OXIDATIVE FUNCTION OF RAT LIVER MITOCHONDRIA DURING ACUTE HYPEROXIA AND RECOVERY
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Abstract
Energy metabolism in the liver, a key organ regulating both substance and energy metabolism in the body, depends critically on oxygen consumption. The primary organelles responsible for oxidative energy metabolism are mitochondria. Hyperoxia and oxygen therapy are widely used as therapeutic interventions in hepatic diseases and metabolic disorders. However, the specific effects of hyperoxia on energy metabolism and the oxidative function of liver mitochondria remain insufficiently understood.
Purpose. The aim of this study was to investigate the oxidative function of rat liver mitochondria under different types of hyperoxic exposure.
Methods. The oxidative function of mitochondria was examined in 35 male Wistar rats. The polarographic method described by Chance and Williams was used. Mitochondrial respiration was assessed in liver homogenates using an open platinum electrode and a thermostabilized chamber containing the incubation medium and oxidation substrates. The oxygen consumption rate was measured under conditions of resting respiration (V4S), active respiration (V3), and controlled respiration (V4ATP) immediately after exposure to hyperoxia, as well as on days 1, 3, 5, 7, and 14 post-exposure. Respiration was stimulated by the addition of 200 μmol/L ADP. The respiratory control ratio (V3/V4ATP) and the phosphorylation efficiency (ADP/O ratio) were calculated.
Results. Under hyperoxic conditions, the rate of active respiration (V3) significantly increased during the oxidation of FAD-dependent succinate, but not during the oxidation of the NAD-dependent glutamate + malate mixture. The efficiency of oxidation and phosphorylation was restored by day 7 after hyperoxic exposure when electron transport chain Complex II was involved, whereas with Complex I substrates, it remained below baseline for 14 days. A significant increase in mitochondrial energization was observed from day 5 onward during the oxidation of NAD-dependent substrates compared to the immediate post-exposure level.
Originality. This study demonstrates for the first time that hyperoxia-induced alterations in liver mitochondrial oxidative function occur in a phase-dependent manner.
Conclusions. During hyperoxia, mitochondrial respiration is activated through electron transport chain Complex II, while the activity of Complex I is suppressed. It is proposed that Complex II contributes to the adaptive response of mitochondrial respiration to hyperoxic exposure.
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