Effects of geranyl-geranyl-acetone administration before heat shock preconditioning for conferring tolerance against ischemia-reperfusion injury in rat livers

The effect of geranyl-geranyl-acetone (GGA) administration before heat shoc k preconditioning on heat shock protein (HSP) 72 induction and on the acqui sition of tolerance against ischemia-reperfusion injury was studied in rat livers. Male Wistar rats were divided into four groups: a control group (gr oup C); a GGA group (group G); a simple heat shock group (group VH); and a heat shock with GGA premedication group (group GH), Five-, 10-, and 15-minu te periods of heat shock preconditioning at 42 degrees C were performed in groups VH and GH. Subgroups were determined according to the period of heat shock exposure. After a 48-hour recovery, rats in groups C, VH5, VH15, and GH5 received a 30-minute period of hepatic ischemia. Induction of HSP72, s urvival rates, and changes in biochemical and histologic parameters were co mpared among the groups. Five-minute heat shock preconditioning was not eno ugh to induce HSP72. However, livers in group GH5 expressed approximately t he same amount of HSP72 as those in group VH15. The expression of HSP72 in group GH15 was stronger than that found in group VH15. The degree and locat ion of HSP72 expression were not different between groups GH5 and VH15. Sev en-day survival was significantly better in groups GH5 (16/16) and VH15 (15 /16) than in group C (8/16) or VH5 (9/16), The recovery of adenosine tripho sphate in liver tissue was faster, and the release of liver-related enzymes during reperfusion was lower in groups GH5 and VH15 than in group C or VH5 . Administration of GGA before heat shock preconditioning augmented the ind uction of HSP72 by decreasing the threshold for triggering the stress respo nse.