Perindopril ameliorates hepatic IR injury via regulation of NF- κB-p65/TLR-4, JAK1/STAT-3, Nrf-2 and PI3K/Akt/mTOR signaling pathways.

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 (1 mg/kg/day i.p. for 10 consecutive days) and IR+PER group was pretreated with PER then subjected to IR. Liver function biomarkers (AST and ALT), oxidative stress (GSH, MDA, MPO and SOD) and inflammation markers (TNF-α, INF-γ and 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 pre-treatment 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. This article is protected by copyright. All rights reserved. PMID: 31606943 [PubMed - as supplied by pu...
Source: Anatomical Record - Category: Anatomy Authors: Tags: Anat Rec (Hoboken) Source Type: research