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PTEN/PI3K/VEGF signaling pathway involved in the protective effect of xanthine oxidase inhibitor febuxostat against endometrial hyperplasia in rats.
Human & Experimental Toxicology ( IF 2.7 ) Pub Date : 2020-03-31 , DOI: 10.1177/0960327120914977
M Z Mohamed 1 , Mf Abed El Baky 2 , O A Hassan 3 , H H Mohammed 4 , A M Abdel-Aziz 1
Affiliation  

Endometrial hyperplasia (EH) is a medical condition that affects many females as it increases their uterine carcinogenic potential. EH results from entangling hormonal imbalance and inflammatory response. The study examined the role of a xanthine oxidase inhibitor, febuxostat, in a rat model of EH. Adult female Wistar albino rats were subjected to estradiol valerate (EV) 20 mg/kg for 10 days to induce EH. Another group was treated concomitantly with febuxostat 10 mg/kg for the same period. The uterine malondialdehyde, reduced glutathione (GSH), and superoxide dismutase (SOD) were assessed by chemical methods. Gene expressions of phosphatidylinositol-3-kinase (PI3K), Akt, and hypoxia-inducible factor 1 alpha were assessed by the quantitative real-time polymerase chain reaction. Moreover, the vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay. Histopathology and immunohistochemical techniques were used for the detection of phosphatase and tensin homolog (PTEN). The results revealed that EV administration induced complex EH with focal atypia and loss of PTEN expression by the histological examination. Uteri of the EV group showed a significant drop in GSH content and SOD activity and rise in the expressions of PI3K, Akt, VEGF, and IL-6. Febuxostat administration significantly improved the uterine GSH and SOD levels. It decreased the expressions of PI3K, Akt, VEGF, and IL-6. The endometrium showed a regression of the proliferative epithelium with the restoration of PTEN expression and the absence of the atypical features. In conclusion, febuxostat protected the endometrium against estrogen-induced EH and may be beneficial in the management along with the hormonal therapy.



中文翻译:

PTEN / PI3K / VEGF信号通路参与黄嘌呤氧化酶抑制剂非布司他对大鼠子宫内膜增生的保护作用。

子宫内膜增生(EH)是一种医学疾病,会影响许多女性,因为它们会增加子宫致癌的潜力。EH是由纠缠的荷尔蒙失调和炎症反应引起的。这项研究检查了黄嘌呤氧化酶抑制剂非布索坦在EH大鼠模型中的作用。成年雌性Wistar白化病大鼠接受20 mg / kg戊酸雌二醇(EV)作用10天,以诱导EH。另一组在同期接受非布索坦10 mg / kg的同时治疗。通过化学方法评估子宫丙二醛,还原型谷胱甘肽(GSH)和超氧化物歧化酶(SOD)。通过定量实时聚合酶链反应评估磷脂酰肌醇3-激酶(PI3K),Akt和缺氧诱导因子1α的基因表达。此外,酶联免疫吸附法测定血管内皮生长因子(VEGF)和白细胞介素6(IL-6)。使用组织病理学和免疫组化技术检测磷酸酶和张力蛋白同源物(PTEN)。结果表明,通过组织学检查,EV给药可诱发具有局灶性非典型性的复杂EH和PTEN表达的丧失。EV组的子宫显示GSH含量和SOD活性显着下降,PI3K,Akt,VEGF和IL-6的表达上升。非布索坦给药显着改善了子宫GSH和SOD水平。它降低了PI3K,Akt,VEGF和IL-6的表达。子宫内膜显示出增殖性上皮的消退,PTEN表达得以恢复并且缺乏非典型特征。结论,

更新日期:2020-04-20
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