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PTEN/PI3K/VEGF signaling pathway involved in the protective effect of xanthine oxidase inhibitor febuxostat against endometrial hyperplasia in rats.
Hum Exp Toxicol. 2020 Sep; 39(9):1224-1234.HE

Abstract

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) 2 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.

Authors+Show Affiliations

Department of Pharmacology, Faculty of Medicine, Minia University, Minia, Egypt.Department of Biochemistry, Faculty of Medicine, Minia University, Minia, Egypt.Department of Obstetrics and Gynecology, Faculty of Medicine, Al-Azhar University, Assuit, Egypt.Department of Histology, Faculty of Medicine, Minia University, Minia, Egypt.Department of Pharmacology, Faculty of Medicine, Minia University, Minia, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32228192

Citation

Mohamed, M Z., et al. "PTEN/PI3K/VEGF Signaling Pathway Involved in the Protective Effect of Xanthine Oxidase Inhibitor Febuxostat Against Endometrial Hyperplasia in Rats." Human & Experimental Toxicology, vol. 39, no. 9, 2020, pp. 1224-1234.
Mohamed MZ, Baky MAE, Hassan OA, et al. PTEN/PI3K/VEGF signaling pathway involved in the protective effect of xanthine oxidase inhibitor febuxostat against endometrial hyperplasia in rats. Hum Exp Toxicol. 2020;39(9):1224-1234.
Mohamed, M. Z., Baky, M. A. E., Hassan, O. A., Mohammed, H. H., & Abdel-Aziz, A. M. (2020). PTEN/PI3K/VEGF signaling pathway involved in the protective effect of xanthine oxidase inhibitor febuxostat against endometrial hyperplasia in rats. Human & Experimental Toxicology, 39(9), 1224-1234. https://doi.org/10.1177/0960327120914977
Mohamed MZ, et al. PTEN/PI3K/VEGF Signaling Pathway Involved in the Protective Effect of Xanthine Oxidase Inhibitor Febuxostat Against Endometrial Hyperplasia in Rats. Hum Exp Toxicol. 2020;39(9):1224-1234. PubMed PMID: 32228192.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PTEN/PI3K/VEGF signaling pathway involved in the protective effect of xanthine oxidase inhibitor febuxostat against endometrial hyperplasia in rats. AU - Mohamed,M Z, AU - Baky,Mf Abed El, AU - Hassan,O A, AU - Mohammed,H H, AU - Abdel-Aziz,A M, Y1 - 2020/03/31/ PY - 2020/4/2/pubmed PY - 2021/3/17/medline PY - 2020/4/2/entrez KW - Endometrial hyperplasia KW - febuxostat KW - phosphatase and tensin homolog KW - phosphatidylinositol-3-kinase KW - vascular endothelial growth factor SP - 1224 EP - 1234 JF - Human & experimental toxicology JO - Hum Exp Toxicol VL - 39 IS - 9 N2 - 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) 2 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. SN - 1477-0903 UR - https://www.unboundmedicine.com/medline/citation/32228192/PTEN/PI3K/VEGF_signaling_pathway_involved_in_the_protective_effect_of_xanthine_oxidase_inhibitor_febuxostat_against_endometrial_hyperplasia_in_rats_ DB - PRIME DP - Unbound Medicine ER -