Significance of Heat Shock Protein 70 Expression Prior to Extensive Hepatectomy : Effect of Ischemic Preconditioning and Administration of Geranylgeranylacetone

Abstract

How heat shock protein (HSP) mitigate liver damage after extensive hepatectomy after ischemic preconditioning or administration of HSP inducer, geranylgeranylacetone (GGA) may be of clinical significance. The purpose of the present study was to evaluate the cytoprotective effect of preconditioning and administration of GGA, and to elucidate the cytoprotective mechanism of HSP70 from the standpoint of the activation of transcription factor NF-_kB. Materials and methods. Male Wistar rats were subjected to 90% extensive hepatectomy. The animals were divided into 3 groups. Group N were subjected to 90% hepatectomy. Group P were subjected to 30-minute liver ischemia as preconditioning 48 hours prior to 90% hepatectomy. Group G were given oral GGA in a dose of 200mg/ kg body weight for 7 days prior to 90% hepatectomy. Examined were survival rate, expression of HSP70 and NF-_kB (Western blot analysis), and apoptosis of remnant liver cells (DNA fragmentation assay). Results. The 7-day survival rate in group N, group P, and group G was 0%, 40%, and 62.5%, respectively. HSP70 expression in group P and group G was increased 5 fold and 7 fold, respectively, after 90% hepatectomy. Expression of NF-_kB p65 was significantly lower in groups P and G than in group N. The percentage DNA fragmentation was significantly higher in group N than in groups P and G. In conclusion, ischemic preconditioning and administration of GGA prior to extensive hepatectomy may alleviate liver cell damage by maintaining cell viability and regulation of apoptosis. The HSP70 may inhibit the expression of NF-_kB at the transcriptional level and overexpression of the inflammatory response.