Adelmidrol ameliorates liver ischemia-reperfusion injury through activating Nrf2 signaling pathway

  • Eur J Pharmacol. 2023 Dec 16:176224. doi: 10.1016/j.ejphar.2023.176224.
Min Wu  1 ,  Xudong Liu  1 ,  Qiwen Yu  1 ,  Jihua Shi  1 ,  Wenzhi Guo  1 ,  Shuijun Zhang  2
Affiliations
  • 1. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Province, Zhengzhou, Henan, China; Zhengzhou Key Laboratory of Organ Transplantation Technology and Application Engineering, Zhengzhou, Henan, China.
  • 2. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China; Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Province, Zhengzhou, Henan, China; Zhengzhou Key Laboratory of Organ Transplantation Technology and Application Engineering, Zhengzhou, Henan, China. Electronic address: [email protected].
PMID: 38110141 DOI: 10.1016/j.ejphar.2023.176224
Abstract

Liver ischemia/reperfusion (I/R) injury commonly occurs after various liver surgeries. Adelmidrol, an N- palmitoylethanolamide analog, has anti-inflammatory, anti-oxidant, and anti-injury properties. To investigate whether adelmidrol could reduce liver I/R injury, we established a mouse of liver I/R injury and an AML12 cell hypoxia-reoxygenation model to perform experiments using multiple indicators. Serum ALT and AST levels, and H&E staining were used to measure liver damage; MDA content, superoxide dismutase and glutathione activities, and dihydroethidium staining were used to measure oxidative stress; mRNA expression levels of tumor necrosis factor-α, interleukin(IL)-1β, IL-6, MCP-1, and Ly6G staining were used to measure inflammatory response; and protein expression of Bax, Bcl-2, C-caspase3, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining were used to measure Apoptosis. The experimental results showed that adelmidrol reduced liver I/R injury. In addition, adelmidrol pretreatment elevated AML12 cell activity and reduced I/R-and H/R-induced Apoptosis, inflammatory injury, and oxidative stress. ML385, an inhibitor of nuclear factor erythroid2-related factor 2 (Nrf2), reverses liver I/R injury attenuated by adelmidrol. These results suggest that adelmidrol ameliorates liver I/R injury by activating the Nrf2 signaling pathway.

Keywords
Adelmidrol; Apoptosis; Inflammation; Liver ischemia/reperfusion; Nrf2; Oxidative stress.
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