Optimizing DCD donor liver function with resveratrol during machine perfusion

Extensive research has explored the use of machine perfusion to repair liver grafts, among these, interventions targeting mitochondrial repair are gaining attention due to its central role in ischemia-reperfusion injury and graft viability. Resveratrol, a mild natural polyphenol, is investigated here as a representative compound. Rat donor livers were subjected to 30 min of asystolic warm ischemia (DCD), followed by 2 h of either static cold storage (SCS), subnormothermic machine perfusion (SNMP) at 25 °C, or SNMP supplemented with resveratrol (SNMP-RES). All livers were subsequently reperfused under normothermic conditions for 1 h (NMP) with donor blood. Biochemical, transcriptomics RNA sequencing, inflammatory, and histological analyses were performed on perfusate samples and liver tissue biopsies. Resveratrol significantly enhanced the protective effects of SNMP, reducing perfusate AST (p = 0.03) and flavin mononucleotide (FMN) (p = 0.01). Resveratrol also decreased perfusate cytokine levels and improved tissue morphology. Transcriptomic analysis identified an upregulation of regenerative pathways using resveratrol, including Notch-signaling and Wnt signaling. The innate immune response was downregulated. This study represents the potential of FMN as a marker for liver quality during SNMP for the first time and demonstrates resveratrol's effects during SNMP. These findings encourage further exploration of mitochondrial-targeted preservation strategies and validate long-term benefits.