Geranylgeranylacetone suppresses inflammatory responses and improves survival after massive hepatectomy in rats

Hironobu Oda, Hidenori Miyake, Takashi Iwata, Kenji Kusumoto, Kazuhito Rokutan, Seiki Tashiro, K. Behrns, E. Klar, Henry A. Pitt

Research output: Contribution to journalArticle

Abstract

Overproduction of heat shock protein 70 (HSP70) in the liver protects hepatocytes under various pathologic conditions. In this study we examined the effects of a nontoxic HSP70 inducer, geranylgeranylacetone (GGA), on acute hepatic failure after 95% hepatectomy in rats. When GGA (100 mg/kg) or vehicle was intragastrically administered to rats 4 hours before 95% hepatectomy, all 25 rats pretreated with vehicle died within 60 hours after the operation, whereas 10 of 25 rats pretreated with GGA survived. During the 24-hour postoperative period, GGA significantly suppressed the release of aspartate or alanine aminotransferase and elevation of the serum interleukin-6 level, and completely inhibited an increase in the serum level of tumor necrosis factor-alpha. Histologic examinations showed that GGA prevented hemorrhagic necrosis, which was observed in vehicle-treated livers more than 12 hours after the operation. During the 24-hour postoperative period, HSP70 induction was absent in remnant livers of vehicle-treated rats. In contrast, GGA stimulated the HSP70 mRNA expression and HSP70 accumulation within 4 hours, and viable hepatocytes contained abundant HSP70 in their nuclei. Our results suggest that GGA may prevent acute liver failure after massive hepatectomy, at least in part, by enhancing HSP70 induction in the remnant liver.

Original languageEnglish (US)
Pages (from-to)464-473
Number of pages10
JournalJournal of Gastrointestinal Surgery
Volume6
Issue number3
DOIs
StatePublished - Dec 1 2002

Keywords

  • Geranylgeranylacetone
  • Heat shock protein 70
  • Liver failure
  • Massive hepatectomy

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology

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