Exogenous Phosphatidylserine Protects Against Mesenteric Ischemia-Reperfusion With Associated Akt/Mtor Pathway Upregulation Publisher Pubmed



Hamaneh AM ; Ghasemi M ; Mehrabi MM ; Ashtari S ; Nejati F ; Kazemzadeh H ; Goudarzi R ; Tavangar SM ; Dehpour AR ; Partoazar A
Source: Scientific Reports Published:2025

Abstract

Acute mesenteric ischemia–reperfusion is a life-threatening condition that causes severe intestinal injury through oxidative stress, inflammation, and apoptosis. Despite its high mortality rate, no pharmacological treatment is currently available to reduce tissue damage. This study aimed to evaluate the therapeutic potential of phosphatidylserine in a rat model of mesenteric ischemia–reperfusion and to explore its underlying mechanisms, with particular focus on the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. Thirty-six male Wistar rats were randomly assigned into six groups: sham, ischemia–reperfusion, and phosphatidylserine-treated groups at doses of 10, 20, and 40 mg/kg. Ischemia was induced by clamping the superior mesenteric artery for 60 min, followed by 60 min of reperfusion. Phosphatidylserine or vehicle was administered intraperitoneally 15 min before reperfusion. Ileal tissues were collected for histopathological evaluation, measurement of malondialdehyde, interleukin-6, glutathione peroxidase and superoxide dismutase activity, analysis of tumor necrosis factor-alpha, BAX, B-cell lymphoma 2, and assessment of Akt and mTOR phosphorylation by western blot. Reverse and molecular docking studies were conducted to identify potential targets of phosphatidylserine. Phosphatidylserine at 40 mg/kg significantly improved intestinal injury and modulated oxidative, inflammatory, and apoptotic markers. The findings support involvement of Akt/mTOR pathway and suggest phosphatidylserine as a potential therapeutic candidate. © 2025 Elsevier B.V., All rights reserved.