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Protective Effects of Irbesartan, an Angiotensin Receptor Blocker with PPARγ Agonistic Activity, against Estradiol Benzoate-Induced Endometrial Hyperplasia and Atypia in Female Rats via Modulation of TNFα/Survivin Pathway.
Pharmaceuticals (Basel). 2021 Jul 06; 14(7)P

Abstract

Endometrial hyperplasia (EH) is a common gynecological problem and may progress to carcinoma. Early detection and management of EH are mandatory for the prevention of endometrial cancer. Activation of the renin-angiotensin system and angiotensin II signaling are involved in the progression of precancerous and cancerous lesions. However, no studies have evaluated the role of this system in estradiol benzoate (EB)-induced EH and atypia. Irbesartan (IRB), an angiotensin II receptor blocker with peroxisome proliferator-activated receptor gamma (PPARγ) agonistic activity was administered (30 mg/kg/d) in EB-treated (60 µg/100 g bodyweight, intramuscularly, three times per week) or untreated rats for 4 weeks. Uterine weight changes, malondialdehyde, superoxide dismutase (SOD), tumor necrosis factor-alpha (TNFα), survivin, cleaved caspase 3, interleukin-10 (IL10), and PPARγ were measured in addition to undergoing histopathological examination. Results showed that EB-induced EH and atypia significantly increased the uterine body weight, malondialdehyde, TNFα, and survivin, accompanied with significantly decreased SOD, cleaved caspase 3, IL10, and PPARγ, with typical histopathological changes of EH and atypia. Coadministration of IRB significantly prevented EB-induced biochemical and histopathological changes. The protective effects of IRB may be attributed to its anti-inflammatory and antioxidant properties, reduction of survivin, and increased levels of cleaved caspase 3.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia. Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia 61511, Egypt.Department of Medical Microbiology and Immunology, Faculty of Medicine, Minia University, El-Minia 61511, Egypt.Department of Pathology, Faculty of Medicine, Minia University, El-Minia 61511, Egypt.Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia 61511, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34358075

Citation

Morsy, Mohamed A., et al. "Protective Effects of Irbesartan, an Angiotensin Receptor Blocker With PPARγ Agonistic Activity, Against Estradiol Benzoate-Induced Endometrial Hyperplasia and Atypia in Female Rats Via Modulation of TNFα/Survivin Pathway." Pharmaceuticals (Basel, Switzerland), vol. 14, no. 7, 2021.
Morsy MA, Abdelraheem WM, El-Hussieny M, et al. Protective Effects of Irbesartan, an Angiotensin Receptor Blocker with PPARγ Agonistic Activity, against Estradiol Benzoate-Induced Endometrial Hyperplasia and Atypia in Female Rats via Modulation of TNFα/Survivin Pathway. Pharmaceuticals (Basel). 2021;14(7).
Morsy, M. A., Abdelraheem, W. M., El-Hussieny, M., & Refaie, M. M. M. (2021). Protective Effects of Irbesartan, an Angiotensin Receptor Blocker with PPARγ Agonistic Activity, against Estradiol Benzoate-Induced Endometrial Hyperplasia and Atypia in Female Rats via Modulation of TNFα/Survivin Pathway. Pharmaceuticals (Basel, Switzerland), 14(7). https://doi.org/10.3390/ph14070649
Morsy MA, et al. Protective Effects of Irbesartan, an Angiotensin Receptor Blocker With PPARγ Agonistic Activity, Against Estradiol Benzoate-Induced Endometrial Hyperplasia and Atypia in Female Rats Via Modulation of TNFα/Survivin Pathway. Pharmaceuticals (Basel). 2021 Jul 6;14(7) PubMed PMID: 34358075.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective Effects of Irbesartan, an Angiotensin Receptor Blocker with PPARγ Agonistic Activity, against Estradiol Benzoate-Induced Endometrial Hyperplasia and Atypia in Female Rats via Modulation of TNFα/Survivin Pathway. AU - Morsy,Mohamed A, AU - Abdelraheem,Wedad M, AU - El-Hussieny,Maram, AU - Refaie,Marwa M M, Y1 - 2021/07/06/ PY - 2021/05/19/received PY - 2021/06/29/revised PY - 2021/07/01/accepted PY - 2021/8/6/entrez PY - 2021/8/7/pubmed PY - 2021/8/7/medline KW - cleaved caspase 3 KW - endometrial hyperplasia KW - estradiol benzoate KW - interleukin-10 KW - irbesartan KW - peroxisome proliferator-activated receptor gamma KW - survivin KW - tumor necrosis factor-alpha JF - Pharmaceuticals (Basel, Switzerland) JO - Pharmaceuticals (Basel) VL - 14 IS - 7 N2 - Endometrial hyperplasia (EH) is a common gynecological problem and may progress to carcinoma. Early detection and management of EH are mandatory for the prevention of endometrial cancer. Activation of the renin-angiotensin system and angiotensin II signaling are involved in the progression of precancerous and cancerous lesions. However, no studies have evaluated the role of this system in estradiol benzoate (EB)-induced EH and atypia. Irbesartan (IRB), an angiotensin II receptor blocker with peroxisome proliferator-activated receptor gamma (PPARγ) agonistic activity was administered (30 mg/kg/d) in EB-treated (60 µg/100 g bodyweight, intramuscularly, three times per week) or untreated rats for 4 weeks. Uterine weight changes, malondialdehyde, superoxide dismutase (SOD), tumor necrosis factor-alpha (TNFα), survivin, cleaved caspase 3, interleukin-10 (IL10), and PPARγ were measured in addition to undergoing histopathological examination. Results showed that EB-induced EH and atypia significantly increased the uterine body weight, malondialdehyde, TNFα, and survivin, accompanied with significantly decreased SOD, cleaved caspase 3, IL10, and PPARγ, with typical histopathological changes of EH and atypia. Coadministration of IRB significantly prevented EB-induced biochemical and histopathological changes. The protective effects of IRB may be attributed to its anti-inflammatory and antioxidant properties, reduction of survivin, and increased levels of cleaved caspase 3. SN - 1424-8247 UR - https://www.unboundmedicine.com/medline/citation/34358075/Protective_Effects_of_Irbesartan_an_Angiotensin_Receptor_Blocker_with_PPARγ_Agonistic_Activity_against_Estradiol_Benzoate_Induced_Endometrial_Hyperplasia_and_Atypia_in_Female_Rats_via_Modulation_of_TNFα/Survivin_Pathway_ L2 - https://www.mdpi.com/resolver?pii=ph14070649 DB - PRIME DP - Unbound Medicine ER -
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