Effect of fasting on the lung glutathione redox cycle in air- and oxygen-exposed mice: beneficial effects of sugar.
Fasting increases susceptibility to hyperoxic lung damage in mice, at least in part, by decreasing lung glutathione level. To determine whether fasting alters other components of the glutathione redox cycle, and whether a diet of sugar alone reverses fasting's effects, normally fed, sugar-fed, and fasted mice were exposed to room air or 100% oxygen for up to 4 days. In air-exposed mice, fasting decreased glutathione peroxidase (GP) and glutathione reductase (GR) activities 15% to 20% on days 3 and 4 (p less than 0.01) and glutathione level 25% to 30% on days 2 to 4 (p less than 0.05). When corrected for protein concentration, GP and GR values were similar to those in the fed mice, but glutathione levels remained lower on days 2 and 3 (p less than 0.05). Oxidized glutathione (GSSG) was unchanged, but the ratio of GSSG to total glutathione (reduced glutathione plus GSSG) increased on day 2 (p less than 0.05). In oxygen-exposed fed mice, GP increased 62% and GR increased 39% on day 4 (p less than 0.05), the time when the lung injury was most severe; glutathione increased 30% on days 3 and 4 (p less than 0.05); and GSSG increased threefold and eightfold on days 3 and 4 (p less than 0.01). Oxygen-exposed fasted mice were all dead by day 3 (versus no deaths in the fed mice), failed to increase GR and total glutathione in response to the oxidant stress, and increased GP and GSSG on day 3 to the same extent as the fed mice did on day 4.(ABSTRACT TRUNCATED AT 250 WORDS)