PREVENTION OF INTRACELLULAR ADENOSINE-TRIPHOSPHATE DEPLETION AFTER SUBLETHAL OXIDANT INJURY TO RAT TYPE-II ALVEOLAR EPITHELIAL-CELLS WITH EXOGENOUS GLUTATHIONE AND N-ACETYLCYSTEINE

The alveolar epithelial cells of the lower respiratory tract are expos ed continuously to injurious agents, including oxygen radicals. The ty pe II alveolar epithelial cell is critically important to the normal f unction of the lung, because it is responsible for synthesis of surfac tant and other essential duties. In the current investigation, the aut hors documented the loss of intracellular adenosine triphosphate (ATP) after exposure of the cells to sublethal concentrations of hydrogen p eroxide (H2O2) and hypochlorous acid, Subsequent experiments attempted to alleviate or prevent this oxidant mediated loss of ATP by preincub ating the cells with either glutathione or N-acetylcysteine (NAC). Ini tially, it was determined that exposure of the type II cells to 250 mu M hypochlorous acid or 250 mu M H2O2 for 1 hour each would cause sign ificant loss of type II cell ATP. However, preincubation with glutathi one (1,000 mu M) inhibited the loss of ATP after both exposure to 250 mu M H2O2 (24 +/- 3% loss of ATP without glutathione compared with 13 +/- 2% loss with glutathione, P < 0.05), and 250 mu M hypochlorous aci d (12 +/- 2% loss of ATP without glutathione compared with 1 +/- 1% in crease of ATP with glutathione). Similar results were obtained using N AC (2 mg/mL) after exposure to 250 mu M H2O2 (23 +/- 2% loss of ATP wi thout NAC compared with a 4 +/- 3% loss of ATP with NAC). This study d emonstrates that exogenous glutathione and NAC are able to protect typ e II cells from oxidant mediated sublethal injury and loss of intracel luIar ATP stores.