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Updated: Mar 3, 2026
Ex Situ Normothermic Machine Perfusion of Donor Livers
Published on: May 26, 2015
Cross-Talk Between Sirtuin 1 and High-Mobility Box 1 in Steatotic Liver Graft Preservation
M A Zaouali1, A Panisello2, A Lopez3
1Experimental Hepatic Ischemia-Reperfusion Unit, Institut d'Investigacions Biomèdiques de Barcelona (IIBB), CSIC-IDIBAPS, Barcelona, Spain; Research Unit of Biology and Molecular Anthropology Applied to Development and Health (UR12ES11), Faculty of Pharmacy, University of Monastir, Tunisia; High Institut of Biotechnology of Monastir, University of Monastir, Tunisia.
Trimetazidine (TMZ) enhances liver graft preservation by increasing Sirtuin 1 (SIRT1) and autophagy in steatotic livers, reducing ischemia-reperfusion injury (IRI). This improves liver function and decreases inflammatory markers like HMGB1.
Area of Science:
- Hepatology
- Transplantation Biology
- Cellular Signaling
Background:
- Sirtuin 1 (SIRT1) is a key regulator in ischemia-reperfusion injury (IRI) pathways.
- High-mobility group box 1 protein (HMGB1) contributes to inflammation during IRI.
- The roles of SIRT1 and HMGB1 in liver preservation remain poorly understood.
Purpose of the Study:
- To investigate the relationship between SIRT1 and HMGB1 in steatotic and non-steatotic liver grafts.
- To evaluate the effect of trimetazidine (TMZ) on liver preservation using Institute Georges Lopez (IGL-1) solution.
- To assess the impact of TMZ on IRI markers and cellular pathways.
Main Methods:
- Steatotic and non-steatotic livers were preserved in IGL-1 solution with or without TMZ (10 μmol/L) for 24 hours at 4°C.
- Grafts underwent ex vivo reperfusion for 2 hours at 37°C.
- Liver injury, function, oxidative stress, mitochondrial damage, and expression of SIRT1, HMGB1, autophagy markers, PPAR-γ, and heat-shock proteins were assessed.
Main Results:
- TMZ-enriched IGL-1 solution increased SIRT1 and autophagy in steatotic livers post-reperfusion, unlike in non-steatotic livers.
- HO-1 expression increased in steatotic livers with TMZ, while HSP70 and PPAR-γ were enhanced in non-steatotic livers.
- TMZ treatment reduced liver injury, improved hepatic function, decreased TNF-α and HMGB1 levels, and prevented oxidative stress and mitochondrial damage.
Conclusions:
- SIRT1 is linked to HMGB1 reduction and enhanced autophagy in steatotic livers during cold preservation.
- TMZ-treated IGL-1 solution improves tolerance to cold ischemia-reperfusion injury in steatotic liver grafts.
- These findings highlight a potential therapeutic strategy for improving liver graft quality.
