Mechanism of induction of oxidative stress in liver mitochondria by low concentrations of tert-butyl hydroperoxide

• Published in: Biochemistry (Moscow) 2013, Vol.78 (1), p.75-79
• Main Authors: Fedotcheva, N. I., Mokhova, E. N.
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Biophysics; Calcium Chloride - pharmacology; Care and treatment; Causes of; Chemical properties; Cyclosporine; Cyclosporine - pharmacology; Dose-Response Relationship, Drug; Electric potential; Hemochromatosis; Kinetics; Life Sciences; Liver; Male; Microbiology; Mitochondria; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Oxidative stress; Oxidative Stress - drug effects; Physiological aspects; Properties; Pyruvates; Rats; Rats, Wistar; tert-Butylhydroperoxide - antagonists & inhibitors; tert-Butylhydroperoxide - pharmacology; Tertiary butyl hydroperoxide; Vitamin C
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1134/S0006297913010094

The mechanism of the effect of tert -butyl hydroperoxide (tBHP) on the kinetics of decrease in liver mitochondrial ΔΨ (transmembrane electric potential) in response to successive additions of tBHP in low concentrations has been studied. FeSO 4 was found to increase significantly the damaging effect of tBHP; this effect was shown to increase in the presence of low concentrations of Ca 2+ starting from 2 μM CaCl 2 . Cyclosporin A prevents these effects. The data show that the damaging effect of low concentrations of tBHP in the course of pyruvate oxidation in isolated liver mitochondria is caused by the opening of the nonspecific Ca 2+ -dependent cyclosporin A-sensitive pore in the inner mitochondrial membrane. Application of a method of studying oxidative stress regulators, developed in this work, is illustrated by an example of the prooxidant action of ascorbate. This method is proposed for studying mitochondria in hemochromatosis, a pathology caused by excessive accumulation of iron.