ENERGETIC AND ANTIOXIDANT STATUS OF RAT LIVER MITOCHONDRIA DURING HYPOXIA-REOXYGENATION OF DIFFERENT DURATION

Abstract

Dynamics of changes in activity and protein expression of antiradical (MnSOD), glutathione-dependent (glutathione peroxidase, glutathione reductase) and NADP⁺-generated (isocitrate dehydrogenase) enzymes as well as in the energy metabolism indeces in rat liver mitochondria under hypoxia- reoxygenation of different duration (1, 3, 7 14 days) were studied. Prolonged hypoxia-reoxygenation was characterized by phase changes of the corticosterone concentration in rat blood, which corresponded to the changes in energy metabolism as well as in pro- and antioxidant balance in rat liver mitochondria. It has been shown that short-term (1 day) hypoxia-reoxygenation (5% O2 in the gas mixture) led to an increase in the blood corticosterone concentration and a significant activation of oxidative processes and energy metabolism in rat liver mitochondria, the intensity of which was reduced to 3rd day. Long- term hypoxia--reoxygenation (7-14th days) led to the gradual depletion of the organism adaptive capabilities, as evidenced by a significant decline in the blood corticosterone concentration, an increase in the content of secondary products of lipid peroxidation, an imbalance in pro- and antioxidant reactions and reduction of energy capacity in liver cells mitochondria. It has been shown that the glutathione peroxidase protein expression and enzymatic activity increased constantly during the whole experimental period and correlated positively with the level of H₂O₂. The amount of Mn-SOD protein as well as it's enzymatic activity was lower in the first seven days of experiment, and it was increased in consequent days up to the control level on 14thday. Increased activity of glutathione peroxidase, glutathione reductase and NADP+⁺dependent isocitrate dehydrogenase during prolonged hypoxia - eoxygenation indicates that glutathione- and NADPH-generating enzymes, were actively involved in the antioxidant protect.