Effect of fasting on the lung glutathione redox cycle in air- and oxygen-exposed mice: Beneficial effects of sugar

Lewis J Smith*, P. Horcher, J. Anderson, M. Shamsuddin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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 < 0.01) and glutathione level 25% to 30% on days 2 to 4 (p < 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 < 0.05). Oxidized glutathione (GSSG) was unchanged, but the ratio of GSSG to total glutathione (reduced glutathione plus GSSG) increased on day 2 (p < 0.05). In oxygen-exposed fed mice, GP increased 62% and GR increased 39% on day 4 (p < 0.05), the time when the lung injury was most severe; glutathione increased 30% on days 3 and 4 (p < 0.05); and GSSG increased threefold and eightfold on days 3 and 4 (p < 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. Sugar-fed mice exposed to air had no change in GP, GR, total glutathione, or GSSG. When these mice were exposed to oxygen, the results were nearly identical to those seen in normally fed mice including significantly lower mortality than in the fasted mice on day 3 (25% vs 100%). Although the sugar-fed mice consumed no protein, they maintained nearly normal levels of total glutathione during air exposure and were able to increase total glutathione and GR appropriately during oxygen exposure. These results suggest that fasting increases susceptibility to hyperoxic lung damage by its effects on both total glutathione and GR. In this system, short-term protein and fat deprivation, in the setting of adequate carbohydrate calories, does not have a major effect on the glutathione redox cycle or increase susceptibility to hyperoxic lung damage.

Original languageEnglish (US)
Pages (from-to)717-723
Number of pages7
JournalJournal of Laboratory and Clinical Medicine
Volume116
Issue number5
StatePublished - Jan 1 1990

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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