title: Contribution of mitochondria to injury of hepatocytes and liver tissue by hyperthermia.
abstract: OBJECTIVE
  The aim of this study was to investigate functional changes of liver mitochondria within the experimentally modeled transition zone of radiofrequency ablation and to estimate possible contribution of these changes to the energy status of liver cells and the whole tissue.
  
  
  METHODS
  Experiments were carried out on mitochondria isolated from the perfused liver and isolated hepatocytes of male Wistar rats. Hyperthermia was induced by changing the temperature of perfusion medium in the range characteristic for the transition zone (38-52°C). After 15-min perfusion, mitochondria were isolated to investigate changes in the respiration rates and the membrane potential. Adenine nucleotides extracted from isolated hepatocytes and perfused liver subjected to hyperthermic treatment were analyzed by HPLC.
  
  
  RESULTS
  Hyperthermic liver perfusion at 42-52°C progressively impaired oxidative phosphorylation in isolated mitochondria. Significant inhibition of the respiratory chain components was observed after perfusion at 42°C, irreversible uncoupling became evident after liver perfusion at higher temperatures (46°C and above). After perfusion at 50-52°C energy supplying function of mitochondria was entirely compromised, and mitochondria turned to energy consumers. Hyperthermia-induced changes in mitochondrial function correlated well with changes in the energy status and viability of isolated hepatocytes, but not with the changes in the energy status of the whole liver tissue.
  
  
  CONCLUSIONS
  In this study the pattern of the adverse changes in mitochondrial functions that are progressing with increase in liver perfusion temperature was established. Results of experiments on isolated mitochondria and isolated hepatocytes indicate that hyperthermic treatment significantly and irreversibly inhibits energy-supplying function of mitochondria under conditions similar to those existing in the radiofrequency ablation transition zone and these changes can lead to death of hepatocytes. However, it was not possible to estimate contribution of mitochondrial injury to liver tissue energy status by estimating only hyperthermia-induced changes in adenine nucleotide amounts on the whole tissue level.
authors.affiliation: Faculty of Natural Sciences, Vytautas Magnus University, Kaunas, Lithuania.
authors.forename: Rasa
authors.initials: R
authors.lastname: Žūkienė
authors.affiliation: Faculty of Natural Sciences, Vytautas Magnus University, Kaunas, Lithuania.
authors.forename: Zita
authors.initials: Z
authors.lastname: Naučienė
authors.affiliation: Faculty of Natural Sciences, Vytautas Magnus University, Kaunas, Lithuania.
authors.forename: Giedrė
authors.initials: G
authors.lastname: Šilkūnienė
authors.affiliation: Department of Surgery, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Tomas
authors.initials: T
authors.lastname: Vanagas
authors.affiliation: Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Antanas
authors.initials: A
authors.lastname: Gulbinas
authors.affiliation: Institute of Biosciences, Vilnius University Life Sciences Center, Vilnius, Lithuania.
authors.forename: Aurelijus
authors.initials: A
authors.lastname: Zimkus
authors.affiliation: Faculty of Natural Sciences, Vytautas Magnus University, Kaunas, Lithuania. Electronic address: vida.mildaziene@vdu.lt.
authors.forename: Vida
authors.initials: V
authors.lastname: Mildažienė
mesh_terms: D000227:Adenine Nucleotides / Q000032:analysis; D000818:Animals; D017209:Apoptosis; D017115:Catheter Ablation / Q000009:adverse effects*; D002470:Cell Survival; D002851:Chromatography, High Pressure Liquid; D022781:Hepatocytes / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D006358:Hot Temperature / Q000009:adverse effects*; D008099:Liver / Q000293:injuries*; D008297:Male; D008930:Mitochondria, Liver / Q000502:physiology* / Q000648:ultrastructure; D010085:Oxidative Phosphorylation; D010477:Perfusion / Q000009:adverse effects; D061251:Primary Cell Culture; D051381:Rats; D017208:Rats, Wistar; D044366:Transition Temperature
chemical_list: D000227:Adenine Nucleotides
keywords: Apoptosis; Hepatocytes; Hyperthermia; Mitochondria; Oxidative phosphorylation