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Protein-Deficient Pigs Cannot Maintain Reduced Glutathione Homeostasis When Subjected to the Stress of Inflammation^1,2,

USDA/Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030

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.

KEY WORDS: • glutathione synthesis • stable isotope • protein deficiency • turpentine inflammation • pigs

¹ Supported by federal funds from the U.S. Department of Agriculture, Agricultural Research Service under cooperative agreement number 58-6250-1-003 and by National Institutes of Health grant DK41764. This is a publication of the U.S. Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX. The contents of this publication do not necessarily reflect the views or policies of the U.S. Department of Agriculture, nor does mention of trade names, commercial products or organizations imply endorsement by the United States government.

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ To whom correspondence should be addressed.

Manuscript received 18 October 1994. Revision accepted 24 January 1995.

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