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. Materials and 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 8C). 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 8C progressively impaired oxidative phosphorylation in isolated mitochondria. Significant inhibition of the respiratory chain components was observed after perfusion at 42 8C, irreversible uncoupling became evident after liver perfusion at higher temperatures (46 8C and above). After perfusion at 50–52 8C 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. [...]