The Organo- and Cytoprotective Effects of Heat-shock Protein in Response to Injury Due to Radiofrequency Ablation in Rat Liver

Anticancer Res. 2016 Jul;36(7):3591-7.

Abstract

Aim: In treating liver tumors, preserving hepatic reserve and reducing surgical invasiveness are important for minimizing postoperative complications. Geranylgeranylacetone (GGA) is reported to selectively induce heat-shock protein 70 (HSP70), which initiates a powerful cytoprotective effect. We investigated the function of HSP70 under conditions of radiofrequency ablation (RFA) of the liver.

Materials and methods: Male Wistar rats were divided into three groups: a control group, a group administered GGA, and a group administered GGA plus quercetin, an HSP70 synthesis inhibitor. Expression of HSP70 and heat-shock factor-1 (HSF1) in the liver was measured at the protein level, and severity of liver damage was investigated using serum and hepatic tissue.

Results: The GGA-treated group had higher expression of HSP70 and HSF1 than the other groups. Peak liver damage in all groups occurred 6 h after RFA. The GGA-treated group also had significantly less liver damage and lower serum level of the inflammatory cytokine tumor necrosis factor-α, and a lower rate of apoptosis in tissue around post-ablation necrosis. Expression of HSP70 and HSF1 was suppressed in the group treated with GGA and quercetin, and this group had severe liver damage.

Conclusion: Induction of HSP in the liver by GGA may be applicable in future treatments for hepatocellular carcinoma or liver metastasis. The present findings suggest that if preoperative administration of GGA can offer protective effects in the liver, treatment options could be increased and liver failure and other complications might be avoided.

Keywords: Heat-shock protein; geranylgeranylacetone; radiofrequency ablation.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • DNA-Binding Proteins / metabolism
  • Diterpenes / pharmacology
  • HSP70 Heat-Shock Proteins / metabolism*
  • Heat Shock Transcription Factors
  • Liver / metabolism*
  • Liver / pathology
  • Liver / radiation effects
  • Male
  • Protective Factors
  • Quercetin / pharmacology
  • Radiation Injuries, Experimental / metabolism*
  • Radiosurgery / adverse effects*
  • Rats, Wistar
  • Transcription Factors / metabolism

Substances

  • Antioxidants
  • DNA-Binding Proteins
  • Diterpenes
  • HSP70 Heat-Shock Proteins
  • Heat Shock Transcription Factors
  • Hsf1 protein, rat
  • Transcription Factors
  • Quercetin
  • geranylgeranylacetone