scholarly journals 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

2021 ◽  
Vol 14 (7) ◽  
pp. 649
Author(s):  
Mohamed A. Morsy ◽  
Wedad M. Abdelraheem ◽  
Maram El-Hussieny ◽  
Marwa M. M. Refaie

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.

Chemotherapy ◽  
2009 ◽  
Vol 55 (6) ◽  
pp. 399-406 ◽  
Author(s):  
Samira Saleh ◽  
Afaf A. Ain-Shoka ◽  
Ebtehal El-Demerdash ◽  
Marwa M. Khalef

2010 ◽  
Vol 160 (3) ◽  
pp. 487.e1-487.e7 ◽  
Author(s):  
Christian Cadeddu ◽  
Alessandra Piras ◽  
Giovanni Mantovani ◽  
Martino Deidda ◽  
Mariele Dessì ◽  
...  

Hypertension ◽  
2008 ◽  
Vol 52 (3) ◽  
pp. 563-572 ◽  
Author(s):  
Toshio Imanishi ◽  
Hiroto Tsujioka ◽  
Hideyuki Ikejima ◽  
Akio Kuroi ◽  
Shigeho Takarada ◽  
...  

We investigated whether aliskiren, a direct renin inhibitor, improves NO bioavailability and protects against spontaneous atherosclerotic changes. We also examined the effects of cotreatment with aliskiren and valsartan, an angiotensin II receptor blocker, on the above-mentioned outcomes. Watanabe heritable hyperlipidemic rabbits were treated with vehicle (control), aliskiren, valsartan, or aliskiren plus valsartan for 8 weeks. Then, acetylcholine-induced NO production was measured as a surrogate index of endothelium protective function, and both superoxide and vascular peroxynitrite were measured. Tetrahydrobiopterin in aortic segments was assessed by high-performance liquid chromatography with fluorescence detection. Plaque area was quantified by histology. Increase in plasma NO concentration in response to intra-aortic acetylcholine infusion was significantly greater in all of the test groups than in controls. Aliskiren+valsartan cotreatment increased acetylcholine-induced NO by 6.2 nmol/L, which was significantly higher than that with either aliskiren or valsartan alone. Vascular superoxide and peroxynitrite levels were both significantly higher in controls and significantly lower in the aliskiren+valsartan group than in the aliskiren or valsartan group. The highest tetrahydrobiopterin levels were observed after aliskiren+valsartan cotreatment. Histology of the thoracic aorta revealed that the plaque area was significantly decreased with combination therapy compared with monotherapy. Treatment with a direct renin inhibitor has protective effects on endothelial function and atherosclerotic changes. Furthermore, cotreatment with a direct renin inhibitor and an angiotensin II receptor blocker has additive protective effects on both.


PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e49642 ◽  
Author(s):  
Yasunori Iida ◽  
Baohui Xu ◽  
Geoffrey M. Schultz ◽  
Vinca Chow ◽  
Julie J. White ◽  
...  

2015 ◽  
Vol 148 (4) ◽  
pp. S-172 ◽  
Author(s):  
Vesta Valuckaite ◽  
Sarah Ruderman ◽  
Anas Almoghrabi ◽  
John Hart ◽  
Almaz Abdyrakov ◽  
...  

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