Protein-deficient pigs cannot maintain reduced glutathione homeostasis when subjected to the stress of inflammation

The mechanisms responsible for depletion of systemic glutathione levels in nutritional deprivation and/or in infective and inflammatory conditions have not been fully established. We quantified the effects of protein undernutrition and experimental inflammation on the concentration and synthesis of reduced glutathione in the erythrocytes, liver and jejunal mucosa of young pigs. Two groups of five piglets consumed diets containing either 23 or 3% protein and, after 4 wk, were infused intravenously with [13C2]glycine before and 48 h after subcutaneous injections of turpentine. Erythrocyte, hepatic and intestinal mucosal reduced glutathione was quantified as the monobromobimane derivative by HPLC. Reduced glutathione synthesis was determined by measurements of the tracer/tracee ratio of reduced glutathione-bound glycine. In well-nourished piglets, turpentine injection had no effect on erythrocyte reduced glutathione concentrations or rate of synthesis. Protein undernutrition was associated with lower erythrocyte reduced glutathione concentrations (1.05 +/- 0.04 vs. 1.32 +/- 0.06 mmol/L, P < 0.01) and synthesis (42 +/- 5 vs. 60 +/- 5%/d), and turpentine inflammation caused a further fall in erythrocyte reduced glutathione concentration to 0.96 +/- 0.05 mmol/L, despite a significant (P < 0.05) increase in reduced glutathione synthesis. The combination of protein undernutrition and inflammation had a marked effect on mucosal reduced glutathione concentration (37 +/- 3% of control) and synthesis (65 +/- 5% of control). Hepatic reduced glutathione concentration and synthesis did not differ in the two groups. We conclude that the biosynthetic supply of reduced glutathione is sufficient to withstand an inflammatory challenge in well-nourished piglets but not in protein-deficient animals.