Original scientific paper
https://doi.org/10.18054/pb.v127i3-4.35802
AGK2 pre-treatment mitigates hepatic ischemia-reperfusion injury by modulating sirtuin 2 expression and reducing inflammation and apoptosis
Yinqian He
; Department of Neurological Rehabilitation, Xi'an International Medical Center Hospital, Xi'an, Shaanxi, China
Wei Liu
; Department of Liver Disease, Yantai Qishan Hospital, Yantai, Shandong, China
Yan Zhang
; Department of Neurological Rehabilitation, Xi'an International Medical Center Hospital, Xi'an, Shaanxi, China
*
* Corresponding author.
Abstract
Ischemia-reperfusion injury (IRI) significantly impacts liver surgeries and transplantation due to oxidative stress, inflammation, and apoptosis. This study examines the protective effects of 2-cyano-3-[5-(2,5-dichlorophenyl)- 2-furanyl]-N-5-quinolinyl-2-propenamide (AGK2), a Sirtuin 2 (SIRT2) inhibitor, in hepatic IRI using in vitro and in vivo models. In vitro, HepG2 cells underwent hypoxia (1% oxygen for 45 minutes) followed by reoxygenation (21% oxygen for 2 hours) to simulate IRI. AGK2 was administered either 30 minutes before hypoxia (pre-treatment) or immediately after reoxygenation (post-treatment). Western blot analysis showed that IRI reduced SIRT2 expression to 50–60% of baseline levels, while AGK2 pre-treatment restored it to 130–150%, and post-treatment to 110–120%. Pre-treatment significantly reduced NF-κB activation and cleaved Caspase-3 levels, correlating with improved cell viability, as assessed by MTT assay. In vivo, a murine model of hepatic IRI (45 minutes ischemia, 2 hours reperfusion) was used, with AGK2 (20 mg/kg) administered pre- or post-treatment. IRI reduced hepatic SIRT2 expression to 50–60% of baseline, while AGK2 pre-treatment elevated it to 140–160%, and post-treatment to 110–130%. AGK2 pre-treatment significantly decreased NF-κB activation and cleaved Caspase-3 levels in liver tissues, indicating reduced inflammation and apoptosis. These findings suggest that AGK2 protects against hepatic IRI by modulating SIRT2 expression and attenuating inflammatory and apoptotic pathways. Pre-treatment consistently demonstrated superior efficacy compared to post-treatment, highlighting the importance of administration timing. This study supports the potential therapeutic application of AGK2 in mitigating hepatic ischemia-reperfusion injury.
Keywords
AGK2; SIRT2; ischemia-reperfusion injury; NF-kB; Caspase-3
Hrčak ID:
347135
URI
Publication date:
13.5.2026.
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