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

Background. Selected esters of succinic acid were recently proposed as novel nutrients to support ATP generation in cells endangered by an i mbalance between the formation and breakdown of this adenine nucleotid e. In the present study, a new ester, glycerol-1,2,3-trimethylsuccinat e, 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 r at livers for 20 hr at 4 degrees C with a Belzer UW-CSS solution in th e absence or presence or 2 mM glycerol-1,2,3-trimethylsuccinate. Resul ts. Although it failed to affect significantly the release of cellular enzymes during storage and the protein or glycogen content of the liv er, and was unable to prevent the storage-induced decrease in both bio synthetic activity and D-[U-C-14]glucose incorporation into glycogen i n isolated hepatocytes, the ester restored to a close-to-normal value the viability of the hepatocytes and opposed the starvation-like effec ts of liver storage upon both the conversion of D-[U-C-14]glucose to ( CO2)-C-14 and radioactive amino acids and the de novo generation of C- 14-labeled D-glucose from [2-C-14]pyruvate. Conclusions. Because succi nic acid esters are efficiently metabolized in several cell types, the present results suggest that such esters may have a wide field of app lication in transplantation procedures.