Effects of long-term oxygen treatment on alpha-ketoglutarate dehydrogenase activity and oxidative modifications in mitochondria of the guinea pig heart

Oxygen therapy is used for the treatment of various diseases, but prolonged exposure to high concentrations of O(2) is also associated with formation of free radicals and oxidative damage. In the present study we compared alpha-ketoglutarate dehydrogenase (KGDH) activity and mitochondrial oxidative damage in the hearts of guinea pigs after long-term (17 and 60 h) oxygenation with 100% normobaric O(2) and with partially negatively (O(2 neg)) or positively (O(2 posit)) ionized oxygen. Inhalation of O(2) led to significant loss in KGDH activity and thiol group content and accumulation of bityrosines. Inhalation of O(2 neg) was accompanied by more pronounced KGDH inhibition, possibly due to additional formation of protein-lipid conjugates. In contrast, O(2 posit) prevented loss in KGDH activity and diminished mitochondrial oxidative damage. These findings suggest that oxygen treatment is associated with impairment of heart energy metabolism and support the view that inhalation of O(2 posit) optimizes the beneficial effects of oxygen therapy.