Mitochondrial Membrane Barrier Function as a Target of Hyperthermia

Zita Naučienė, Rasa Žūkienė, Laima Degutytė-Fomins, Vida Mildažienė

Department of Biochemistry and Biotechnologies, Faculty of Natural Sciences, Vytautas Magnus University, Lithuania

Key words: mitochondria; membrane permeability; hyperthermia; hyperthermic perfusion; modular kinetic analysis.

Summary. Background and Objective. Hyperthermia is a promising modality for cancer treatment that urgently requires detailed knowledge on molecular and cellular processes for the rational development of treatment protocols. The thorough study of the response of the inner membrane of heart and liver mitochondria to hyperthermia was performed in order to establish the pattern of the hyperthermia-induced changes in the membrane barrier function.

Material and Methods. The isolated mitochondria from rat heart and liver (of both genders) were used for experiments, as well as mitochondria isolated from the perfused male rat liver. Changes in the membrane permeability were evaluated by mitochondrial respiration in state 2 or by estimation of the modular kinetics of the membrane leak.

Results. The inner membrane of isolated mitochondria from healthy tissues was found to be an extremely sensitive target of hyperthermia that exerted the response even in the febrile range. More severe hyperthermia compromised the inner mitochondrial membrane function; however, this response was tissue-specific and, to some extent, gender-dependent (for liver mitochondria). The data obtained by direct heating of isolated mitochondria were validated by experiments on the perfused liver.

Conclusions. The obtained results imply a crucial importance of the evaluation of the tissue- and gender-specific differences while developing or improving the protocols for hyperthermic treatment or combinatory therapy.

Correspondence to V. Mildažienė, Department of Biochemistry and Biotechnologies, Faculty of Natural Sciences, Vytautas Magnus University, Vileikos 8, 44404 Kaunas, Lithuania. E-mail: v.mildaziene@bs.vdu.lt

Received 20 March 2012, accepted 31 May 2012