Título

INSTITUT GEORGES LOPEZ- 1 SOLUTION PREVENTS FROM PROTEASOME ACTIVATION IN FATTY LIVER PRESERVATION.

Introdução

We have recently demonstrated that the inhibition of ubiquitin proteasome system (UPS) protects fatty liver grafts against cold ischemic-reperfusion injury. The aim of this study was to investigate the effect of two different preservation solutions Institut George Lopez (IGL-1) and Histidine Tryptophan-Ketoglutarate (HTK) on UPS when liver grafts were subjected to 24h-cold ischemic preservation.

Material e Método

Steatotic livers from obese Zücker rats were preserved for 24 h (at 4 °C) in IGL-1 or in HTK solutions. Liver injury (AST/ALT) and ATP decreases, proteasome chymotrysin like ATP-dependent (26S) and ATP-independent (20S) activity were assessed.

Resultados

Livers preserved in IGL-1 showed lesser liver injury (AST/ALT) when compared to HTK. This was consistent with an increased preservation of ATP levels which was concomitant with diminution of chymotrypsin-like activity of 26S and 20S proteasome subunits, respectively. These results were corroborated by the histological findings. A significant diminution in polyubiquitinated proteins levels was also observed when compared to HTK

Discussão e Conclusões

Data reported here showed that the prevention of proteasome activation could be modulated by the organ preservation solution during graft cold storage being this fact determinant for the prevention of cold ischemia injury during graft preservation. The presence of oncotic agent , PEG35, in IGL-1 seems determinant for the inhibitory action on UPS during cold graft preservation in constrast to HTK (no oncotic agent)

In conclusion, IGL-1 solution preserved better fatty liver grafts (24 h; 4ºC) than HTK solution after a long period of cold storage by the inhibitory action on proteasome activity during cold preservation.

Palavras Chave

Fatty liver grafts preservation, cold ischemic injury, IGL-1, HTK, ubiquitin proteasome