ACCELERATION OF HEPATOCELLULAR ENERGY BY IDEBENONE DURING EARLY REPERFUSION AFTER COLD PRESERVATION AMELIORATES HEAT-SHOCK-PROTEIN-70 GENE-EXPRESSION IN A PIG-LIVER MODEL

Background. Heat shock proteins (HSPs) are induced in the liver after warm ischemia/reperfusion and are thought to be markers of hepatocellu lar injury and oxidative stress. Methods. The influence of variable pe riods of cold storage followed by reperfusion on the expression of HSP 70 was studied in the isolated perfused pig liver, Organs were harvest ed and stored in histidine-tryptophan-ketoglutarate solution at 4 degr ees C and then perfused (210 min) in a closed water bath (38 degrees C ), which subjects the liver to fluctuating outer pressure. The role of energy depletion, reactive oxygen intermediates, Kupffer cells, and c irculating leukocytes in HSP70 expression was determined. Results. HSP 70 expression was not detectable in liver tissue before explantation o r before reperfusion by Northern blot analysis using a pig HSP70 gene probe, HSP70 expression was observed after reperfusion depending on co ld storage time, Kinetics of HSP70 expression monitored by reverse tra nscriptase polymerase chain reaction showed a rapid increase of mRNA w ithin 1 hr, which was closely associated with delayed recovery of hepa tocellular energy charge, as assessed by the ketone body ratio, The in activation of Kupffer cells, the presence or absence of leukocytes, an d the suppression of oxidative stress with the antioxidant idebenone, given during reperfusion, had no influence, However, feeding the anima ls with idebenone over 7 days before explantation led to a faster reco very of ketone body ratio, paralleled by a substantial suppression of HSP70 expression. Conclusions. Our data show that HSP70 expression dur ing reperfusion is mainly dependent on the preceding cold storage time and the consecutive delayed recovery of the hepatocellular energy cha rge.