Glucose and fatty acid metabolism involved in the protective effect of metformin against ulipristal-induced endometrial changes in rats

Abstract Ulipristal acetate (UPA) is effective in the treatment of uterine fibroids. However, its clinical use is hampered by the development of pathologic progesterone receptor modulator-associated endometrial changes (PAECs). The current study was designed to test the hypothesis that UPA-induced P...

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Autores principales:	Marwa S. Hamza, Eman Ramadan, Salama A. Salama
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b2b11d58600c4498b139579ab2d2358b
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spelling	oai:doaj.org-article:b2b11d58600c4498b139579ab2d2358b2021-12-02T16:45:39ZGlucose and fatty acid metabolism involved in the protective effect of metformin against ulipristal-induced endometrial changes in rats10.1038/s41598-021-88346-w2045-2322https://doaj.org/article/b2b11d58600c4498b139579ab2d2358b2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88346-whttps://doaj.org/toc/2045-2322Abstract Ulipristal acetate (UPA) is effective in the treatment of uterine fibroids. However, its clinical use is hampered by the development of pathologic progesterone receptor modulator-associated endometrial changes (PAECs). The current study was designed to test the hypothesis that UPA-induced PAECs are associated with deranged expression of some metabolic genes. In addition, metformin can mitigate UPA-induced PAECs through modulating the expression of these genes. In the present study, twenty-eight female non-pregnant, nulligravid Wistar rats were treated with UPA (0.1 mg/kg/day, intragastric) and/or metformin (50 mg/kg/day, intragastric) for 8 weeks. Our results demonstrated that co-treatment with metformin significantly reduced UPA-induced PAECs. In addition, co-treatment with metformin and UPA was associated with significant increase in the Bax and significant reduction in Bcl-2, PCNA, Cyclin-D1and ER-α as compared to treatment with UPA alone. Furthermore, treatment with UPA alone was associated with deranged expression of 3-phosphoglycerate dehydrogenase (3-PHGDH), glucose-6-phosphate dehydrogenase (G6PD), transketolase (TKT), fatty acid synthase (FAS) and CD36. Most importantly, co-treatment with metformin markedly reduced UPA-induced altered expression of these metabolic genes in endometrial tissues. In conclusion, UPA-induced PAECs are associated with altered expression of genes involved in cell proliferation, apoptosis, estrogen receptor, glucose metabolism and lipid metabolism. Co-treatment with metformin abrogated UPA-induced PAECs most likely through the modulation of the expression of these genes.Marwa S. HamzaEman RamadanSalama A. SalamaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marwa S. Hamza Eman Ramadan Salama A. Salama Glucose and fatty acid metabolism involved in the protective effect of metformin against ulipristal-induced endometrial changes in rats
description	Abstract Ulipristal acetate (UPA) is effective in the treatment of uterine fibroids. However, its clinical use is hampered by the development of pathologic progesterone receptor modulator-associated endometrial changes (PAECs). The current study was designed to test the hypothesis that UPA-induced PAECs are associated with deranged expression of some metabolic genes. In addition, metformin can mitigate UPA-induced PAECs through modulating the expression of these genes. In the present study, twenty-eight female non-pregnant, nulligravid Wistar rats were treated with UPA (0.1 mg/kg/day, intragastric) and/or metformin (50 mg/kg/day, intragastric) for 8 weeks. Our results demonstrated that co-treatment with metformin significantly reduced UPA-induced PAECs. In addition, co-treatment with metformin and UPA was associated with significant increase in the Bax and significant reduction in Bcl-2, PCNA, Cyclin-D1and ER-α as compared to treatment with UPA alone. Furthermore, treatment with UPA alone was associated with deranged expression of 3-phosphoglycerate dehydrogenase (3-PHGDH), glucose-6-phosphate dehydrogenase (G6PD), transketolase (TKT), fatty acid synthase (FAS) and CD36. Most importantly, co-treatment with metformin markedly reduced UPA-induced altered expression of these metabolic genes in endometrial tissues. In conclusion, UPA-induced PAECs are associated with altered expression of genes involved in cell proliferation, apoptosis, estrogen receptor, glucose metabolism and lipid metabolism. Co-treatment with metformin abrogated UPA-induced PAECs most likely through the modulation of the expression of these genes.
format	article
author	Marwa S. Hamza Eman Ramadan Salama A. Salama
author_facet	Marwa S. Hamza Eman Ramadan Salama A. Salama
author_sort	Marwa S. Hamza
title	Glucose and fatty acid metabolism involved in the protective effect of metformin against ulipristal-induced endometrial changes in rats
title_short	Glucose and fatty acid metabolism involved in the protective effect of metformin against ulipristal-induced endometrial changes in rats
title_full	Glucose and fatty acid metabolism involved in the protective effect of metformin against ulipristal-induced endometrial changes in rats
title_fullStr	Glucose and fatty acid metabolism involved in the protective effect of metformin against ulipristal-induced endometrial changes in rats
title_full_unstemmed	Glucose and fatty acid metabolism involved in the protective effect of metformin against ulipristal-induced endometrial changes in rats
title_sort	glucose and fatty acid metabolism involved in the protective effect of metformin against ulipristal-induced endometrial changes in rats
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b2b11d58600c4498b139579ab2d2358b
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Glucose and fatty acid metabolism involved in the protective effect of metformin against ulipristal-induced endometrial changes in rats

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