IMPROVED VIABILITY AND METABOLIC BEHAVIOR OF HEPATOCYTES AFTER LIVER STORAGE IN THE PRESENCE OF A SUCCINIC ACID ESTER1

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Abstract
Background. Selected esters of succinic acid were recently proposed as novel nutrients to support ATP generation in cells endangered by an imbalance between the formation and breakdown of this adenine nucleotide. In the present study, a new ester, glycerol-1,2,3-trimethylsuccinate, was examined for its potential beneficial effect in the procedures preceding liver transplantation. Methods. The viability and metabolic behavior of hepatocytes were examined after perfusion and storage of rat livers for 20 hr at 4°C with a Belzer UW-CSS solution in the absence or presence or 2 mM glycerol-1,2,3-trimethylsuccinate. Results. Although it failed to affect significantly the release of cellular enzymes during storage and the protein or glycogen content of the liver, and was unable to prevent the storage-induced decrease in both biosynthetic activity and D-[U-14C]glucose incorporation into glycogen in isolated hepatocytes, the ester restored to a close-to-normal value the viability of the hepatocytes and opposed the starvation-like effects of liver storage upon both the conversion of D-[U-14C]glucose to 14CO2 and radioactive amino acids and the de novo generation of14 C-labeled D-glucose from [2-14C]pyruvate. Conclusions. Because succinic acid esters are efficiently metabolized in several cell types, the present results suggest that such esters may have a wide field of application in transplantation procedures.