Ascorbic acid and paraquat: Oxygen depletion with concurrent oxygen activation

Ascorbic acid and paraquat produce an efficient redox pair which will deplete oxygen from physiological buffer systems. This reaction is partially blocked by superoxide dismutase or catalase and is potentiated by the hydroxyl radical scavenger, dimethyl sulfoxide. Mitochondria isolated after incubation of rat lung slices with 1.0 mm paraquat and 10.0 mm ascorbate were unresponsive to ADP (were “uncoupled”). Also, metabolism of 1-¹⁴C]- and 6-¹⁴C]glucose was inhibited by 50% in lung slice preparations. These results suggest a synergistic interaction of ascorbate and paraquat which results in disruption of subcellular energy metabolism. Paraquat accumulation into lung slices, an active transport process of the pulmonary cell membrane, was also inhibited by the addition of ascorbate. These results suggest that the previously reported in vivo potentiation of paraquat toxicity by ascorbate may be related to either: (1) a decreased subcellular oxygen availability, or (2) the presence of activated oxygen species, or (3) both.