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- W4232929799 abstract "Abstract Background : Hepatic ischemia-reperfusion injury (IRI) is a major unavoidable clinical problem often occurs during various liver surgery and transplantation. D-Pinitol, a cyclic polyol, showed its hepatoprotective efficacy in clinical and experimental settings. Aim : To determine the potential and possible mechanism of pinitol against ER stress regulation-mediated hepatic IRI in experimental rats. Materials and methods : Male SD rats were pre-treated with pinitol for 21 days and then subjected to 60 min. of partial hepatic ischemia followed by 24 h. of reperfusion. Various parameters were evaluated, including liver function tests, inflammatory release, endoplasmic reticulum (ER) stress, apoptosis, and structural modifications. Results : Pre-treatment with pinitol (10 and 20 mg/kg) effectively protected IRI-induced hepatic damage reflected by attenuation of elevated AST, ALT, oxidative stress (SOD, GSH, MDA and NO) and pro-inflammatory cytokines (TNF-α and IL’s) release. Interestingly, western blot and ELISA analysis suggested that pinitol significantly down-regulated the expression of ER stress apoptotic markers, namely GRP78, CHOP, AFT-4, AFT-6α, XBP-1, and caspase-3, 9 and 12. Additionally, pinitol pre-treatment improved mitochondrial function and phosphorylation of ERK1/2 and P38. Pinitol markedly protected IRI-induced hepatic apoptosis determined by flow cytometry. The hepatic histological and ultrastructural aberration induced by IRI was effectively protected by pinitol. Conclusion : Findings of the present investigation suggested that pinitol offered protection against ER stress-mediated phosphorylation of ERK1/2 and p38, thereby inhibited AFT4-CHOP/GRP78 signaling response and induction of caspase-3 induced hepatocellular apoptosis during hepatic ischemia-reperfusion insults." @default.
- W4232929799 created "2022-05-12" @default.
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- W4232929799 date "2021-04-27" @default.
- W4232929799 modified "2023-10-16" @default.
- W4232929799 title "D-Pinitol Protected Against Endoplasmic Reticulum Stress and Apoptosis in Hepatic Ischemia-Reperfusion Injury Via Modulation of AFT4-CHOP/GRP78 and Caspase-3 Signaling Pathways" @default.
- W4232929799 doi "https://doi.org/10.21203/rs.3.rs-436802/v1" @default.
- W4232929799 hasPublicationYear "2021" @default.
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