Background and aim: In order to reduce mortality on waiting list, therapeutic strategies are required to increase the use of steatotic liver grafts in transplantation. However, steatotic grafts tolerate poorly ischemia-reperfusion (I/R) injury, and therefore they show a very high risk to early allograft dysfunction or primary nonfunction after transplantation. The aim of the present research was to evaluate the potential of 3 pharmacological modulators of lipid metabolism to induce defatting and protection against hepatic damage during cold preservation period in steatotic liver grafts.
Material and methods: Wistar rats were fed with a high-fat diet to induce steatosis. Then, steatotic livers were preserved at 4° C for 6hours, either in Custodiol preservation solution, or in Custodiol solution enriched with caffeine, choline, or l-carnitine. At the end of this period, grafts were washed-out and transaminases and triglycerides in liver tissue were determined. This study was approved by the institutional Research Ethics Committee.
Results: Addition of caffeine to Custodiol solution decreased hepatic triglycerides content by 56% in steatotic grafts when compared with grafts preserved only in Custodiol. Triglycerides content was similar in steatotic grafts preserved in Custodiol enriched with choline or l-carnitine, and in those grafts preserved in Custodiol without additives. Regarding liver injury, preservation in Custodiol supplemented with caffeine, choline or l-carnitine resulted in a decrease in transaminases, compared to the levels observed in preservation with solely Custodiol.
Conclusions: Addition of caffeine to preservation solution trigger defatting in steatotic liver grafts, which is associated with protection against I/R injury. The enrichment of preservation solution with choline or l-carnitine decrease I/R injury in steatotic grafts, but this effect was not related to reduction in triglyceride content.
This work has been fully funded by the Fondo Sectorial de Investigación para la Educación from CONACYT (PI 257743).
Conflicts of interest: The authors have no conflicts of interest to declare.
