperfusion, the serum and tissues were obtained for biochemical, pharmacological, and histological studies.
Intestinal reperfusion led to an elevation in the serum levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, malondialdehyde, and xanthine oxidase as well as intestinal myeloperoxidase, malonadialdehyde, and xanthine oxidase/xanthine dehydrogenase activity. Furthermore, the ischemia/reperfusion induced a reduction in the contractile responsiveness to acetylcholine. These changes were significantly regulated by the pretreatment with febuxostat compared to allopurinol. The degree of pathological impairment in the intestinal mucosa, liver, and lung tissues were lighter in the pretreated groups.
Febuxostat may offer advantages over allopurinol in lessening local intestinal injury as well as remote hepatic and lung injuries induced by small intestinal ischemia/reperfusion.
黄嘌呤氧化酶与广泛的疾病发病机制有关，被认为是低氧组织再氧合过程中氧自由基和细胞损伤的最重要来源。
本研究旨在证明别嘌醇在预防大鼠小肠缺血/再灌注损伤的局部和远处有害影响方面是否优于非布司他。
通过肠系膜上动脉结扎诱导肠缺血。将大鼠分为五组：假手术对照；肠缺血/再灌注；别嘌醇；以及非布司他 5 和 10mg/kg 预处理缺血/再灌注组。治疗从缺血诱导前 7 天开始。再灌注后，采集血清和组织进行生化、药理学和组织学研究。
肠再灌注导致血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、肿瘤坏死因子-α、丙二醛和黄嘌呤氧化酶以及肠髓过氧化物酶、丙二醛和黄嘌呤氧化酶/黄嘌呤脱氢酶活性升高。此外，缺血/再灌注导致对乙酰胆碱的收缩反应性降低。与别嘌醇相比，非布司他预处理显著调节了这些变化。预处理组的肠黏膜、肝和肺组织的病理损伤程度较轻。
非布司他在减轻小肠缺血/再灌注引起的局部肠道损伤以及远处肝和肺损伤方面可能优于别嘌醇。
