Inhibition of rabbit lung glucose-6-phosphate dehydrogenase by dehydroepiandrosterone augments oxidant injury.

The contribution of lung glucose-6-phosphate dehydrogenase (G-6-PD) activity to pulmonary antioxidant defenses was investigated in the isolated perfused rabbit lung using dehydroepiandrosterone (DHEA), a specific steroidal inhibitor of G-6-PD. Infusion of xanthine oxidase (0.002 U/ml) generated moderate lung edema as measured by increased lung weight and lung lavage albumin content. Infusion of DHEA caused an augmentation of xanthine oxidase-induced lung edema. Hydrostatic factors did not participate in the worsened lung edema because mean pulmonary artery pressures were similar in both experimental groups. Incubation of lung tissue in vitro with DHEA demonstrated ablation of tissue G-6-PD activity without decreasing catalase, glutathione peroxidase, or superoxide dismutase activity. It was concluded that DHEA is a specific inhibitor of lung G-6-PD, and that G-6-PD provides an important antioxidant defense mechanism in preventing oxidant-induced lung injury.