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Air-ventilated normothermic machine perfusion alleviates hepatic injury from DCD rat through CYP1A2.
- Source :
-
Heliyon [Heliyon] 2023 Aug 19; Vol. 9 (8), pp. e19150. Date of Electronic Publication: 2023 Aug 19 (Print Publication: 2023). - Publication Year :
- 2023
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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.<br />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).<br />Results: M etabolomics 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.<br />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.<br />Competing Interests: The authors declare that there is no conflict of interest regarding the authorship and publication of this paper. All the authors have no interest with any financial business.<br /> (© 2023 Published by Elsevier Ltd.)
Details
- Language :
- English
- ISSN :
- 2405-8440
- Volume :
- 9
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Heliyon
- Publication Type :
- Academic Journal
- Accession number :
- 37654459
- Full Text :
- https://doi.org/10.1016/j.heliyon.2023.e19150