Oxygen effects of metabolism and paraquat uptake in rat lung slices

Paraquat accumulation into rat lung slices was unaffected by hypoxia (PO2 = 645 mm Hg) but was inhibited by hypoxia. The IC50 (IC50 = partial pressure of O2 resulting in a 50% inhibition of paraquat accumulation) for paraquat accumulation was P02 = 50 mm Hg; significant accumulation could be observed after 1 or 2 hr of incubation at PO2 = 10 mm Hg. The hypoxic inhibition was due to oxygen limitation of the accumulation mechanism and not to a diffusion limitation of oxygen or to cell death. Incubation of lung slices for up to 2 hr in 100% N2 (PO2 = 0 mm Hg) did not decrease paraquat accumulation or metabolism of glucose to CO2 when the slices were returned to room air. However, under the same conditions total tissue oxygen consumption was decreased by 50%. Paraquat accumulation and glucose metabolism are oxygen dependent but are resistant to the damaging effects of cellular anoxia.