{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:53:59Z","timestamp":1785430439711,"version":"3.56.0"},"reference-count":69,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006701","name":"Umm Al-Qura University, Saudi Arabia","doi-asserted-by":"publisher","award":["26UQU4310007GSSR03"],"award-info":[{"award-number":["26UQU4310007GSSR03"]}],"id":[{"id":"10.13039\/501100006701","id-type":"DOI","asserted-by":"publisher"}]},{"award":["26UQU4310007GSSR03"],"award-info":[{"award-number":["26UQU4310007GSSR03"]}],"id":[{"id":"https:\/\/ror.org\/01xjqrm90","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Juvenile intestinal ischemia\u2013reperfusion (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\u20134 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-\u03baB), 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.<\/jats:p>","DOI":"10.3390\/ijms27125370","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T08:57:58Z","timestamp":1781513878000},"page":"5370","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting PI3K\/Akt\/mTOR Pathway, Ki-67 and Endothelin Receptors by Ambrisentan in Juvenile Rat Intestinal Ischemia"],"prefix":"10.3390","volume":"27","author":[{"given":"Marwa Monier Mahmoud","family":"Refaie","sequence":"first","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine, Minia University, Minia 61511, Egypt"},{"name":"Faculty of Medicine, Minia National University, New Minia 61768, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanaa Hassanein","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Minia National University, New Minia 61768, Egypt"},{"name":"Department of Histology and Cell Biology, Faculty of Medicine, Minia University, Minia 61511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3787-1823","authenticated-orcid":false,"given":"Asmaa A.","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy and Embryology, Faculty of Medicine, Aswan University, Aswan 81528, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayed","family":"Shehata","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Faculty of Medicine, Minia University, Minia 61511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5998-9739","authenticated-orcid":false,"given":"Asmaa","family":"A. Muhammed","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Faculty of Medicine, Aswan University, Aswan 81528, Egypt"},{"name":"Department of Physiology, RAK College of Medical Sciences, RAK Medical & Health Sciences University, Ras-AlKhaimah 11127, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3886-2925","authenticated-orcid":false,"given":"Mohamad Assayed","family":"Nader","sequence":"additional","affiliation":[{"name":"Pediatric Surgery Unit, General Surgery Department, Faculty of Medicine, Aswan University, Aswan 81528, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zamzam M.","family":"Abdelsamie","sequence":"additional","affiliation":[{"name":"Department of Pediatric, Faculty of Medicine, Aswan University, Aswan 81528, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoda S.","family":"Sherkawy","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Aswan University, Aswan 81528, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enas","family":"Fathy","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Faculty of Medicine, Aswan University, Aswan 81528, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shereen Mohammed Mohammed","family":"Elsaghir","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, Minia University, Minia 61511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma F.","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Molecular biology and Physiology, Faculty of Medicine, Mutah University, Al-Karak 61101, Jordan"},{"name":"Department of Medical Physiology, Faculty of Medicine, Minia University, Minia 61511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2118-0499","authenticated-orcid":false,"given":"Ahmed M.","family":"Ashour","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Khames","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6790-496X","authenticated-orcid":false,"given":"Doaa","family":"Mohamed Elroby Ali","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt"},{"name":"Department of Biochemistry, Faculty of Pharmacy, Badr University Branch Assiut, Assiut 71511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e70136","DOI":"10.1002\/ctm2.70136","article-title":"Intestinal oxygen utilisation and cellular adaptation during intestinal ischaemia-reperfusion injury","volume":"15","author":"Mavridis","year":"2025","journal-title":"Clin. 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