title: Efficacy of HSP72 induction in rat liver by orally administered geranylgeranylacetone.
abstract: It is well known that heat-shock proteins (HSPs) have a cytoprotective function as "molecular chaperones" when cells are exposed to several stress conditions. Geranylgeranylacetone (GGA) is an antiulcer drug that was developed in Japan and it has recently been reported to induce HSP72 in rat gastric mucosa. In this experiment, we investigated the induction of HSP72 in rat liver in response to oral administration of GGA and assessed its ability to induce tolerance to warm ischemic injury by this approach. We prepared donor rats by orally administering GGA to them and compared HSP72 expression in graft liver, survival rates, and serum TNF-alpha concentrations after liver transplantation with the findings in controls. The survival rates were significantly increased when the livers were obtained from donor rats given GGA. Western blotting revealed expression of HSP72 in graft livers given GGA, and the serum TNF-alpha levels were significantly suppressed in the rats given GGA. Oral administration of GGA induced HSP72 in graft livers, and they were better able to tolerate warm ischemic injury. Oral administration of GGA appears to provide a promising new strategy for preventing ischemia-reperfusion injury.
authors: Second Department of Surgery, Hiroshima University, Faculty of Medicine, Japan. y-fudaba@mwe.biglobe.ne.jp
authors: Y
authors: Y
authors: Fudaba
authors: H
authors: H
authors: Tashiro
authors: H
authors: H
authors: Ohdan
authors: Y
authors: Y
authors: Miyata
authors: S
authors: S
authors: Shibata
authors: S
authors: S
authors: Shintaku
authors: M
authors: M
authors: Nishihara
authors: T
authors: T
authors: Asahara
authors: H
authors: H
authors: Ito
authors: Y
authors: Y
authors: Fukuda
authors: K
authors: K
authors: Dohi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D006085:Graft Survival; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D007511:Ischemia; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D016031:Liver Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D009926:Organ Preservation / Q000379:methods; D051381:Rats; D011914:Rats, Inbred BN; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
chemical_list: D004224:Diterpenes; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D014409:Tumor Necrosis Factor-alpha; C031049:geranylgeranylacetone