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Updated: Jun 27, 2026
Rat Mesentery Angiogenesis Assay
Published on: June 18, 2011
Targeting PI3K/Akt/mTOR Pathway, Ki-67 and Endothelin Receptors by Ambrisentan in Juvenile Rat Intestinal Ischemia
Marwa Monier Mahmoud Refaie1,2, Hanaa Hassanein Mohammed2,3, Asmaa A Hasan4
1Department of Medical Pharmacology, Faculty of Medicine, Minia University, Minia 61511, Egypt.
Insights
Juvenile intestinal ischemia-reperfusion (JII/R) is a serious condition affecting young patients. Ambrisentan (AMB) shows promise in reducing cardiac and intestinal damage in a rat model of JII/R.
Area of Science:
- Pediatric Surgery
- Gastroenterology
- Cardiology
Background:
- Juvenile intestinal ischemia-reperfusion (JII/R) is a critical pediatric surgical emergency with high mortality.
- Malrotation-induced midgut volvulus can lead to intestinal ischemia and affect cardiac tissue.
- Effective therapeutic strategies for JII/R are urgently needed.
Purpose of the Study:
- To evaluate the therapeutic potential of ambrisentan (AMB) in a rat model of induced JII/R.
- To investigate the effects of AMB on cardiac enzymes, oxidative stress, inflammation, and apoptosis in JII/R.
- To assess the impact of AMB on histopathological changes in the intestine and cardiac tissue.
Main Methods:
- Induction of JII/R in juvenile male Wistar albino rats by superior mesenteric artery clamping.
- Administration of ambrisentan (30, 60 mg/kg) to JII/R rats.
- Assessment of cardiac enzymes, oxidative stress markers (MDA), inflammatory markers (NF-κB), apoptotic markers (caspase-3), endothelin receptor A (ERA) expression, and histopathological changes.
Main Results:
- JII/R induced significant cardiac enzyme elevation, oxidative stress, inflammation, apoptosis, and ERA expression.
- Histopathology showed severe mucosal damage, villi loss, cardiac fiber degeneration, and necrosis.
- Ambrisentan treatment significantly reduced cardiac enzymes, MDA, NF-κB, ERA, and caspase-3 levels.
- Ambrisentan increased PI3K, Akt, Ki-67, and mTOR expression, improving histopathological outcomes.
Conclusions:
- Ambrisentan demonstrates significant protective effects against JII/R-induced cardiac and intestinal injury in rats.
- AMB mitigates oxidative stress, inflammation, and apoptosis while promoting tissue repair pathways.
- Ambrisentan may serve as a valuable adjuvant therapy for juvenile intestinal ischemia-reperfusion.
Abstract:
Juvenile intestinal ischemia-reperfusion (JII/R) is a pediatric surgical emergency caused by mesenteric vessel occlusion and has a high mortality rate. Malrotation can cause intestinal ischemia in infants due to midgut volvulus. It affects not only the intestine itself but also other organs, such as cardiac tissue. Therefore, searching for more effective therapeutic solutions is an essential critical need. This directed our thoughts to evaluate the role of ambrisentan (AMB) in a rat model of induced JII/R by clamping the superior mesenteric artery. Forty juvenile male Wistar albino rats (3-4 weeks old) were randomly divided into four experimental groups: control (CON) group, JII/R group, and AMB-treated groups (30, 60 mg/kg) with JII/R. Induction of JII/R results in significant changes in cardiac enzymes, oxidative stress, inflammatory, and apoptotic parameters with high expression of endothelin receptor A (ERA). Also, histopathological changes revealed extensive mucosal damage, loss of intestinal villi, dysregulated and degenerated cardiac fibers with inflammatory cell infiltration, and tissue necrosis. In contrast, AMB administration significantly reduced the elevated levels of cardiac enzymes, malondialdehyde (MDA), nuclear factor kappa B (NF-κB), ERA, and caspase-3 expression. However, AMB treatment increased immune expressions of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), Ki-67, and mammalian target of rapamycin (mTOR) and showed remarkable improvement in the histopathological changes. AMB could be considered as an adjuvant medical treatment for cases of JII/R.
