Air-ventilated normothermic machine perfusion alleviates hepatic injury from DCD rat through CYP1A2

  • Heliyon. 2023 Aug 19;9(8):e19150. doi: 10.1016/j.heliyon.2023.e19150.
Ji-Hua Shi  1 ,  Nuo Cheng  1 ,  Wen Zhang  1 ,  Qiang Jin  2 ,  Wen-Zhi Guo  1 ,  Guang-Bo Ge  2 ,  Shui-Jun Zhang  1 ,  Pål-Dag Line  3 ,  Yong Wang  4
Affiliations
  • 1. Department of Hepatobiliary and Pancreatic Surgery, Henan Key Laboratory of Digestive Organ Transplantation & Zhengzhou Key Laboratory for HPB Diseases and Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
  • 2. Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 200473, China.
  • 3. Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • 4. Department of Anesthesia Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
PMID: 37654459 DOI: 10.1016/j.heliyon.2023.e19150
Abstract

Background: Normothermic machine perfusion (NMP) could provide protection to organs from donation after circulatory death (DCD) before transplantation, and its molecular mechanism remains unclear. Our previous study discovered that the air-ventilated NMP confers a better DCD liver recovery than oxygen-ventilated NMP. The purpose in the current study was to investigate the protective mechanism of air-ventilated NMP in a rat model of DCD liver by metabolomics, and to select biomarker to predict liver function recovery.

Materials and methods: Peroxisome proliferator activator receptor-α (PPARα) agonist or antagonist was administered via the perfusion circuit in the air-ventilated NMP. Perfusate samples were taken for measurements of aminotransferases using standard biochemical methods, tumor necrosis factor-alpha and interleukin-6. Liver biopsies were allocated for detection of metabolomics, PPARα and Cytochrome P450 1A2 (CYP1A2).

Results: Metabolomics analysis revealed the significant increased γ-linolenic acid and decreased adrenic acid during the air-ventilated NMP, indicating linoleic acid metabolism pathway was associated with a better DCD liver recovery; as a major enzyme involved in linolenic acid metabolism, CYP1A2 was found correlated with a less inflammation and better liver function with the air-ventilated NMP; PPARα Agonist could increase CYP1A2 expression and activity, decrease inflammation response, and improve liver function with the air-ventilated NMP, while PPARα Antagonist played the opposite.

Conclusion: Air-ventilated NMP confers a better liver recovery from DCD rats through the activated linoleic acid metabolism and CYP1A2 upregulation; CYP1A2 expression and activity might function as biomarker to predict DCD liver function recovery with NMP.

Keywords
Cytochrome P450 1A2; Donation after circulatory death; Normothermic machine perfusion; Peroxisome proliferator activator receptor-α.
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