Glutathione localization and distribution after intratracheal instillation. Implications for treatment.

To gain insight into how glutathione given directly into the lung protects fasted mice against hyperoxic lung damage and to provide a framework for developing treatment strategies in patients, we determined the lung distribution and retention of intratracheally administered glutathione (GSH) and its fate after leaving the lung. Mice received an intratracheal injection of [3H]GSH with or without cold GSH and with or without liposomes. The distribution of the 3H label was equal in both lungs, but the left lung had a higher concentration because of its smaller size. The 3H label was cleared rapidly from the lung: only 1% remained at 24 h, and more than 50% of the label at that time was no longer attached to the GSH. Administration of GSH with liposomes increased the retention of GSH by 20 to 50%, but the amount remaining at 24 h was still only 1%. The increase associated with the liposomes was due to enhanced retention of the GSH encapsulated in the liposomes, not the much larger amount present free in the GSH-liposome mixture. Fasting and exposure to 100% oxygen had little effect on GSH retention. Some of the 3H label leaving the lung was excreted by the kidneys, a small amount was retained in the liver, and a large amount accumulated in the blood. Of the amount in the blood, about 60% was in red blood cells (RBC) and the rest in plasma. Much of the 3H label in RBC and lung at 24 h was no longer attached to the GSH, whereas most in the plasma and liver was.(ABSTRACT TRUNCATED AT 250 WORDS)