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Perindopril Ameliorates Hepatic Ischemia Reperfusion Injury Via Regulation of NF‐κB‐p65/TLR‐4, JAK1/STAT‐3, Nrf‐2, and PI3K/Akt/mTOR Signaling Pathways
Author(s) -
Kamel Esam O.,
Hassanein Emad H. M.,
Ahmed Marwa A.,
Ali Fares E. M.
Publication year - 2020
Publication title -
the anatomical record
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.678
H-Index - 62
eISSN - 1932-8494
pISSN - 1932-8486
DOI - 10.1002/ar.24292
Subject(s) - pi3k/akt/mtor pathway , malondialdehyde , oxidative stress , superoxide dismutase , protein kinase b , reperfusion injury , medicine , pharmacology , glutathione peroxidase , proinflammatory cytokine , tumor necrosis factor alpha , inflammation , endocrinology , chemistry , signal transduction , ischemia , biochemistry
Hepatic ischemia reperfusion (IR) is an inevitable clinical problem for surgical procedures such as liver transplantation and liver resection. This study was designed to evaluate the protective effect of perindopril (PER) against hepatic IR injury. Thirty‐two rats were used and randomly allocated into four groups. Sham control group was subjected to sham operation and received saline only, IR group was subjected to IR and received vehicle, PER group was pretreated with PER (one milligram per kilogram per day i.p. for 10 consecutive days), and IR+PER group was pretreated with PER then subjected to IR. Liver function biomarkers (aspartate aminotransferase and alanine aminotransferase), oxidative stress (glutathione, malondialdehyde, myeloperoxidase, and superoxide dismutase) and inflammation markers (tumor necrosis factor‐alpha, interferon‐gamma, and inteleukin‐10 [IL‐10]), mRNA expression of NF‐κB‐p65 and TLR‐4, as well as protein expression of JAK1, STAT‐3, PI3K, mTOR, Akt, and Nrf‐2 were investigated concomitantly with histopathological examination. The results indicated that, hepatic IR induced a significant alteration in liver function biomarkers and structure, oxidative stress, and inflammation. At the molecular level, up‐regulation of NF‐κB‐p65, TLR‐4, JAK1, and STAT‐3 concomitantly with down‐regulation of Nrf‐2, IL‐10, PI3K, Akt, and mTOR were observed. These disturbances were alleviated by pretreatment of IR rats with PER in concomitant with hepatic structural improvement. Conclusively, the protective effect of PER presumably may be relevant to its ability to reduce oxidative stress, ameliorate the inflammatory processes, and modify the related signaling pathways. Anat Rec, 2019. © 2019 American Association for Anatomy Anat Rec, 303:1935–1949, 2020. © 2019 American Association for Anatomy