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Geranylgeranylacetone Prevents Acute Liver Damage after Massive Hepatectomy in Rats through Suppression of a CXC Chemokine GRO1 and Induction of Heat Shock Proteins

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Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background and Methods

Acute liver failure after massive hepatectomy remains a challenging problem. In this study, using a microarray designed to monitor the side effects of drugs, we examined changes in gene expression in the remnant liver during the 24 h after hepatectomy and the effects of a nontoxic heat shock protein (HSP) 70 inducer, geranylgeranylacetone (GGA), after 90% hepatectomy in rats.

Results

A single oral administration of 100 mg/kg GGA significantly suppressed the release of aminotransferases and improved survival compared with vehicle administration. The hepatectomy upregulated 74 genes and downregulated 95. Interestingly, ten cytokine genes were upregulated, while no cytokine-related gene was downregulated. Among the ten cytokine genes, a potent chemoattractant for neutrophils, GRO1, was most rapidly and markedly upregulated after 90% hepatectomy. GGA effectively suppressed the up-regulation of GRO1 messenger ribonucleic acid, and this was validated by Northern hybridization. Microarray and immunoblot analyses showed that, in addition to HSP70 and HSP27, GGA preferentially induced an endoplasmic reticulum chaperone, BIP.

Conclusion

Considering hemodynamic and metabolic overloading as a primary cause of acute lever failure, the ER stress response enhanced by GGA may also play an important role in the prevention of overload-induced liver damage.

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Authors and Affiliations

  1. Department of Digestive and Pediatric Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan

    Hirofumi Kanemura, Hidenori Miyake, Seiki Tashiro & Mitsuo Shimada

  2. Department of Stress Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, 770-8503, Japan

    Kenji Kusumoto & Kazuhito Rokutan

Authors
  1. Hirofumi Kanemura
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  2. Kenji Kusumoto
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  3. Hidenori Miyake
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  4. Seiki Tashiro
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  6. Mitsuo Shimada
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Correspondence to Mitsuo Shimada.

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Kanemura, H., Kusumoto, K., Miyake, H. et al. Geranylgeranylacetone Prevents Acute Liver Damage after Massive Hepatectomy in Rats through Suppression of a CXC Chemokine GRO1 and Induction of Heat Shock Proteins. J Gastrointest Surg 13, 66–73 (2009). https://doi.org/10.1007/s11605-008-0604-x

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  • DOI: https://doi.org/10.1007/s11605-008-0604-x

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